Upcoming

All upcoming events

CNIO - MICC Joint Conference on Cancer Research

Date:
03
Tuesday
September
2019
-
05
Thursday
September
2019
Conference
Time: 08:00
Location: David Lopatie Conference Centre
Organizer: The Moross Integrated Cancer Center (MICC)

The Long and Winding Road: From HIV Reverse Transcriptase Structure to Five Therapeutic Drugs, and New Insights into Viral Assembly and Maturation

Date:
22
Sunday
September
2019
Lecture / Seminar
Time: 14:00-15:00
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Eddy Arnold
Organizer: Department of Structural Biology

Ribosomal decoding, tRNA modifications and human disease

Date:
23
Monday
September
2019
Colloquium
Time: 11:00-12:15
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Eric Westhof
Organizer: Faculty of Chemistry
Abstract: Decoding during ribosomal translation occurs through complex and interdependent ...Decoding during ribosomal translation occurs through complex and interdependent molecular recognition networks between mRNA, tRNA, and rRNA. Among those, the stability of codon-anticodon triplets, the fold of the tRNA anticodon hairpin, the modified nucleotides, and the interactions with rRNA bases at the decoding site cosntitute key contributors. On the basis of biochemical and genetic data in the literature, coupled with many crystal structures of fully active ribosomes, nucleotide modifications at positions 34 and 37 of the anticodon loop are now understood molecularly. Both pre-organize the anticodon loop for efficient mRNA binding. The modifications at 37 stabilize AU-rich codon-anticodon pairs and maintain the coding frame. The modifications at 34 help to avoid miscoding and allow to decode purine-ending codons in split codon boxes by promoting base pairing that can be accommodated within the structural constraints of the ribosomal grip at the decoding site. Depending on the codon box, the tRNA modifications allow for diversity in codon usage depending on genomic GC content as well as on the number and types of isoacceptor tRNAs. Although universal, the genetic code is not translated identically and differences exist not only between organisms in the three kingdoms of life but also between cellular types. To decipher diversely but efficiently the genetic code, cells developed sophisticated arrays between tRNA pools and tRNA modifications, anchored in the cellular metabolic enzymatic pathways and guaranteeing protein homeostasis. Examples of mutations leading to specific human diseases in some of those enzymes will be described.

Advanced Practical Workshop in Drug Discovery

Date:
28
Monday
October
2019
-
31
Thursday
October
2019
Conference
Time: 08:00
Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
Organizer: G-INCPM

Ovarian Cancer: From Bench To Bedside

Date:
21
Tuesday
January
2020
-
23
Thursday
January
2020
Conference
Time: 08:00
Location: David Lopatie Conference Centre
Organizer: Dwek Institute for Cancer Therapy Research

Cancer Metabolism and Immunity

Date:
05
Tuesday
May
2020
-
07
Thursday
May
2020
Conference
Time: 08:00
Location: David Lopatie Conference Centre

Chemical Biology Conference

Date:
17
Sunday
May
2020
-
19
Tuesday
May
2020
Conference
Time: 08:00
Location: David Lopatie Conference Centre

From personalized human genomes to immune system variation- the 27th Pasteur-Weizmann Symposium

Date:
30
Monday
November
2020
-
02
Wednesday
December
2020
Conference
Time: 08:00
Location: David Lopatie Conference Centre

    Past

    All Events

    A Moving Target: Tracking Cancer Plasticity in Cells and in Patients

    Date:
    25
    Thursday
    July
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Amir Goldkorn
    Organizer: Department of Biological Regulation

    An update on anti-TB drug discovery program against multi-drug resistant Tuberculosis

    Date:
    21
    Sunday
    July
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Prof. V. Samuel Raj
    Organizer: Department of Structural Biology

    Trio correlation between cell mechanics, phagocytic capacity, and cancer aggressiveness

    Date:
    14
    Sunday
    July
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Ofra Benny
    Organizer: Department of Materials and Interfaces
    Abstract: A comprehensive study showing a trio correlation between cell mechanics, phagocy ...A comprehensive study showing a trio correlation between cell mechanics, phagocytic capacity, and cancer aggressiveness is presented. Mechanical properties of particles are shown to have a critical effect on the interactions with malignant cancer cells. Our findings offers new directions for mechanical based specificity in cancer treatment, and could lead to uptake measurement as a diagnostic tools for precision medicine.

    Natural Killer Cell Therapy: From Hematopoietic stem cells to NK cells

    Date:
    11
    Thursday
    July
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Inpyo Choi
    Organizer: Department of Biological Regulation

    Automated optimisation of antibody variable fragments directly from sequence.

    Date:
    02
    Tuesday
    July
    2019
    Lecture / Seminar
    Time: 10:30-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Jake Parker
    Organizer: Department of Biomolecular Sciences
    Abstract: Antibodies are a family of vertebrate proteins capable of selective recognition ...Antibodies are a family of vertebrate proteins capable of selective recognition of almost any epitope, making them of great interest in biotechnological and therapeutic applications. However, many antibodies possess poor biophysical properties, leading to misfolding and aggregation, as well as unwanted non-specific interactions. In order increase the ease and speed with which an antibody can be optimised, and to solve issues associated with using single-chain antibody fragments (scFvs), we developed an automated pipeline for the re-engineering of antibody variable fragments directly from sequence.

    Probing the conformational behavior of the multidrug transporter MdfA during drug binding and transport.

    Date:
    02
    Tuesday
    July
    2019
    Lecture / Seminar
    Time: 10:00-10:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Eliane Yardeni
    Organizer: Department of Biomolecular Sciences
    Abstract: The E. coli secondary multidrug transporter, MdfA from the major facilitator sup ...The E. coli secondary multidrug transporter, MdfA from the major facilitator superfamily (MFS), uses the electrochemical potential to extrude a vast variety of dissimilar drugs from the cytoplasm. It was proposed that MdfA follows the alternating access model, in which its N- and C-terminal domains rock one against the other, exposing the drug binding site either towards the cytoplasm or the periplasm. In our study we aim to analyze the functional states of MdfA to better understand its conformational behavior during drug binding and transport. For this we used double electron-electron resonance and cysteine-cysteine crosslinking to probe intramolecular distances under different conditions, both in detergent micelles and in nanodiscs.

    Cytokines as neuromodulators: How immunity affects brain function

    Date:
    27
    Thursday
    June
    2019
    Lecture / Seminar
    Time: 14:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Jonathan Kipnis
    Organizer: Department of Neurobiology
    Details: Host: Prof. Michal Schwartz michal.schwartz@weizmann.ac.il tel: 6036 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: Immune cells and their derived molecules have major impact on brain function, bu ...Immune cells and their derived molecules have major impact on brain function, but despite the robust influence on brain function, peripheral immune cells are not found within the brain parenchyma, a fact that only adds more mystery into these enigmatic interactions between immunity and the brain. Our results suggest that meningeal space, surrounding the brain, is the site where CNS-associated immune activity takes place and through which it impacts brain function. Unique sub-types of immune cells within meningeal spaces are producing certain sets of cytokines that impact specific behaviors. Three main cytokines and their neuromodulatory functions will be discussed in social, learning and risk-taking behaviors.

    Prof. Huib Ovaa DUB-selective reagents

    Date:
    27
    Thursday
    June
    2019
    Lecture / Seminar
    Time: 14:00-15:30
    Title: Dr. Barry Sherman Medical Chemistry and Chemical Biology Seminar Series
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Huib Ovaa
    Organizer: Faculty of Biochemistry

    Developmental Club Series 2018-2019

    Date:
    26
    Wednesday
    June
    2019
    Lecture / Seminar
    Time: 10:00
    Title: “Functional characterization and therapeutic targeting of gene regulatory elements”
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Nadav Ahituv
    Organizer: Department of Molecular Genetics

    IMM Guest seminar- Prof. Ofer Mandelboim will lecture on "TIGIT and its cellular and bacterial ligands: novel checkpoints for cancer immune therapy."

    Date:
    24
    Monday
    June
    2019
    Lecture / Seminar
    Time: 13:00-14:00
    Location: Wolfson Building for Biological Research
    Lecturer: Prof. Ofer Mandelboim
    Organizer: Department of Immunology

    Virus Structure: How Structural Biology Can Inform Function and Therapy

    Date:
    24
    Monday
    June
    2019
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. David Stuart
    Organizer: Department of Structural Biology

    Strongly interacting phonons at finite temperature

    Date:
    23
    Sunday
    June
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Olle Hellman
    Organizer: Department of Materials and Interfaces
    Abstract: Thermal motions of atoms is an ever-present phenomenon in all of solid state phy ...Thermal motions of atoms is an ever-present phenomenon in all of solid state physics. Phonons, quanta of heat, is the quasiparticule used to describe thermal motion in solids. Under normal conditions phonons are the dominant mechanism that govern transport and the largest contribution to entropy. I want to understand how phonons evolve in time, temperature, and how they behave when they interact strongly with each other or other quasiparticles. The inherent disorder in thermal motions makes theoretical predictions challenging. I will present methodological developments in finite temperature first principles simulations, specifically targeting strongly anharmonic systems. The method employs model Hamiltonians that explicitly depend on temperature. I will present applications pertaining to thermal conductivity, inelastic neutron spectra and phase stabilities, reproducing non-trivial temperature dependencies.

    Cell Penetration and Membrane Fusion: Two Sides of the Same Coin

    Date:
    23
    Sunday
    June
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Pavel Jungwirth
    Organizer: Department of Materials and Interfaces
    Abstract: Cell penetrating peptides have a unique potential for targeted drug delivery. Wh ...Cell penetrating peptides have a unique potential for targeted drug delivery. While ATP-driven endocytosis is known to play a major role in their internalization, there has been also ample evidence for the importance of passive translocation for which the direct mechanism, where the peptide is thought to directly pass through the membrane via a temporary pore, has been widely advocated. In this talk, I will question this view and demonstrate that arginine-rich cell penetrating peptides can instead enter vesicles and cells by inducing multilamellarity and fusion, analogously to the action of calcium ions. Allolio C., Magarkar A., Jurkiewiczf P., Baxová K., Javanainen M., Mason P.E., Sachl R., Cebecauer M., Hof M., Horinek D., Heinz V., Rachel R., Zieglerg C.M., Schrofel A., Jungwirth P.: Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore. Proceedings of the National Academy of Sciences USA 115 (2018) 11923.

    G-INCPM Special Guest Seminar - Dr. Vaclav Navratil, CEO & CTO, DIANA Biotechnologies, s.r.o.

    Date:
    20
    Thursday
    June
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Title: "DIANA: new platform for protein detection and screening of protein ligands"
    Location: Max and Lillian Candiotty Building
    Organizer: Department of Life Sciences Core Facilities
    Abstract: Recently developed DIANA platform (DNA-linked Inhibitor ANtibody Assay) is suita ...Recently developed DIANA platform (DNA-linked Inhibitor ANtibody Assay) is suitable for both ultrasensitive protein detection in in vitro diagnostics and for enzyme inhibitor or protein ligand screening in drug discovery. As its name suggests, we originally designed DIANA to detect enzymes and its inhibitors, but we later showed that it is well suited also for detection of receptors and its ligands, to screen for protein-protein interaction inhibitors and for detection of small molecules. DIANA overcomes the limitations of current state of the art methods, as it can detect zeptomole amounts of targets, has a linear range of up to six logs and is applicable to biological matrices. Screening of chemical libraries is an important step in drug discovery, but it remains challenging for targets, which are difficult to express and purify, and current methods tend to produce false results. The sensitivity and selectivity of DIANA enables quantitative high-throughput screening of enzyme inhibitors, receptor ligands or inhibitors of protein-protein interactions with unpurified proteins. DIANA addresses also the remaining limitations of the current screening methods, as it allows high-throughput screening with high signal-to-noise ratio (Z’ factor > 0.9), sensitive hit discovery and ultralow rate of false positives (< 0.02%); while quantitatively determining the inhibition potency from a single well and requiring only picogram to nanogram quantities of potentially unpurified protein target (e.g. in human serum). At DIANA Biotechnologies, a recently established spin-off from the Institute of Organic Chemistry and Biochemistry in Prague, we aim to fully exploit the potential of the platform and to become center for development of new diagnostics and drug discovery. We are building up infrastructure for screening and hit to lead conversion, including our own ~150,000 compound library, which we will screen for medicinally relevant targets, taking just one week per target. The most promising compounds will be optimized for potency, selectivity, physical properties, pharmacology profile and in vitro and in vivo efficacy, where DIANA-based high-throughput ADME pharmacology tests can also be applied. In our talk, we will briefly summarize the assay protocol and its performance on model targets, as well as recent developments at DIANA Biotechnologies. We will discuss in more detail examples of current internal projects, mainly of the development of selectivity panels (example of inhibitors of human carbonic anhydrases) and of the first drug discovery project directed on influenza RNA polymerase and its different subunits.

    Single and multi-frequency saturation methods for molecular and microstructural contrast in human MRI”

    Date:
    20
    Thursday
    June
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Elena Vinogradov
    Organizer: Department of Materials and Interfaces
    Abstract: Magnetic Resonance Imaging (MRI) provides excellent quality images of soft tissu ...Magnetic Resonance Imaging (MRI) provides excellent quality images of soft tissues and is an established modality for diagnosis, prognosis and monitoring of various diseases. Majority of MRI scans in clinical practice today report on anatomy, morphology and sometimes physiology. The new area of active studies is aimed at developing MRI contrast methods for the detection of the events at the microstructural and molecular level employing endogenous properties. Here, we will discuss methods that employ single- and multi-frequency saturation to detect events on microstructural and molecular level. First, we will describe principles and translational aspects of Chemical Exchange Saturation Transfer1(CEST). CEST employs selective saturation of the exchanging protons and subsequent detection of the water signal decrease to create images that are weighted by the presence of a metabolite or pH2. We will describe aspects of translating CEST to reliable clinical applications and discuss its potential uses in human oncology, specifically breast cancer. Second, we will describe a method called inhomogeneous Magnetization Transfer3 (ihMT), which employs dual-frequency saturation to create contrast originating from the residual dipolar couplings and thus specific to microstructure. We will focus on the application of ihMT to the detection of myelin in brain and spinal cord. Finally, we will discuss a novel exchange-sensitive method based on the balanced steady-state free precession (bSSFP) sequence as an alternative way for chemical exchange detection (bSSFPX4). Using an effective field description, similarities between bSSFP and CW application can be explored and utilized for in-vivo MRI contrast. [1] K. Ward, et.al., JMR,143,79-87 (2000). [2] J. Zhou, et.al., Nature Medicine, 9,1085-1090 (2003). [3] G. Varma, et.al., MRM, 73, 614-622 (2015). [4] S. Zhang, et.al., JMR, 275, 55-67 (2017).

    Highly resolved expression programs revealed by single-cell RNA-seq of a large virus infecting a bloom-forming alga

    Date:
    18
    Tuesday
    June
    2019
    Lecture / Seminar
    Time: 11:30-12:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Chuan Ku
    Organizer: Department of Plant and Environmental Sciences
    Details: Host: Prof. Assaf Vardi

    Learning how to make new β cells: molecular mechanisms underlying reprogramming of exocrine pancreas cells into insulin-producing β cells

    Date:
    18
    Tuesday
    June
    2019
    Lecture / Seminar
    Time: 10:30-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Ofer Elhanani
    Organizer: Department of Biomolecular Sciences
    Abstract: Diabetes is a life-threatening disease caused by insufficient circulating insuli ...Diabetes is a life-threatening disease caused by insufficient circulating insulin, a key metabolic hormone produced by pancreatic β cells. A promising approach to diabetes treatment is cell replacement therapy, yet this is currently limited by shortage of donor β cells. To address this, direct reprogramming of somatic non-β cells has been suggested as a potential source of β cells. The goal of this research is to clarify the molecular mechanisms involved in the process of reprogramming to β cells. We developed and characterized an in vitro system for reprogramming of primary mouse pancreatic acinar cells to β-like cells. Reprogrammed cells exhibit many similarities to native β-cells. Furthermore, this system allowed the identification of the transcriptional repressor REST (RE-1 silencing transcription factor) as a novel regulator of reprogramming which acts by modifying the chromatin around endocrine gene enhancers, thereby altering accessibility and function of endocrine transcription factors. Improved understanding of the mechanisms underlying reprogramming are essential to permit its application in the future for regenerative and cell therapy-based treatment of diabetes.

    RNASEQ Predicts Major Breast Cancer Subtype and Potential to Respond to Cancer Immunotherapy.

    Date:
    18
    Tuesday
    June
    2019
    Lecture / Seminar
    Time: 10:00-10:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Daniel Harari
    Organizer: Department of Biomolecular Sciences
    Abstract: Breast cancer (BC) divides into three major subtypes. 1) Estrogen/Progesterone ...Breast cancer (BC) divides into three major subtypes. 1) Estrogen/Progesterone Receptor positive (ER+ve), 2) ErbB2/Her2 genome amplified (Her2+), and for cancers exhibiting none of these markers, triple negative breast cancer (TNBC). These classifications defined by histo-pathologists have important ramifications as they indicate alternative therapy options best suited to treat a given patient. We have used high throughput transcriptomic data from > 1000 breast cancer biopsies derived from The Cancer Genome Atlas (TCGA) and demonstrate that RNASEQ can with high fidelity subcategorize BC into one of these three major subgroups. Surprisingly, we found that three levels of ErbB2 expression ErbBLOW, ErbB2MED and ErbB2HIGH closely correlate with TNBC, ER+ and HER+ tumor subtypes respectively, a finding not paralleled by genome copy-number alone. Pathway analyses of differentially expressed genes demonstrated that TNBCs are particularly enriched for “Lymphocyte Activation” correlating with “chemotaxis”, “NK-cell activation” and “IFN-gamma signaling”. These immune-related gene signatures may provide an additional layer of clinically-relevant patient information as others have reported that T-cell infiltration into tumors indicate potential good response to cancer immunotherapy (e.g. Anti-PD1, Anti-CTLA4 drugs). We can use these transcriptomic immune signatures to determine their level of expression in individual patients, thus providing context for predicting response to immunotherapy in personalized medicinal manner.

    Life Science Colloquium

    Date:
    17
    Monday
    June
    2019
    Colloquium
    Time: 14:00-15:00
    Title: Phase separation in biochemistry and disease
    Location: Dolfi and Lola Ebner Auditorium
    Lecturer: Prof. Anthony Hyman
    Organizer: Life Sciences

    Brain control and readout at biologically relevant resolutions

    Date:
    17
    Monday
    June
    2019
    Lecture / Seminar
    Time: 11:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Or Shemesh
    Organizer: Department of Neurobiology
    Details: Host: Prof. Rony Paz rony.paz@weizmann.ac.il tel: 6236 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: Understanding the neural basis of behavior requires studying the activity of neu ...Understanding the neural basis of behavior requires studying the activity of neural networks. Within a neural network, single neurons can have different firing properties, different neural codes and different synaptic counterparts. Therefore, it will be useful to readout from the brain and control it at a single-cell resolution. However, until recently, single cell readout and control in the brain were not feasible. The first scientific problem we addressed, is this regard, was the low spatial resolution of light based neural activation. Opsins are genetically encoded light switches for neurons that cause neural firing, or inhibition, when illuminated (and are therefore called “opto-genetic” molecules). However, optogenetic experiments are biased by ‘crosstalk’: the accidental stimulation of dozens of cells other than the cell of interest during neuron photostimulation. This is caused by expression of optogenetic molecules through the entirety of the cells, from the round cell body (“soma”) to the elongated neural processes. Our solution was molecular-focusing: by limiting the powerful opsin CoChR to the cell body of the neuron, we discovered that we could excite the cell body of interest alone. This molecule, termed “somatic-CoChR” was stimulated with state of the art holographic stimulation to enable millisecond temporal control which can emulate actual brain activity. Thus, we achieved for the first time single cell optogenteic stimulation at sub millisecond temporal precision. A second challenge was imaging the activity of multiple cells at a single cell resolution. The most popular neural activity indicator is the genetically encoded calcium sensor GCaMP, due to its optical brightness and high sensitivity. However, the fluorescent signal originating from a cell body is contaminated with multiple other fluorescent signals that originate from neurites of neighboring cells. This leads to a variety of artifacts including non-physiological correlation between cells and an impaired ability to distinguish between signals coming from different cells. To solve this, we made a cell body-targeted GCaMP. We screened over 30 different targeting motifs for somatic localization of GCaMP, and termed the best one, in terms of somatic localization, “SomaGCaMP”. This molecule was tested in live mice and zebrafish and can report the activity of thousands of neurons at a single cell resolution. A third challenge was voltage imaging in the brain, since genetically encoded indicators still suffered from either low sensitivity, or from low brightness. To record voltage, we used nitrogen vacancy nanodiamonds, known to be both very bright and sensitive to electric fields. Our aim was to bring the nanodiamonds to the membrane so the large electric field created by the action potential could impinge upon them and change their fluorescence. By making the nanodiamonds hydrophobic through surface chemistry modification, and inserting them into micelles, we labeled neural membranes with monodisperse diamonds for hours. We are now in the process of assessing the sensitivity of the nanodiamonds to the membrane voltage. Altogether, thinking backwards from fundamental limitations in neuroscience is instrumental in deriving strategies to fix these limitations and study the brain. In the future, we will use similar approaches to study and heal brain disease, at single-cell and subcellular resolutions.

    SERGIO LOMBROSO AWARD IN CANCER RESEARCH CEREMONY AND SYMPOSIUM

    Date:
    17
    Monday
    June
    2019
    Lecture / Seminar
    Time: 09:00
    Location: David Lopatie Conference Centre
    Organizer: Life Sciences

    SERGIO LOMBROSO AWARD IN CANCER RESEARCH CEREMONY AND SYMPOSIUM

    Date:
    17
    Monday
    June
    2019
    Lecture / Seminar
    Time: 09:00-12:00
    Location: David Lopatie Conference Centre
    Organizer: Department of Molecular Cell Biology
    Details: 09:00 Gathering 09:30 Sergio Lombroso Award in Cancer Research ceremony In the presence of the Lombroso family 2018 Recipient - Prof. Benny Geiger Weizmann Institute of Science, Rehovot 2019 Recipient - Prof. Karen Vousden Francis Crick Institute, London 09:45 Prof. Karen Vousden Francis Crick Institute, London “Playing with fire: the complex roles of p53 in the control of tumour development” 10:30 Coffee Break 10:50 Prof. Benny Geiger Weizmann Institute of Science, Rehovot “The mechanisms underlying invasive migration of metastatic cancer cells” 11:20 Dr. Ayelet Erez Weizmann Institute of Science, Rehovot "Modulating amino acid metabolism in cancer for immunotherapy" 11:50 Dr. Ravid Straussman Weizmann Institute of Science, Rehovot “The tumor microbiome”

    A Comprehensive Mechanistic Biological Theory of Brain Function

    Date:
    16
    Sunday
    June
    2019
    Lecture / Seminar
    Time: 11:00
    Location: Camelia Botnar Building
    Lecturer: Prof. Ari Rappoport
    Organizer: Department of Neurobiology
    Details: Short Bio: Ari Rappoport is a Full Professor of Computer Science at the Hebrew University. His CS area of expertise is Natural Language Processing, where he focuses on semantic representations. He started developing his brain theory in 2010, completing it at the end of 2017. Host: Prof. Ehud Ahissar ehud.ahissar@weizmann.ac.il tel: 4574 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: The brain is the target of intense scientific study, yet currently there is no t ...The brain is the target of intense scientific study, yet currently there is no theory of how it works at the system level. In this talk I will present the first such theory. The theory is biological and concrete, showing how motor and cognitive capacities arise from relatively understood biological entities. The main idea is that brain function is managed by a response (R) process whose structure is very similar to the process guiding the immune system. The brain has two instances of the R process, managing execution and need satisfaction. The stages of the execution process are implemented by different neural circuits, explaining the roles of cortical layers, the different types of inhibitory interneurons, hippocampal fields and basal ganglia paths. The stages of the need process are supported by different molecular agents, explaining the roles of dopamine, serotonin, ACh, opioids and oxytocin. The same execution process gives rise to hierarchical motor sequences, language, and imagery, while the need process explains feelings/emotions and consciousness in a mechanistic manner. The theory includes some aspects that are dramatically different from accepted accounts, e.g., the roles of basal ganglia paths, serotonin and opioids. The scope of the addressed phenomena is large, but they are all explained quite simply by the R process.

    Cancer Prevention Research: Looking to the Future

    Date:
    13
    Thursday
    June
    2019
    Conference
    Time: 08:30-16:30
    Location: David Lopatie Conference Centre
    Organizer: The M.D. Moross Institute for Cancer Research

    Halide Perovskites as a polymorphous network with a distribution of local motifs

    Date:
    12
    Wednesday
    June
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Alex Zunger
    Organizer: Department of Materials and Interfaces
    Abstract: While octahedral tilting or B atom displacements as a single repeated structural ...While octahedral tilting or B atom displacements as a single repeated structural motif are well known in perovskites, we find that removing the standard restriction to such a minimal unit cell size leads in some perovskites to the formation of a ‘polymorphous network’, manifesting a distribution of different tilt angles and different B-atom displacement in different octahedra. The distribution of local motifs emerges already from the (density functional) minimization of the static, T=0 internal energy of a large supercell, constrained to have the global cubic lattice vectors. This a-thermal distribution represents a correlated set of displacements and is very different from the time-dependent uncorrelated entropic thermal disorder calculated by Molecular Dynamics, or from the single sharp monomorphous values of these deformation parameters . This suggests that the widely discussed single formula unit cubic Pm-3m structure of halide perovskites does not really exist, except as a macroscopically averaged fictitious structural model. Because X-ray diffraction has a rather long coherence length, such polymorphous systems were often fit in structure refinement models by a macroscopically averaged (“fictitious monomorphous”) cubic Pm-3m unit cells. Significantly, compared to the monomorphous assumption, the cubic polymorphous network affects Pair Distribution Function (PDF), total energies, up to 300% larger band gaps, leads to the reversal of the predicted sign of the mixing enthalpies of the solid solutions from negative (ordering-like; not seen experimentally) to positive (experimentally observed phase-separating).Also, the polymorphous networks have a much larger (by ~50%) calculated dielectric constant, yet a relatively narrow energy range of vacancy transition levels and sharp absorption onset.defect physics. The polymorphous approximant could thus serve as a useful practical structure to use with standard band structure approaches to predict properties, replacing the fictitious monomorphous structures .

    Dysregulation of alternative splicing in cancer and its modulation as therapy

    Date:
    06
    Thursday
    June
    2019
    Lecture / Seminar
    Time: 13:00-14:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Rotem Karni
    Organizer: Department of Biological Regulation

    Non-Hydrolytic Sol-Gel Synthesis of Micro/Mesoporous Silicate and Phosphate Materials

    Date:
    05
    Wednesday
    June
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Jiri Pinkas
    Organizer: Department of Materials and Interfaces
    Abstract: Synthetic methods based on sol-gel chemistry are attractive solution-based route ...Synthetic methods based on sol-gel chemistry are attractive solution-based routes to many simple and complex materials. The non-hydrolytic procedures are viable alternatives to classical aqueous techniques and these condensation reactions are inherently suitable for fabrication of mixed-metal and multimetallic oxidic and hybrid inorganic-organic systems. We developed novel non-hydrolytic sol-gel routes to several classes of porous xerogels, such as silicophosphates and -phosphonates, aluminophosphates, Al, Ti, Zr, and Sn silicates, hybrid aromatic organosilicates, and organosilicophosphates. The polycondensation reactions are based on elimination of small molecules, such as trimethylsilyl ester of acetic acid, dialkylacetamides, silylamines, ethers or alcohols. These elimination reactions provide microporous xerogels with high surface areas. Control of porosity and pore size is achieved by several methods, such as choice of suitable precursors, application of bridging groups, or addition of Pluronic templates. Residual organic groups on the surface allow for chemical modification and anchoring of various groups. Calcination in air provides xerogels that are stable at temperatures up to 500 C and show superior catalytic activity and selectivity in various catalytic reactions. The prepared xerogels were characterized by solid-state 13C, 27Al, 29Si, 31P NMR, IR, surface area analysis, DRUV-vis, TGA and XRD

    Phosphorus-Element Bond-Forming Reactions

    Date:
    04
    Tuesday
    June
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Prof. Christopher C. Cummins
    Organizer: Department of Organic Chemistry
    Abstract: Reactive Intermediates & Group Transfer Reactions. We design and synthesize mol ...Reactive Intermediates & Group Transfer Reactions. We design and synthesize molecular precursors that can be activated by a stimulus to release a small molecule of interest. The molecular precursors themselves are isolated as crystalline solids; they are typically soluble in common organic solvents and can be weighed out and used as needed. For example, the molecule P2A2 (A = anthracene or C14H10) is a molecular precursor to the diatomic molecule P2. Compounds having the formula RPA serve to transfer the phosphinidene (PR) group either as a freely diffusing species (R = NR’2, singlet phosphinidene) or else by inner sphere mechanisms (R = alkyl, triplet phosphinidene). Using the RPA reagents we are developing reactions analogous to cyclopropanation and aziridination for delivery of the PR group to olefins with the formation of three-membered P-containing rings, phosphiranes. Metaphosphates and Phosphorylating Methodology. Crystalline metaphosphate salts with lipophilic counter cations are useful starting materials applicable in polar organic media. “Metaphosphate” refers to the inorganic ion PO3(-) which, unlike its chemical cousin, nitrate, exists not as a monomeric species but rather as oligomeric rings: [(PO3)n]n-. These cyclic phosphates can be converted into electrophilic phosphorylating agents (a) by treatment with peptide coupling reagents, or (b) by conversion into their crystalline acid forms and subsequent dehydration. Such activated cyclic phosphates can be used directly for oligophosphorylation of C, N, and O nucleophiles. Phosphorylation of the Wittig reagent leads to a new phosphorus ylide with a cyclic phosphate as the C-substituent and a non-hydrolyzable P-C bond, allowing for conjugation of oligophosphate groups to a biomolecule of interest by aldehyde olefination. Sustainable Phosphorus Chemistry. The industrial “thermal process” by which the raw material phosphate rock is upgraded to white phosphorus is energy intensive and generates CO2. We seek alternative chemical routes to value-added P-chemicals from phosphate starting materials obtained either by the agricultural “wet process” or by phosphorus recovery and recycling from waste streams. Trichlorosilane is a high production volume chemical for its use in the manufacture of silicon for solar panels. We show that trichlorosilane is a reductant for phosphate raw materials leading to the bis(trichlorosilyl) phosphide anion [P(SiCl3)2]- as a versatile intermediate en route to compounds containing P-C bonds.

    The importance of tight regulation of global mRNA translation to brain function and cellular division (two stories)

    Date:
    04
    Tuesday
    June
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Orna Elroy-Stern
    Organizer: Department of Biomolecular Sciences
    Abstract: The first story deals with the dramatic influence of mutations in eIF2B genes on ...The first story deals with the dramatic influence of mutations in eIF2B genes on the brain. eIF2B is a master regulator of protein synthesis under normal and stress conditions. We developed a mouse model harboring a mutation leading to only 20% decrease in eIF2B enzymatic activity. The effect on mitochondria function and hyper-sensitivity of CNS glial cells will be discussed. Our study revealed the identification of a potential drug for eIF2B-leukodystrophy (VWM disease). The second story deals with the surprising involvement of hnRNP C as a positive translation regulator during mitosis. hnRNP C enhances the translation of a sub-class of mRNAs encoding components of the translation machinery itself. Surprisingly, at metaphase & anaphase hnRNP C collocalizes with active ribosomes noticeably at the cell cortex.

    FAK Family Kinases: The Yin and Yang of Cancer Metastasis

    Date:
    30
    Thursday
    May
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Hava Gil
    Organizer: Department of Biological Regulation

    Chemical and Biological Physics Guest Seminar

    Date:
    30
    Thursday
    May
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Title: Mechanics of cells and tissues
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Alexandre Kabla
    Organizer: Department of Chemical and Biological Physics
    Abstract: Cell migration and cell mechanics play a crucial role in a number of key biologi ...Cell migration and cell mechanics play a crucial role in a number of key biological processes, such as embryo development or cancer metastasis. Understanding the way cells control their own material properties and mechanically interact with their environment is key. At a more fundamental level, there is need better measure, describe and monitor cell and tissue mechanics before we can formulate testable hypotheses. In this talk, I will report experimental studies on the mechanical response of two different multicellular structures: epithelial monolayers and early embryonic tissues. In both cases, the material exhibits a strong time-dependent response over a broad distribution of time-scales. The combination of mechanical characterisation with biological perturbations offers new insight into the mechanisms exploited by cells and tissue to control their mechanical properties. This insight is however limited by the lack of consistency in experimental protocols and modelling strategies used in the field. We recently developed a systematic approach to capture material properties from mechanical behaviours and made progress assessing the model’s generality over a broad range of biological systems

    Synthetic interferon receptors transmit biological signals using artificial ligands

    Date:
    28
    Tuesday
    May
    2019
    Lecture / Seminar
    Time: 10:30-10:45
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Eyal Zoler
    Organizer: Department of Biomolecular Sciences
    Abstract: Interferons (IFNs) were the first cytokines discovered over half a century ago a ...Interferons (IFNs) were the first cytokines discovered over half a century ago as agents that interfere with viral infection. IFNs have been established as pleiotropic, multifunctional proteins in the early immune response. They exhibit antiviral and antiproliferative effects, in addition to various immunomodulatory activities. Human type I IFN family consists of 16 members, all acting through the same cell surface receptors, IFNAR1 and IFNAR2. Here, we show that synthetic interferon receptors can activate the Jak/Stat pathway using non-physiological ligands. High affinity GFP and mCherry nanobodies were fused to transmembrane and intracellular domains of the receptors in attempt to perform in-vivo and in-vitro biophysical assays. This will help in better understanding the structure - function relationship of the receptors and their associated ligands.

    Revealing the dynamic stability of fusion pores in giant vesicles through live, super-resolution microscopy

    Date:
    28
    Tuesday
    May
    2019
    Lecture / Seminar
    Time: 10:00-10:15
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Tom Biton
    Organizer: Department of Biomolecular Sciences
    Abstract: Exocytosis occurs in all living cells and is essential for many cellular process ...Exocytosis occurs in all living cells and is essential for many cellular processes including metabolism, signaling, and trafficking. During exocytosis, cargo loaded vesicles dock and fuse with the plasma membrane to release their content. To accommodate different cargos and cellular needs exocytosis must occur across scales; From synaptic vesicles that are only ~50nm in diameter, and neuroendocrine vesicles that are in the ~500nm range to giant secretory vesicles filled with viscous cargo, such as in the acinar cells in the exocrine pancreas, that reach up to a few µm in diameter. Yet, how fusion and content release are adapted to remain function across these scales is not well understood. It is well established that during exocytosis of small vesicles, vesicle fusion can proceed through one of two pathways: The first is complete incorporation, when the vesicular membrane fuses to the target membrane and the fusion pore expand irreversibly, incorporating the vesicular membrane into the target membrane. The second is “kiss-and-run”, when the fusion pore flickers, opening briefly and collapsing rapidly into two separate membranes. I am interested in understanding how exocytosis occurs in giant vesicles witch challenge efficient secretion and membrane homeostasis due to their massive size and viscous content. I am using the salivary gland of D. Melanogaster, as a model system for giant vesicles secretion. The vesicles in the gland measure between 5-8 µm, fuse and secrete viscous content into a preformed lumen. To visualize the secretion process, I adapted a method for super-resolution microscopy to live-gland imaging. I observed that fusion pores of giant vesicles expand to a stable opening of up to 3µm and slowly constricts down to hundreds of nm or less during secretion. Because constricting a membrane pore from “infinity” in molecular terms, back to a very narrow ‘stalk’ demands an investment of energy, I hypothesized that this is mediated by a specialized protein machinery. I am currently screening for the components of the machinery using the enormous power of Drosophila genetics by taking a candidate gene approach. My preliminary results identify the BAR domain containing protein, MIM (missing in metastasis) as a key regulator of pore dynamics, leading to new and exciting insights into the molecular mechanism of cellular secretion and membrane homeostasis in live tissues.

    Beta cell workload and type 2 diabetes risk

    Date:
    26
    Sunday
    May
    2019
    Lecture / Seminar
    Time: 15:00-16:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Benjamin Glaser
    Organizer: Life Sciences

    Departmental Seminar

    Date:
    26
    Sunday
    May
    2019
    Lecture / Seminar
    Time: 13:00-14:00
    Title: Developing a highly sensitive CRISPR based platform for virus and host functional genomics
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Yaara Finkel
    Organizer: Department of Molecular Genetics

    Can Biosensors Cure Mental Illness

    Date:
    21
    Tuesday
    May
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Jacob Pearson keller
    Organizer: Department of Biomolecular Sciences
    Abstract: One in five people in the US currently experiences a mental illness, and yet, de ...One in five people in the US currently experiences a mental illness, and yet, despite significant clinical and pharmacological efforts, little progress has been made against this "silent plague." Recently, however, a number of unconventional psychoactive drugs--notably ketamine, MDMA (ecstasy), psilocybin, and others--have shown dramatic, unprecedented clinical efficacy in treating depression, post-traumatic stress disorder (PTSD), and anxiety disorders, among others. Perhaps because of a history of sociopolitical and legal barriers to the study of these compounds, much still remains to be elucidated about their underlying neural mechanisms. It would appear that the time has come not only to develop a clearer picture of the mechanisms of their psychoactive activity per se, but also to decipher their pharmacological connections to normal and pathological cognitive processes. This can now be done at several scales (from molecular-level to the whole-brain) by using genetically encoded fluorescent biosensors, which non-invasively report drug-induced functional perturbations. In this talk, recent biosensor highlights will be described, promising data on psychoactives presented, and specific future directions sketched. By leveraging biosensors and psychoactive drugs, a mechanistic foundation can built from which real cures to mental illness can be found.

    Weizmann-India Exchange: Chemical Biology

    Date:
    14
    Tuesday
    May
    2019
    -
    16
    Thursday
    May
    2019
    Conference
    Time: 08:00
    Location: Wolfson Building for Biological Research
    Organizer: Feinberg Graduate School

    Stress and inflammation in tumor progression and metastasis

    Date:
    13
    Monday
    May
    2019
    -
    15
    Wednesday
    May
    2019
    Conference
    Time: 12:00 - 17:00
    Location: David Lopatie Conference Centre

    Deconstructing and reconstructing the ovarian cancer microenvironment

    Date:
    13
    Monday
    May
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Title: Cancer Research Club
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Frances Balkwill
    Organizer: Department of Biological Regulation

    Structure-Activity Relationship by Kinetics for Drug Discovery in Protein Misfolding Diseases

    Date:
    05
    Sunday
    May
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Michele Vendruscolo
    Organizer: Department of Materials and Interfaces

    UVB-Induced Tumor Heterogeneity Directs Immune Response in Melanoma

    Date:
    02
    Thursday
    May
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Title: CANCER RESEARCH CLUB
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Yardena Samuels
    Organizer: Department of Biological Regulation

    Modulation of T-cell activity by the human T-cell leukemia virus fusion peptide

    Date:
    30
    Tuesday
    April
    2019
    Lecture / Seminar
    Time: 10:00-10:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Eita Rotem
    Organizer: Department of Biomolecular Sciences
    Abstract: In order to infect and persist in their hosts, viruses utilize multiple strategi ...In order to infect and persist in their hosts, viruses utilize multiple strategies to evade the immune system. HIV utilizes membrane interacting regions of its envelope protein, primarily used to fuse with its target cells, to inhibit T-cell activation. Yet, it is unknown whether this ability is shared with other viruses. We examined the T-cell inhibitory activity of HTLV-1, focusing on a functionally conserved region of HTLV’s and HIV’s fusion proteins, the fusion peptide (FP). Here, we reveal that HTLV’s FP modulates T-cell activity in-vitro and in-vivo. This modulation is characterized by downregulation of the Th1-response, leading to an elevated Th2-response observed by transition in mRNA, cytokines and regulatory proteins. Our findings suggest that FP mediated immune evasion might be a trait shared between different viruses.

    Cellular Signaling in Health and Disease

    Date:
    29
    Monday
    April
    2019
    -
    30
    Tuesday
    April
    2019
    Conference
    Time: 08:00
    Location: Max and Lillian Candiotty Building
    Organizer: Department of Biological Regulation

    CRASH COURSE ON GENOMICS and BIOINFORMATICS OF CANCER

    Date:
    18
    Thursday
    April
    2019
    Lecture / Seminar
    Time: 11:45-14:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Eytan Ruppin, Prof. Itay Tirosh
    Organizer: Department of Biomolecular Sciences

    Bipolar Disorder: Predicting Outcomes and Identifying Mechanisms

    Date:
    17
    Wednesday
    April
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Dr. Melvin G. McInnis
    Organizer: Department of Molecular Cell Biology

    Brain cell type analysis and why it matters for disease

    Date:
    16
    Tuesday
    April
    2019
    Lecture / Seminar
    Time: 14:00
    Location: Camelia Botnar Building
    Lecturer: Prof. Jens Hjerling-Leffler
    Organizer: Department of Neurobiology
    Details: Host: Dr.Ivo Spiegel ivo.spiegel@weizmann.ac.il tel: 4415 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: Cellular complexity in the brain has been a central area of study since the birt ...Cellular complexity in the brain has been a central area of study since the birth of cellular neuroscience over a hundred years ago. Several different classification systems have been put forward based on emerging techniques. It is still largely unclear if and how the classification system produced using recent single-cell transcriptomics corresponds to previous classification systems. The interneurons of the hippocampus has been extensively characterised on physiological and morphological basis and we used this classification as a basis to compare single-cell RNA sequencing data from the CA1 hippocampus. We show, using the in situ sequencing technique “pciSeq” that the predictions made from scRNAseq data corresponds existing classification. Furthermore, we leverage the rich data from scRNAseq and combined it with GWAS data from patients to begin to elucidate the cellular origin of genetic heritability of brain disorders. Although many of these disorders are genetically complex it seems that specific and sometimes non-overlapping cell types underlie the ethology of these disorders. For instance we show a largely ignored role of oligodendrocytes in Parkinson’s disease which can be confirmed in patient material. This proves the feasibility to link modern transcriptomics with genetics to leverage the recent advances in understanding of genetic structure of brain disorders to yield actionable targets.

    The mechanics of malaria parasite invasion of the red cell (and beyond): seeking a balanced view of parasite-host contributions to entry

    Date:
    16
    Tuesday
    April
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Jacob Baum
    Organizer: Department of Biomolecular Sciences
    Abstract: Entry of the malaria parasite merozoite, the micron sized cell responsible for b ...Entry of the malaria parasite merozoite, the micron sized cell responsible for blood-stage malaria infection, into the human red blood cell defines establishment of malaria disease. The process is rapid yet contains a great depth of cell biology, one eukaryotic cell actively penetrating the other. Entry has long been seen as a very parasite-centric process with the merozoite literally driving its way into a passive erythrocyte. This is in marked contrast to other pathogens that utilise host-cell phagocytosis to gain entry to human cells. Has this inbalanced view been over-stated in the case of the merozoite? Recent data from several groups suggests that erythrocyte biophysics (including membrane biophysical properties) also contributes to the process of merozoite entry. Here, I will present our latest insights into the role of both parasite and host cell factors and how they might be contributing to lowering the energy barrier required to get the merozoite inside the human red blood cell. With a particular focus on cell imaging, I will present our vision of invasion being a balanced equation with parasite motor force and host membrane deformability both contributing to allow the blood-stage malaria parasite (and may be beyond the blood stages) get in.

    Sustaining Life with Genes and Proteins Designed De Novo

    Date:
    15
    Monday
    April
    2019
    Lecture / Seminar
    Time: 16:00-17:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Michael Hecht
    Organizer: Department of Biomolecular Sciences
    Abstract: A key goal of synthetic biology is to design novel proteins that fold and functi ...A key goal of synthetic biology is to design novel proteins that fold and function in vivo. A particularly challenging objective would be to produce non-natural proteins that don’t merely generate interesting phenotypes, but which actually provide essential functions necessary to sustain life. Successful design of life-sustaining proteins would be a significant step toward constructing entirely artificial “proteomes.” In initia! l work toward this goal providing activities necessary to sustain the growth of living cells. In some cases, the novel proteins rewire gene regulation. In others, the novel protein sustains cell growth by functioning as in vivo, we have designed large libraries of novel proteins encoded by millions of synthetic genes. Many of these proteins fold into stable 3-dimensional structures; and many bind metals, metabolites, and cofactors. Several of the novel proteins function bona fide enzyme that catalyzes an essential biochemical reaction. These results suggest (i) The molecular toolkit of life need not be limited to sequences that already exist in nature; (ii) Synthetic genomes and artificial proteomes can be built from non-natural sequences; (iii) Construction of alternative lifeforms may soon be possible.

    Life Science Colloquium

    Date:
    15
    Monday
    April
    2019
    Colloquium
    Time: 11:00-12:00
    Title: Mechanical LINCages to the nucleus in cell polarity, migration and disease
    Location: Wolfson Building for Biological Research
    Lecturer: Prof. Gregg Gundersen
    Organizer: Life Sciences

    Mechanisms of longevity and cancer-resistance: lessons from long-lived animals

    Date:
    14
    Sunday
    April
    2019
    Lecture / Seminar
    Time: 11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Vera Gorbunova & Prof. Andrei Seluanov
    Organizer: Life Sciences
    Details: Host: Prof. Avraham Levy

    Symposium Honoring the 90th Birthday of Prof. Ernest Winocour- Viruses, Gene Therapy

    Date:
    14
    Sunday
    April
    2019
    -
    15
    Monday
    April
    2019
    Conference
    Time: 08:00
    Location: David Lopatie Conference Centre

    Applying cancer unique metabolism for patients’ diagnosis and therapy

    Date:
    11
    Thursday
    April
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Ayelet Erez
    Organizer: Department of Biological Regulation

    Epigenetic pathways as targets in human disease

    Date:
    11
    Thursday
    April
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Shelley Berger
    Organizer: Department of Biological Regulation

    IMM Guest seminar- Dr. Tomer Hertz will lecture on "A journey into influenza antigenic space using systems serology".

    Date:
    08
    Monday
    April
    2019
    Lecture / Seminar
    Time: 13:00
    Location: Wolfson Building for Biological Research
    Lecturer: Dr. Tomer Hertz
    Organizer: Department of Immunology
    Abstract: Vaccination is an effective tool for preventing influenza infection. A variety o ...Vaccination is an effective tool for preventing influenza infection. A variety of factors have been shown to impact the observed heterogeneity and inter-individual variations in immune responses following vaccination including age, gender, ethnicity and immunological history (the individual's memory antibody repertoire to previously encountered pathogens and vaccines). Throughout life individuals are infected by and vaccinated with multiple influenza strains and develop a broad and diverse influenza Ab repertoire. We have been developing a novel low-volume antigen microarray assay for profiling influenza immunological history, and used it to assess the effects of immune history on vaccine-induced immunogenicity and protection, using samples from an influenza vaccine efficacy trial, as well as to characterize the maternal fetal transfer of influenza specific antibodies.

    NK cells in Cancer: The next Breakthrough?

    Date:
    07
    Sunday
    April
    2019
    Conference
    Time: 08:00
    Location: Max and Lillian Candiotty Building
    Organizer: Dwek Institute for Cancer Therapy Research

    Considering alternatives to targeted therapy of cancer

    Date:
    04
    Thursday
    April
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Yinon Ben-Neriah
    Organizer: Department of Biological Regulation

    IMM Guest seminar- Dr. Amiram Ariel will lecture on "New cellular and molecular effectors in macrophage-mediated resolution of inflammation."

    Date:
    01
    Monday
    April
    2019
    Lecture / Seminar
    Time: 13:00-14:00
    Location: Wolfson Building for Biological Research
    Lecturer: Dr. Amiram Ariel
    Organizer: Department of Immunology

    glucose-dependent insulinotrophic polypeptide (GIP )regulates whole body energy homeostasis via its effects on immune cells

    Date:
    31
    Sunday
    March
    2019
    Lecture / Seminar
    Time: 15:00-16:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Sigal Fishman
    Organizer: Life Sciences

    Mapping the Breakome of Cancer Cells: What Lessons have we Learned?

    Date:
    28
    Thursday
    March
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Rami Aqeilan
    Organizer: Department of Biological Regulation

    IMM Guest seminar- Prof.Yuval Shaked will lecture on "Therapy-induced a phenotype and functional switch in cells at the tumor microenvironment in response to therapy dictates tumor fate.""

    Date:
    25
    Monday
    March
    2019
    Lecture / Seminar
    Time: 13:00-14:00
    Location: Wolfson Building for Biological Research
    Lecturer: Prof. Yuval Shaked
    Organizer: Department of Immunology
    Details: Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular effects which, in turn, lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host effects is attributed to pro-inflammation, angiogenesis, tumor cell dissemination from the primary tumor and seeding at metastatic sites. Various bone marrow derived cells participate in this process, and many different factors are secreted from host cells in response to the therapy which then lead to tumor relapse and even resistance to therapy. The recent advances in cancer immunotherapy have significantly improved therapeutic outcomes in a subset of patients with advanced malignancies, still most patients do not respond to treatment and some even hyper progress. In my presentation, I will discuss several examples of how host cells undergo a functional and phenotype switch in response to therapy which contribute to tumor relapse and hyperprogression in response to therapy. I will also demonstrate how blocking the host pro-tumorigenic responses to therapy can minimize therapy resistance and improve therapy outcome.

    Exosomal transmission between macrophages and cancer cells: new insights to sroma-mediated drug resistance

    Date:
    21
    Thursday
    March
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Ziv Gil
    Organizer: Department of Biological Regulation

    “LAP and LANDO: Noncanonical functions of autophagy proteins in anti-cancer immunity and Alzheimer's Disease”

    Date:
    18
    Monday
    March
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Douglas R. Green
    Organizer: Department of Molecular Cell Biology

    Vav1: A Dr. Jekyll and Mr. Hyde protein--good for the hematopoietic system, bad for cancer

    Date:
    14
    Thursday
    March
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Special Guest Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Shulamit Katzav-Shapira
    Organizer: Department of Biological Regulation

    Spectral editing techniques for chemical exchange saturation transfer imaging

    Date:
    12
    Tuesday
    March
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Jiadi Xu
    Organizer: Department of Materials and Interfaces
    Abstract: Chemical exchange saturation transfer (CEST) imaging is a relatively new MRI tec ...Chemical exchange saturation transfer (CEST) imaging is a relatively new MRI technology allowing the detection of low concentration endogenous cellular proteins and metabolites indirectly through water. CEST MRI is still under development and one major impediment for more widespread application is limited specificity due to spectral overlap of CEST signal from other metabolites and proteins. In this presentation, I will demonstrate several novel CEST spectral editing techniques developed by our group to extract information from CEST images, such as one variable delay multi pulse (VDMP) CEST that acts an exchange rate filter to separate CEST effects from the confounding factors, one ultra-short echo (UTE)-CEST method that can monitor in vivo protein aggregation process and one polynomial and Lorentzian line-shape fitting (PLOF) CEST that can detect creatine and phosphocreatine in tissue with high specialty. Their applications on the stroke and Alzheimer’s disease models will be covered. At last, I will explore one artificial neural network approach to overcome the challenges of implementing the CEST technique on 3T clinical MRI scanners.

    "Supramolecular Assembly with Mechanical Action"

    Date:
    11
    Monday
    March
    2019
    Colloquium
    Time: 11:00-12:30
    Title: title tbd
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Myongsoo Lee
    Organizer: Faculty of Chemistry
    Abstract: In this symposium, I will introduce our recent results how to construct dynamic ...In this symposium, I will introduce our recent results how to construct dynamic self-assembled nanostructures exhibiting switchable functions, inspired by life systems. For example, synthetic tubular pores are able to undergo open-closed gating driven by an external signal, which function as an artificial enzyme. When self-assembled tubules embed DNA inside the hollow cavities, the DNA-coat assembly undergoes collective motion in helicity switching. In the case of toroid assembly, the static toroids are able to undergo spontaneous helical growth when they switch into out-of-equilibrium state. The helical growing drives actuation of spherical vesicles into tubular vesicles, reminiscent of microtubles. Moving from 1-D to 2-D structures, the internal pores are able to form chiral interior which selectively capture only one enantiomer in racemic solution with pumping action. I will discuss recently discovered these results with their complex functions.

    Photovoltaic Restoration of Sight in Retinal Degeneration

    Date:
    10
    Sunday
    March
    2019
    Lecture / Seminar
    Time: 12:30
    Location: Nella and Leon Benoziyo Building for Brain Research
    Lecturer: Prof. Daniel Palanker
    Organizer: Department of Neurobiology
    Details: Benoziyo Brain Research Building Room 113 Host: Dr. Michal Rivlin michal.rivlin@weizmann.ac.il tel: 2792 For assistance with accessibility issues, please contact liat.ms@weizmann.ac.il
    Abstract: Retinal degenerative diseases lead to blindness due to loss of the “image capt ...Retinal degenerative diseases lead to blindness due to loss of the “image capturing” photoreceptors, while neurons in the “image-processing” inner retinal layers are relatively well preserved. Information can be reintroduced into the visual system using electrical stimulation of the surviving inner retinal neurons. Some electronic retinal prosthetic systems have been already approved for clinical use, but they provide low resolution and involve very difficult implantation procedures. We developed a photovoltaic subretinal prosthesis which converts light into pulsed electric current, stimulating the nearby inner retinal neurons. Visual information is projected onto the retina from video goggles using pulsed nearinfrared (~880nm) light. This design avoids the use of bulky electronics and wiring, thereby greatly reducing the surgical complexity. Optical activation of the photovoltaic pixels allows scaling the implants to thousands of electrodes. In preclinical studies, we found that prosthetic vision with subretinal implants preserves many features of natural vision, including flicker fusion at high frequencies (>20 Hz), adaptation to static images, antagonistic center-surround organization and nonlinear summation of subunits in receptive fields, providing high spatial resolution. Results of the clinical trial with our implants (PRIMA, Pixium Vision) having 100µm pixels, as well as preclinical measurements with 75 and 55µm pixels, confirm that spatial resolution of prosthetic vision can reach the sampling density limit. For a broad acceptance of this technology by patients who lost central vision due to age-related macular degeneration, visual acuity should exceed 20/100, which requires pixels smaller than 25µm. I will describe the fundamental limitations in electro-neural interfaces and 3-dimensional configurations which should enable such a high spatial resolution. Ease of implantation of these wireless arrays, combined with high resolution opens the door to highly functional restoration of sight.

    The 2019 Justen Passwell Symposium Dynamics and Control of Infectious Disease in the Era of Antibiotic Resistance

    Date:
    06
    Wednesday
    March
    2019
    -
    07
    Thursday
    March
    2019
    Conference
    Time: 08:00
    Location: David Lopatie Conference Centre

    Structural Basis for Serum Amyloid A Function in Lipid Homeostasis and Immune Response: A Novel Function for an Ancient Protein

    Date:
    05
    Tuesday
    March
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Prof. Olga Gursky
    Organizer: Department of Structural Biology

    IMM Guest seminar- Prof. Benny Chain will lecture about "The T cell receptor repertoire in health and disease."

    Date:
    04
    Monday
    March
    2019
    Lecture / Seminar
    Time: 13:00-14:00
    Location: Wolfson Building for Biological Research
    Lecturer: Prof. Benny Chain
    Organizer: Department of Immunology

    EMERGING CONCEPTS IN BREAST CANCER

    Date:
    03
    Sunday
    March
    2019
    Lecture / Seminar
    Time: 11:00-14:00
    Title: Minerva and Dwek Institute for Cancer Therapy Research workshop
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Sima Lev, Prof. Stefan Wiemann, Prof. Carlos Caldas
    Organizer: Department of Biological Regulation

    Are you stressed? The molecular framework of the nutritional alarmones (p)ppGpp

    Date:
    26
    Tuesday
    February
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Gert Bange
    Organizer: Department of Biomolecular Sciences
    Abstract: The ability of bacteria to adapt their metabolism to nutrient limitation or envi ...The ability of bacteria to adapt their metabolism to nutrient limitation or environmental changes is essential for survival. The stringent response is a highly conserved mechanism that enables bacteria to respond to nutrient limitations. Central to stringent response is the synthesis of the nutritional alarmones pppGpp and ppGpp (collectively named: (p)ppGpp) that globally reprograms transcription and translation associated to variety of different cellular processes. In Bacillus subtilis and Staphylococcus aureus, three types of alarmone synthases (i.e., RelA, SAS1 and SAS2) have been identified that differ in length and domain composition. These differences might be attributed to their specific roles during stringent response. However, only little information on the molecular details is known. I will present our recent progress towards the structural/mechanistic understanding of the molecular framework of alarmone response.

    From brain organoids to animal chimera: Novel platforms for studying human brain development and disease

    Date:
    26
    Tuesday
    February
    2019
    Lecture / Seminar
    Time: 09:00-10:00
    Location: Wolfson Building for Biological Research
    Lecturer: Dr. Abed A. Mansour
    Organizer: Department of Neurobiology
    Abstract: Due to the immense complexity of the human brain, the study of its development, ...Due to the immense complexity of the human brain, the study of its development, function, and dysfunction during health and disease has proven to be challenging. The advent of patient-derived human induced pluripotent stem cells, and subsequently their self-organization into three-dimensional (3D) brain organoids, which mimics the complexity of the brain's architecture and function, offers an unprecedented opportunity to model human brain development and disease in new ways. However, there is still a pressing need to develop new technologies that recapitulate the long-term developmental trajectories and the complex in vivo cellular environment of the brain. To address this need, we have developed a human brain organoid-based approach to generate a chimeric human/animal brain system that facilitates long-term ana! tomical integration, differentiation, and vascularization in vivo. We also demonstrated the development of functional neuronal networks within the brain organoid and synaptic-cross interaction between the organoid axonal projections and the host brain. This approach set the stage for investigating human brain development and mental disorders in vivo, and run therapeutic studies under physiological conditions.

    Soft excitations in glassy systems: Universal statistics, localization and structure-dynamics relations

    Date:
    25
    Monday
    February
    2019
    Lecture / Seminar
    Time: 14:15
    Lecturer: Eran Bouchbinder
    Abstract: Glassy systems exhibit various universal anomalies compared to their crystalline ...Glassy systems exhibit various universal anomalies compared to their crystalline counterparts, manifested in their thermodynamic, transport and strongly dissipative dynamical properties. At the heart of understanding these phenomena resides the need to quantify glassy disorder and to identify excitations that are associated with it. In this talk, I will review our recent progress in addressing these basic problems. I will first establish the existence of soft nonphononic excitations in glasses, which has been debated for decades. These low-frequency glassy excitations feature a localization length in space and follow a universal gapless density of states, and they are associated with the generic existence of frustration-induced internal-stresses in glasses. I will then discuss two major implications of these localized excitations: (i) Their relation to soft spots inside glassy structures that can be identified once the spatial distribution of the heat capacity is considered. These allow us to develop predictive structure-dynamics relations in the context of irreversible (plastic) rearrangements under nonlinear driving forces. (ii) Their effect on energy transport, in particular I will show that they lead to deviations from Rayleigh scattering scaling in the attenuation of sound. Open questions will be briefly mentioned.

    Computational Design Principles of Cognition

    Date:
    24
    Sunday
    February
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Wolfson Building for Biological Research
    Lecturer: Dr. Yuval Hart
    Organizer: Department of Neurobiology
    Abstract: Driven by recent technological advancements, behavior and brain activity can now ...Driven by recent technological advancements, behavior and brain activity can now be measured at an unprecedented resolution and scale. This “big-data” revolution is akin to a similar revolution in biology. In biology, the wealth of data allowed systems-biologists to uncover the underlying design principles that are shared among biological systems. In my studies, I apply design principles from systems-biology to cognitive phenomena. In my talk I will demonstrate this approach in regard to creative search. Using a novel paradigm, I discovered that people’s search exhibits exploration and exploitation durations that were highly correlated along a line between quick-to-discover/quick-to-drop and slow-to-discover/slow-to-drop strategies. To explain this behavior, I focused on the property of scale invariance, which allows sensory systems to adapt to environmental signals spanning orders of magnitude. For example, bacteria search for nutrients, by responding to relative changes in nutrient concentration rather than absolute levels, via a sensory mechanism termed fold change detection (FCD). Scale invariance is prevalent in cognition, yet the specific mechanisms are mostly unknown. I found that an FCD model best describes creative search dynamics and further predicts robustness to variations in meaning perception, in agreement with behavioral data. These findings suggest FCD as a specific mechanism for scale invariant search, connecting sensory processes of cells and cognitive processes in human. I will end with a broader perspective and outline the benefits of the search for computational design principles of cognition.

    Shaping the Inflammatory Niche: Cancer-Associated Fibroblasts Facilitate Breast Cancer Metastasis

    Date:
    21
    Thursday
    February
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Neta Erez
    Organizer: Department of Biological Regulation

    IMM Guest seminar- Prof. Sergio A. Quezada will lecture on "Targeting regulatory T cells for therapeutic gain: from mechanisms to new therapies."

    Date:
    21
    Thursday
    February
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Camelia Botnar Building
    Lecturer: Prof. Sergio A. Quezada
    Organizer: Department of Immunology

    Translocation Mechanisms of Protein-Antibiotics

    Date:
    19
    Tuesday
    February
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Dr. Ruth Cohen Khait
    Organizer: Department of Structural Biology

    UV protection-timer and UV systemic effect

    Date:
    14
    Thursday
    February
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Carmit Levy
    Organizer: Department of Biological Regulation

    Dissecting pathways of neuroinflammation in Gaucher disease

    Date:
    12
    Tuesday
    February
    2019
    Lecture / Seminar
    Time: 10:30-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Ayelet Vardi
    Organizer: Department of Biomolecular Sciences
    Abstract: Gaucher disease (GD), a common lysosomal storage disorder (LSD), is caused by m ...Gaucher disease (GD), a common lysosomal storage disorder (LSD), is caused by mutations in the GBA1 gene. This gene encodes the lysosomal hydrolase glucocerebrosidase (GlcCerase), and in the disease, the lipid glucosylceramide (GlcCer) accumulates within the cell. Although neuronopathic Gaucher disease (nGD) was described over a hundred years ago, little is known about the mechanisms leading from GlcCer accumulation to neuronal cell death and inflammation. Recently, our laboratory identified induction of the type 1 interferon (IFN) response in nGD mice. The IFN response is the fundamental cellular defense mechanism against viral infection, however it can also be induced in the absence of infection. Ablation of the IFN receptor (IFNAR) did not have any effect on the viability of nGD mice. Therefore, we took availability of quadrat deficient mice where four adaptors of main pathogen recognition receptors (PRR) are blocked. Ablation of all the pathways leading to IFN production did not have effect on mice life span. Nevertheless, we utilized these results to conduct an RNA sequencing study with the goal of defining what are the inflammatory pathways lead to disease development and, eventually, to mice death.

    eIF1A promotes translation of cell cycle genes

    Date:
    12
    Tuesday
    February
    2019
    Lecture / Seminar
    Time: 10:00-10:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Urmila Sehrawat
    Organizer: Department of Biomolecular Sciences
    Abstract: Protein synthesis is linked to cell proliferation and its deregulation contribut ...Protein synthesis is linked to cell proliferation and its deregulation contributes to diseases such as cancer. eIF1A plays a key role in scanning and AUG selection and differentially affects translation of distinct mRNAs. Its unstructured N-terminal tail (NTT) is frequently mutated in several malignancies. Here, we show that eIF1A is essential for cell proliferation and cell-cycle progression. Ribosome-profiling of eIF1A knockdown cells revealed a substantial reduction in protein synthesis, with particular enrichment of cell-cycle mRNAs. The downregulated genes are predominantly characterized by lengthy 5’UTR. On the other hand, eIF1A depletion caused a broad stimulation of initiation in 5’UTRs at near-cognate AUG. Importantly, cancer-associated eIF1A-NTT mutants augment the positive effect of eIF1A on long 5’UTR while hardly affecting AUG selection. Our findings suggest that reduced binding of eIF1A NTT mutants to the ribosome retains its open state and facilitate scanning of long 5’UTR-containing cell cycle genes.

    IMM Guest seminar- Prof. Peter J. Murray will lecture on "Immune regulation by amino acid metabolism."

    Date:
    11
    Monday
    February
    2019
    Lecture / Seminar
    Time: 12:30
    Location: Wolfson Building for Biological Research
    Lecturer: Prof. Peter J. Murray
    Organizer: Department of Immunology

    Self-assemblies of designed B-sheet peptides as hydrogels, coatings and drug delivery nanoparticles

    Date:
    10
    Sunday
    February
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Hanna Rapaport
    Organizer: Department of Materials and Interfaces
    Abstract: Peptides in -sheet conformations have been developed in our lab in a bottom u ...Peptides in -sheet conformations have been developed in our lab in a bottom up fashion towards various biomedical applications. Hydrogels of -sheet peptides will be briefly introduced and the talk will then focus on peptide coatings for induced osseointegration of titanium implants and peptides enhanced nanoparticles for intracellularly targeted drug delivery.

    Chemical and Biological Physics Guest Seminar

    Date:
    10
    Sunday
    February
    2019
    Lecture / Seminar
    Time: 09:30
    Title: Computational Modeling of Large Biomolecular Systems: Methodology and a Case ‎Study of the Smartest Molecule (an NMDA Receptor in the Brain)
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Anton V. Sinitskiy
    Organizer: Department of Chemical and Biological Physics
    Abstract: In this talk targeted at a wide audience of chemists, I will start with a story ...In this talk targeted at a wide audience of chemists, I will start with a story about the ‘smartest’ molecule. Neuronal NMDA receptors, in my opinion, deserve this name, because they play the key role in the molecular mechanisms of learning, memory formation, and abstract reasoning. Also, malfunctioning NMDA receptors are involved in numerous neurological disorders, including schizophrenia, epilepsy, and Alzheimer’s disease. NMDA receptors are complicated and rich in behavior, and even the most up-to-date experimental methods yield only a fragmented picture of these biomolecules. How do their known structures relate to their biologically relevant functional states? Through what mechanisms do post-translational modifications (specifically, glycosylation) affect their physiological properties? Computational modeling offers unique insights into these questions, and I will outline my work in this field. Simulating NMDA receptors is a formidable task, though. In the second half of my talk, I will discuss how advances in methodology could facilitate studies of such large molecular and biomolecular systems. Specifically, I will focus on the concepts of coarse-graining, Markov state modeling, and mixed-resolution hybrid modeling, highlighting my work in this field [including ultra-coarse-grained modeling, and quantum mechanics / coarse-grained molecular mechanics (QM/CG-MM) approach]. Finally, I will briefly touch on the possible use of machine learning and deep learning networks in molecular modeling. In general, further advances in the theory and methodology of modeling will result in new opportunities for studying complex phenomena, such as learning and memory, with unprecedented resolution.

    Frustrations in the treatment of Ovarian Cancer

    Date:
    07
    Thursday
    February
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Special Guest Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Uziel Beller
    Organizer: Department of Biological Regulation

    Extension of in-situ nanoindentation results by (S)TEM graphical data processing

    Date:
    06
    Wednesday
    February
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Vasily A. Lebedev
    Organizer: Department of Materials and Interfaces
    Abstract: Nanomechanical measurements allow us to determine mechanical characteristics o ... Nanomechanical measurements allow us to determine mechanical characteristics of nano- and microobjects, which is required for further calculations of the mechanical parameters of the structures based on them. At the same time, in-situ measurements are carried out in the SEM and TEM chambers. Thus, it is possible to acquire graphic information that can supplement the indentation data. In this work, indentation of titania microspheres with different phase composition was tested by MEMS-based Hysitron PI-95 at Zeiss Libra 200MC TEM. Evaluation of the mechanical properties of microspheres in the elastic region was made according to the Hertz model. It turned out that annealing of the amorphous titania leads to an increase in the Young modulus, whereas the hydrothermal treatment reduces it from 27 to 4 Gpa. The differences in the destruction process was demonstrated for these kinds of particles. It has been shown, that hydrothermal treatment of titania microspheres leads to the formation of a reticular internal structure, whereas annealing results in sintering of the internal structure of microspheres. In the process of indentation, corresponding videos were also recorded, including the probe approach, indentation, and destruction of the microspheres. In order to process the videos we coded the program based on free Python packages. Using the Digital Image Correlation (DIC) algorithm, relative probe displacements were measured during indentation (Fig. 1a). The results obtained allowed us to clarify the calibration of the movement of the indenter in free sample tests, as well as to determine the drift function in real measurements. These results are important for long-term measurements, in particular creep tests. Based on graphical data we were able to determine the evolution of the shape of indented microspheres. During the video processing, areas of individual objects were determined, sizes of contact areas were calculated, and changes in linear dimensions of the deformed objects were determined (Fig. 1b). Therefore, a large amount of quantitative data was obtained from electron microscopy images. Fig.1 Illustration of probe displacement determination (a) and the shape evolution analysis

    The molecular mechanism of Respiratory Syncytial virus assembly

    Date:
    05
    Tuesday
    February
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Dr. Monika Bajorek
    Organizer: Department of Structural Biology

    Towards a new understanding of disorder and dissipation in solids

    Date:
    04
    Monday
    February
    2019
    Lecture / Seminar
    Time: 14:15
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Alessio Zaccone
    Organizer: Department of Physics of Complex Systems
    Abstract: Solid-state theory has been formulated in the 20th century on the assumptions of ...Solid-state theory has been formulated in the 20th century on the assumptions of regular crystalline lattices where linear dynamics holds at both classical and quantum levels, while dissipative effects are taken into account to perturbative order. While considerable success has been achieved in the further understanding of disorder effects on the electronic properties of solids, the same is not true for the thermal, vibrational and mechanical properties due to the difficulty of reformulating the whole body of lattice dynamics in a non-perturbative way for disordered systems. I will present a formulation of lattice dynamics extended (in a non-perturbative way) to disordered systems, called Nonaffine Lattice Dynamics (NALD), successfully tested on different systems [1-3]. I will then consider the effect of viscous dissipation on the lattice dynamics of crystalline solids and show how dissipation can lead, in perfectly ordered crystals, to effects very similar to disorder-induced effects in glasses. Theory can explain all these surprising effects in perfect crystals as a result of anharmonic damping inducing diffusive modes that compete with propagating modes [4], and also predicts similar effects resulting from low-lying soft optical phonons (experimentally confirmed). This framework may lead to a new quantitative connection between lattice/atomic parameters, electron-phonon coupling and the Tc of superconductors with the possibility, in future work, of rationalizing a variety of experimental data and to provide a more quantitative (less empirical) understanding of how Tc can be varied in conventional and perhaps also more exotic superconductors. [1] A. Zaccone and E. Scossa-Romano, Phys. Rev. B 83, 184205 (2011). [2] R. Milkus and A. Zaccone, Phys. Rev. B 93, 094204 (2016). [3] V.V. Palyulin, C. Ness, R. Milkus, R.M. Elder, T.W. Sirk, A. Zaccone, Soft Matter 14, 8475 (2018). [4] M. Baggioli and A. Zaccone, arXiv:1810.09516v1 [cond-mat.soft].

    Towards a new understanding of disorder and dissipation in solids

    Date:
    04
    Monday
    February
    2019
    Lecture / Seminar
    Time: 14:15
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Alessio Zaccone
    Organizer: Department of Physics of Complex Systems
    Abstract: Solid-state theory has been formulated in the 20th century on the assumptions of ...Solid-state theory has been formulated in the 20th century on the assumptions of regular crystalline lattices where linear dynamics holds at both classical and quantum levels, while dissipative effects are taken into account to perturbative order. While considerable success has been achieved in the further understanding of disorder effects on the electronic properties of solids, the same is not true for the thermal, vibrational and mechanical properties due to the difficulty of reformulating the whole body of lattice dynamics in a non-perturbative way for disordered systems. I will present a formulation of lattice dynamics extended (in a non-perturbative way) to disordered systems, called Nonaffine Lattice Dynamics (NALD), successfully tested on different systems [1-3]. I will then consider the effect of viscous dissipation on the lattice dynamics of crystalline solids and show how dissipation can lead, in perfectly ordered crystals, to effects very similar to disorder-induced effects in glasses. Theory can explain all these surprising effects in perfect crystals as a result of anharmonic damping inducing diffusive modes that compete with propagating modes [4], and also predicts similar effects resulting from low-lying soft optical phonons (experimentally confirmed). This framework may lead to a new quantitative connection between lattice/atomic parameters, electron-phonon coupling and the Tc of superconductors with the possibility, in future work, of rationalizing a variety of experimental data and to provide a more quantitative (less empirical) understanding of how Tc can be varied in conventional and perhaps also more exotic superconductors. [1] A. Zaccone and E. Scossa-Romano, Phys. Rev. B 83, 184205 (2011). [2] R. Milkus and A. Zaccone, Phys. Rev. B 93, 094204 (2016). [3] V.V. Palyulin, C. Ness, R. Milkus, R.M. Elder, T.W. Sirk, A. Zaccone, Soft Matter 14, 8475 (2018). [4] M. Baggioli and A. Zaccone, arXiv:1810.09516v1 [cond-mat.soft].

    Special Seminar Dr. Sylvia Cremer- Social immunity: protecting the superorganism against disease

    Date:
    04
    Monday
    February
    2019
    Lecture / Seminar
    Time: 13:00-14:00
    Location: Wolfson Building for Biological Research
    Lecturer: Sylvia Cremer
    Organizer: Department of Immunology
    Details: Social insects form societies of highly interactive members. Like in all social groups, infectious disease can use their hosts' social interaction routes to quickly spread among colony members. Yet, epidemics are very rare in insect societies, due to their highly sophisticated cooperative disease defenses, forming from a combination of behavioral, organizational, and physiological adaptations. In contrast to most other social groups, however, group members in insect colonies are not equal. Instead, they fall into two distinct groups, the reproductive caste (the queens and males) and the sterile caste (the workers). Insect colonies are hence often referred to as a superorganism, in analogy to multicellular organisms that are similarly separated into the reproductive organs, the germline, and the somatic body tissues. Selection pressures on insect colonies hence resemble that of individual organisms, and the social immune system of the colony acts surprisingly similar to the physiological immune system in our own bodies.

    Microstructural MRI: beyond the Standard Model

    Date:
    03
    Sunday
    February
    2019
    Lecture / Seminar
    Time: 16:30-17:30
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Noam Shemesh
    Organizer: Department of Materials and Interfaces
    Abstract: Despite the importance of tissue microstructure in health and disease, its nonin ...Despite the importance of tissue microstructure in health and disease, its noninvasive characterization remains a formidable challenge. Signal representations (diffusion/kurtosis tensors) are unspecific while tissue modelling using ideal geometries representing different cellular components have failed when scrutinized vis-à-vis histology: axon diameter, for example, is overestimated by factors of >6. Biophysical models characterizing signal behavior in specific diffusion-weighting regimes (power law scaling in “q” or “t”) have been more recently proposed as more reliable means for characterizing tissues. In recent years, the most prevalent biophysical model for diffusion in tissues was termed the “Standard Model”, consisting of a sum of gaussian components (nearly always two), one of which with zero diffusivity (stick). In the lecture, we will present validity regimes for the standard model and provide evidence for its limits. We will then propose a few novel means for characterizing

    Thesis defence presentation by Dr. Rotem Gidron-Budovsky (Reisner's Lab)

    Date:
    03
    Sunday
    February
    2019
    Lecture / Seminar
    Time: 12:00-13:00
    Title: “Immune tolerance induction by veto cells in bone marrow transplantation and in cell therapy .”
    Location: Wolfson Building for Biological Research
    Lecturer: Dr. Rotem Gidron-Budovsky
    Organizer: Department of Immunology

    Diabesity-induced Chronic Kidney Disease: When Kidneys Get the Munchies

    Date:
    27
    Sunday
    January
    2019
    Lecture / Seminar
    Time: 15:00-16:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Yossi Tam
    Organizer: Life Sciences

    Diabesity-induced Chronic Kidney Disease: When Kidneys Get the Munchies

    Date:
    27
    Sunday
    January
    2019
    Lecture / Seminar
    Time: 15:00-16:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Yossi Tam
    Organizer: Life Sciences

    Gain Fat - Lose Metastasis: From cancer cell plasticity to differentiation theraphy

    Date:
    24
    Thursday
    January
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Special Guest Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Dana Ishay Ronen
    Organizer: Department of Biological Regulation

    Thesis defence presentation by Guy Ledergor (AmitLab)

    Date:
    24
    Thursday
    January
    2019
    Lecture / Seminar
    Time: 08:30-10:00
    Title: “Single cell analysis of multiple myeloma and its precursor disease.”
    Location: Wolfson Building for Biological Research
    Lecturer: Guy Ledergor
    Organizer: Department of Immunology

    Special Guest Seminar with Prof. Joel S. Bader

    Date:
    23
    Wednesday
    January
    2019
    Lecture / Seminar
    Time: 14:00
    Title: “Identifying drivers of breast cancer metastasis”
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Joel S. Bader
    Organizer: The Kahn Family Research Center for Systems Biology of the Human Cell
    Abstract: Most breast cancer deaths are from metastasis, rather than growth of the primary ...Most breast cancer deaths are from metastasis, rather than growth of the primary tumor. Therapies for reducing deaths from metastatic cancer are limited, in part because much of the basic biology of metastasis remains unknown. We are developing and applying methods to identify these basic mechanisms. We describe work with experimental and clinical partners using organoids, clusters of 300-500 primary mammary cells, to interrogate metastasis-related phenotypes. We present new mathematical image processing methods that convert organoid images into quantitative invasion phenotypes. We then discuss genes and pathways whose activities lead to invasion, dissemination, and metastasis. Often the driver and effector genes are poor candidates for therapeutic intervention, but signaling intermediates can be targeted. We are prioritizing intermediates using new methods that characterize the density of paths through a biological network. We are recruiting women with breast cancer to participate in these studies as part of our US NCI Cancer Target Discovery & Development (CTD2) Center.

    Connecting the dots: functional and structural insights into the Legionella pneumophila Dot/Icm secretion system

    Date:
    22
    Tuesday
    January
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. David Chetrit
    Organizer: Department of Biomolecular Sciences
    Abstract: Type IV secretion systems (T4SS) are widespread in bacteria and despite their fu ...Type IV secretion systems (T4SS) are widespread in bacteria and despite their fundamental importance in processes such as DNA conjugation and pathogenesis of plants, animals and humans, they are among the most complex and yet arguably the least understood secretion systems in the prokaryotic kingdom. Using live fluorescence microscopy in conjunction with cryo-electron tomography, we determined the in-situ structure of the T4SS of the respiratory pathogen Legionella pneumophila, called Dot/Icm. Unexpectedly, we have discovered that the major ATPases energizing center in the cytosol of the bacterial cell creates a dynamic assembly and forms a unique central channel in that it is constructed by a hexameric array of dimeric proteins. We have showed that the ATPase DotB cycles between the cytosol and the Type IV machine, indicating that it is involved in energizing the Type IV apparatus once a signal is received to initiate protein translocation. Our data changed the existing paradigm for how T4SS function and provides new insights for future studies that are important for a complete understanding of host pathogen interaction processes.

    IMM Guest seminar-Prof. Yoram Reiter will lecture on "Engineering Immune Effector Molecules and Cells for Immunotherapy of Cancer and Autoimmunity."

    Date:
    21
    Monday
    January
    2019
    Lecture / Seminar
    Time: 13:00
    Location: Wolfson Building for Biological Research
    Lecturer: Prof. Yoram Reiter
    Organizer: Department of Immunology

    On cholesterol crystal formation from lipid membranes in relation to atherosclerosis

    Date:
    13
    Sunday
    January
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Lia Addadi
    Organizer: Department of Materials and Interfaces
    Abstract: Atherosclerosis causes heart attack and stroke and is a major fatal disease in t ...Atherosclerosis causes heart attack and stroke and is a major fatal disease in the Western world. The formation of atherosclerotic plaques in the artery walls is the result of LDL particle uptake, and consequently of cholesterol accumulation in macrophage cells. Excess cholesterol accumulation eventually results in cholesterol crystal deposition, the hallmark of mature atheromas. We study the formation of cholesterol monohydrate crystal polymorphs on lipid bilayer membranes and in cells enriched with cholesterol. This work may provide information on the crystal growth mechanisms involved, once the factors that favor the formation of different structures are understood

    Breeding has increased the diversity of cultivated tomato

    Date:
    08
    Tuesday
    January
    2019
    Lecture / Seminar
    Time: 11:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Henk J. Schouten
    Organizer: Department of Plant and Environmental Sciences
    Details: Host: Prof. Avraham Levy
    Abstract: Abstract: In view of the importance of biodiversity of crops for sustainable agr ...Abstract: In view of the importance of biodiversity of crops for sustainable agriculture, we studied the diversity dynamics of tomato varieties over the last seven decades. The genetic diversity was very low during the 1960s, but is now nine times higher when compared to that dip. The pressure since the 1970s to apply less pesticides led to the introgression of many disease resistances from wild relatives, representing the first boost of genetic diversity. In Europe a second boost ensued, largely driven by German popular media who named poor tasting tomatoes Wasserbomben (water bombs). The subsequent collapse of Dutch tomato exports to Germany fueled breeding for fruit flavor, further increasing diversity since the 1990s. Our study provides compelling evidence that breeding has increased the diversity of tomato varieties considerably.

    Universal features in disordered solids: Implications for directed aging and the creation of non-linear metamaterials

    Date:
    07
    Monday
    January
    2019
    Lecture / Seminar
    Time: 14:15
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Daniel Hexner
    Organizer: Department of Physics of Complex Systems
    Abstract: The most obvious and distinctive feature of an amorphous solid is its heterogene ...The most obvious and distinctive feature of an amorphous solid is its heterogeneous microscopic structure. A central issue is how such disorder governs the elastic properties of an amorphous solid so that it has different behavior from its crystalline counterpart. I will show how such disorder on the microscale determines the elastic properties on long length scales. This theoretical approach ultimately allows us to control a material’s elastic properties and to understand how a material ages and stores memories. I start by studying the change in an amorphous solid’s elastic properties upon the removal of a single bond. I show that the change in moduli, which has a broad and universal shape, is uncorrelated for different imposed strains. Thus, by selectively removing a small number of bonds, the precise global and local elastic behavior of the solid can be controlled. This in turn suggests that small changes in bond properties, which occur naturally as a solid ages, can dramatically alter the solid’s elastic response; the history of imposed strains is encoded in the non-linear response and the aging process, usually considered to be detrimental, can be harnessed to design materials with novel desired properties.

    IMM Guest seminar- Prof. Tal Burstyn-Cohen will lecture on "Myeloid-derived PROS1 Inhibits Tumor Metastasis by Curbing Inflammation."

    Date:
    07
    Monday
    January
    2019
    Lecture / Seminar
    Time: 13:00-14:00
    Location: Wolfson Building for Biological Research
    Lecturer: Prof. Tal Burstyn-Cohen
    Organizer: Department of Immunology

    Large-scale genomic investigations of psychiatric and neurodevelopmental disorders and their connection to somatic disease in the Danish population

    Date:
    07
    Monday
    January
    2019
    Lecture / Seminar
    Time: 10:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Ron Nudel
    Organizer: Department of Molecular Genetics
    Details: Denmark is one of a few countries which operate several public registries and biobanks, offering unique opportunities for population-level genomic studies. My talk will describe studies aiming at a better understanding of the molecular basis of psychiatric and neurodevelopmental disorders. I will present two of my studies which found strong links between infection, immunity and psychiatric disorders. The first study examined genetic correlations between susceptibility to severe infection and several psychiatric phenotypes such as schizophrenia, autism spectrum disorder, ADHD, anorexia, bipolar disorder and depression. The second study examined the possible connection between immune genes and the above disorders, highlighting a new candidate gene for a severe comorbid diagnosis of autism spectrum disorder and intellectual disability. Additionally, recent findings from the work led by colleagues at the Institute for Biological Psychiatry will also be presented; this will include a study of the genetic underpinnings of suicidal behavior in individuals with or without psychiatric disorders, which highlighted variants that were either in PDE4B, a known depression candidate gene, or in an enhancer from the GeneHancer database that likely regulates this gene, as well as a cross-disorder genetic investigation of psychiatric outcomes, highlighting a shared genetic etiology across major disorders. Lastly, I will provide a broad outline of this unique case-cohort study sample and our effective genetic analysis pipelines, which together offer exceptional opportunities and power to study psychiatric disorders, which are predicted to be one of the major disease burdens of the near future.

    Dissecting epithelial surfaces in health and disease

    Date:
    06
    Sunday
    January
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Moshe Biton
    Organizer: Department of Biological Regulation

    Medicinal Chemistry at The Weizmann Institute Who we are What we do to discover Chemical Probes

    Date:
    03
    Thursday
    January
    2019
    Lecture / Seminar
    Time: 09:00-10:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Chakrapani Subramanyam
    Organizer: Department of Life Sciences Core Facilities

    Neuro-Behavioral Constraints on the Acquisition and Generation of Motor Skills

    Date:
    01
    Tuesday
    January
    2019
    Lecture / Seminar
    Time: 14:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Dr. Maria Korman
    Organizer: Department of Neurobiology
    Details: Host: Prof. Rony Paz rony.paz@weizmann.ac.il tel: 6236 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: Acquisition of motor skills often involves the concatenation of single movements ...Acquisition of motor skills often involves the concatenation of single movements into sequences. Along the course of learning, sequential performance becomes progressively faster and smoother, presumably by optimization of both motor planning and motor execution. Following its encoding during training, “how-to” memory undergoes consolidation, reflecting transformations in performance and its neurobiological underpinnings over time. This offline post-training memory process is characterized by two phenomena: reduced sensitivity to interference and the emergence of delayed, typically overnight, gains in performance. Successful learning is a result of strict control (gating) over the on-line and off-line stages of the experience-driven changes in the brain’s organization (neural plasticity). Factors, such as the amount of practice, the passage of time and the affordance of sleep and factors specific to the learning environment may selectively affect, – block or accelerate, - the expression of delayed gains in motor performance. These factors interact in a complex, non-linear manner. Developmental and inter-individual differences impose additional constraints on memory processes (e.g., age, chronotype, clinical condition). High-level reorganization of the movements as a unit following practice was shown to be subserved by optimization of planning and execution of individual movements. Temporal and kinematic analysis of performance demonstrated that only the offline inter-movement interval shortening (co-articulation) is selectively blocked by the interference experience, while velocity and amplitude, comprising movement time, are interference–insensitive. Sleep, including a day-time sleep, reduces the susceptibility of the memory trace to retroactive behavioural interference and also accelerates the expression of delayed gains in performance. Activity in cortico-striatal areas that was disrupted during the day due to interference and accentuated in the absence of a day-time sleep is restored overnight. Additional line of experiments showed that on-line environmental noise during training (vibro-auditory task-irrelevant stimulation) may be an important modulator of memory consolidation; its impact is ambiguous, presumably contingent on baseline arousal levels of the individual. 1. Albouy G., King B. R., Schmidt C., Desseilles M., Dang-Vu T., Balteau E., Phillips C., Degueldre C., Orban P., Benali H., Peigneux P., Luxen A., Karni A., Doyon J., Maquet P., Korman M. 2016 Cerebral Activity Associated with Transient Sleep-Facilitated Reduction in Motor Memory Vulnerability to Interference Scientific Reports 6:34948 2. Friedman J., Korman M. 2016 Offline optimization of the relative timing of movements in a sequence is blocked by behavioral retroactive interference Frontiers in Human Neuroscience, 10:623 3. Korman M., Herling Z., Levy I., Egbarieh N., Engel-Yeger B., Karni A. 2017 Background matters: minor vibratory sensory stimulation during motor skill acquisition selectively reduces off-line memory consolidation. Neurobiology of Learning and Memory 140:27-32

    Dynamic self assembly of virus capsids

    Date:
    30
    Sunday
    December
    2018
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Uri Raviv
    Organizer: Department of Materials and Interfaces
    Abstract: The assembly and disassembly of virus capsids, composed of many subunits, are fu ...The assembly and disassembly of virus capsids, composed of many subunits, are fundamental steps in the viral life cycle. The complete set of possible capsid intermediates is immense, ~1030. Yet, the assembly process is done with high fidelity and leads to stable capsids that can efficiently encapsulate and protect genetic material, and when needed, dissociate and release their cargo. Virus capsids are therefore stable and flexible dynamic structures. To better understand and predict the outcomes of these apparently contradictory processes, we precisely analyzed the structure, kinetics, and thermodynamic stability of the experimentally tractable Hepatitis B virus assembly reaction, in vitro. High-resolution modern synchrotron solution X-ray scattering measurements of assembly reactions provided statistically reliable and rich structural data. We rigorously analyzed the data by integrating our home-developed state-of-the-art scattering data analysis software D+ (https://scholars.huji.ac.il/uriraviv/software/d-software) with simulations and theory of macromolecular self-assembly. Our accurate and comprehensive analysis provided new insight into the mechanisms of viral self-assembly and the boundaries where thermodynamic products can be realized and function, and when kinetically trapped metastable states may form. This insight could be important for designing antiviral therapeutics as well as noncapsules or nanoreactors

    Chemical and Biological Physics Guest Seminar

    Date:
    30
    Sunday
    December
    2018
    Lecture / Seminar
    Time: 09:30
    Title: New Frontiers in Membrane Biophysics
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Raya Sorkin
    Organizer: Department of Chemical and Biological Physics
    Abstract: Membranes compartmentalize living matter into cells and subcellular structures. ...Membranes compartmentalize living matter into cells and subcellular structures. Many life processes involve membrane topological changes and remodelling: the uptake of materials via endocytosis and secretion by exocytosis, the generation of intra or extra-cellular vesicles as well as various membrane fusion processes. In order to get to the bottom of these fundamental physiological processes, it is vital to study membrane mechanical properties and membrane deformation. In this talk I will present the results of our research on several aspects of vesicle generation and membrane fusion using single molecule techniques. By means of an AFM force spectroscopy study we characterized the mechanical properties of small natural vesicles, called extracellular vesicles (EVs). Investigating the mechanical properties of these vesicles and their lipid and protein content provided new insights into the still poorly understood processes underlying vesicle generation. Acoustic Force Spectroscopy (AFS) was the choice for our novel methodology to measure cell mechanical properties. It enabled our finding that uptake of EVs by cells changes cellular deformability, a process that may have implications in several disease states where EV levels are significantly elevated, such as malaria and breast cancer. Combining optical tweezers with confocal fluorescence microscopy was the perfect tool for the investigation of membrane remodelling by calcium sensor proteins which are crucial in neuronal communication. We discovered surprising differences between the action mechanisms of two structurally similar proteins, Doc2b and Synaptotagmin-1 (Syt1), as determined by quantifying the strength and probabilities of protein-induced membrane-membrane interactions. Overall these fundamentally new insights into central biological processes were possible by our biophysical characterization of membranes using a powerful combination of single molecule techniques: Optical tweezers combined with confocal fluorescent microscopy, AFS and AFM.

    Ca2+ stores in animal models of Alzheimer’s disease

    Date:
    27
    Thursday
    December
    2018
    Lecture / Seminar
    Time: 13:30-14:45
    Location: Nella and Leon Benoziyo Building for Brain Research
    Lecturer: Etay Aloni (PhD Thesis Defense)
    Organizer: Department of Neurobiology
    Abstract: : Intracellular Ca2+ concentration ([Ca2+]i) is tightly regulated in neurons. Ca ...: Intracellular Ca2+ concentration ([Ca2+]i) is tightly regulated in neurons. Ca2+ plays important roles in signal transduction pathways, synaptic plasticity, energy metabolism and apoptosis. In dendritic spines, [Ca2+]i is controlled by voltage and ligand-gated channels that allow Ca2+ entry from the extracellular space and by ryanodine receptors (RyR) and inositol 1,4,5-trisphosphate receptors (IP3R) that release Ca2+ from intracellular stores. Disruption in Ca2+ homeostasis is linked to several pathologies and is suggested to play a pivotal role in the cascade of events leading to Alzheimer disease (AD). In line with this, I found that low concentrations of caffeine, known to release Ca2+ from stores, is more effective in facilitating long-term potentiation (LTP) induction in hippocampal slices of a triple-transgenic (3xTg) mouse model of AD than controls. Synaptopodin (SP) is a protein residing in the dendritic spines. SP is an essential component in the formation of the spine apparatus (SA), which is a specialized form of smooth endoplasmic reticulum (ER) found in dendritic spines. Spines lacking SP were shown to release less Ca2+ from stores. The present study is aimed to explore the involvement of Ca2+ stores in 3xTg mouse model of AD. By crossing 3xTg and SPKO mice lines, I studied the effect of SP deficiency on AD markers in the 3xTg mouse. I found that the 3xTg/SPKO mice show normal learning in a spatial memory task by comparison to the deficiency found in the 3xTg mouse, and express normal LTP in hippocampal slices, which is deficient in 3xTg mice. Furthermore, low concentration of ryanodine has a facilitating effect on LTP induction only in the 3xTg mice group. In addition, these brains do not express amyloid plaques, activated microglia, p-tau overexpression and high RyR expression seen in age matched 3xTg mice, These results suggest that SP deficiency restores [Ca2+]i homeostasis in the 3xTg so as to suppress the progression of AD symptoms.

    Spotlight on Science

    Date:
    26
    Wednesday
    December
    2018
    Lecture / Seminar
    Time: 12:00
    Title: The Dynamics of brain development in health and disease
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Dr. Tamar Sapir

    Chemical and Biological Physics Special Seminar

    Date:
    25
    Tuesday
    December
    2018
    Lecture / Seminar
    Time: 10:45
    Title: Cell-Matrix Interactions in Fibrosis and Cancer: Multiscale mechano-chemical models
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Vivek Shenoy
    Organizer: Clore Center for Biological Physics
    Abstract: Much of our understanding of the biological mechanisms that underlie cellular fu ...Much of our understanding of the biological mechanisms that underlie cellular functions, such as migration, differentiation and force sensing has been garnered from studying cells cultured on two-dimensional (2D) substrates. In the recent years there has been intense interest and effort to understand cell mechanics in three-dimensional (3D) cultures, which more closely resemble the in vivo microenvironment. However, a major challenge unique to 3D settings is the dynamic feedback between cells and their surroundings. In many 3D matrices, cells remodel and reorient local extracellular microenvironment, which in turn alters the active mechanics and in many cases, the cell phenotype. Most models for matrices to date do not account for such positive feedback. Such models, validated by experiments, can provide a quantitative framework to study how injury related factors (in pathological conditions such as fibrosis and cancer metastasis) alter extracellular matrix (ECM) mechanics. They can also be used to analyze tissue morphology in complex 3D environments such as during morphogenesis and organogenesis, and guide such processes in engineered 3D tissues. In this talk, I will present discrete network simulations to study how cells remodel matrices and how this remodeling can lead to force transmission over large distances in cells. I will also discuss an active tissue model to quantitatively study the influence of mechanical constraints and matrix stiffness on contractility and stability of micropatterned tissues.

    Novel insights into the structure and function of microbial communities

    Date:
    25
    Tuesday
    December
    2018
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Ilana Kolodkin
    Organizer: Department of Biomolecular Sciences
    Abstract: In nature, bacteria form differentiated multicellular communities, known as biof ...In nature, bacteria form differentiated multicellular communities, known as biofilms. The coordinated actions of many cells, communicating and dividing labor, improve the ability of the community to attach to hosts and protect it from environmental assaults.Bacterial biofilms are associated with persistent bacterial infections, and thus pose a global threat of extreme clinical importance. Bacteria in a biofilm are significantly more resistant to antibiotics than free-living bacteria. Our work provides two novel explanations of this phenotypic antibiotic resistance: a structural mineral component defending the bacterial colony, and the ability of community members to communicate and coordinate activities using RNA transfer.

    Imm Guest seminar-Shai Shen-Orr will lecture on "Cellular variability in the immune system. Where are we going and how did we get here"

    Date:
    24
    Monday
    December
    2018
    Lecture / Seminar
    Time: 13:00-14:00
    Location: Wolfson Building for Biological Research
    Lecturer: Shai Shen-Orr
    Organizer: Department of Immunology

    Imm Special Guest Seminar:Dr. Moshe Biton ,will lecture about "Exploring epithelial-immune cell interactions of mucosal surfaces in health and disease”

    Date:
    20
    Thursday
    December
    2018
    Lecture / Seminar
    Time: 00:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Moshe Biton
    Organizer: Department of Immunology

    Translational control of cancer and neurological disease via eIF4E

    Date:
    18
    Tuesday
    December
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Nahum Sonenberg
    Organizer: Department of Structural Biology

    Global outbreaks: Interferons as 1st responders

    Date:
    18
    Tuesday
    December
    2018
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Eleanor N. Fish
    Organizer: Department of Biomolecular Sciences
    Abstract: Emerging and re-emerging virus infections pose a threat to global health. Viruse ...Emerging and re-emerging virus infections pose a threat to global health. Viruses mutate to inevitably evade the effects of pathogen-specific antivirals, and the time required to develop a vaccine specific for an outbreak virus leaves populations unprotected for months. Our strategy is to focus on broad spectrum antivirals for diverse acute virus infections: interferons (IFNs)-. IFNs- exert both direct antiviral effects in infected cells and modulate host immune responses to clear virus. Data will be presented providing evidence for the antiviral effects of IFNs-against influenza A viruses H5N1 and pandemic H1N1, the SARS coronavirus and ebola virus, in vitro and in clinical studies during outbreaks. The mechanisms whereby IFNs-exert their antiviral effects and override the inhibitory effects of viruses will be described.

    Remodelling of the vasculature in cardiovascular disease

    Date:
    16
    Sunday
    December
    2018
    Lecture / Seminar
    Time: 13:00-14:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Andrew Baker
    Organizer: Department of Biological Regulation

    Sela Symposium 2018

    Date:
    16
    Sunday
    December
    2018
    Lecture / Seminar
    Time: 09:00-12:00
    Title: B cell and Antibody biology – from basics to therapy
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Michel Nussenzweig and Prof. Jeffrey V. Ravetch
    Organizer: Department of Immunology

    Joint mini-symposium

    Date:
    13
    Thursday
    December
    2018
    Lecture / Seminar
    Time: 11:00-13:00
    Title: Joel Richter will lecture on "Translational Control of Neurological Disease" Le Ma will lecture on "Molecular and Cellular Mechanisms of Axonal Branch Development"
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Joel Richter
    Organizer: Department of Molecular Genetics

    Chemical and Biological Physics and The Clore Center for Biological Physics Seminar

    Date:
    12
    Wednesday
    December
    2018
    Lecture / Seminar
    Time: 13:00
    Title: Biological Tissues as Active Materials
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. M. Cristina Marchetti
    Organizer: Clore Center for Biological Physics
    Abstract: The mechanical properties of dense tissues control many biological processes, fr ...The mechanical properties of dense tissues control many biological processes, from wound healing to embryonic development to cancer progression. In this talk I will discuss recent theoretical work that combines developmental models with active matter physics to describe dense tissue as active materials that exhibit a jamming-unjamming transition tuned by cell shape and cell motility. Cell division and death, as well as mechanical feedback that coordinates cell migration, can modify the transition resulting in novel tissue ``materials’’ properties. These findings may have implications for cell sorting and patterning in wound healing and development.

    “Diffusion NMR of out-of-equilibrium mixtures”

    Date:
    11
    Tuesday
    December
    2018
    Lecture / Seminar
    Time: 09:30
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Jean-Nicolas Dumez
    Organizer: Department of Materials and Interfaces
    Abstract: The NMR spectra of molecular species in solution mixtures can be separated wit ... The NMR spectra of molecular species in solution mixtures can be separated with diffusion-ordered NMR spectroscopy (DOSY), a ‘virtual chromatography’ approach based on the measurement of translational diffusion coefficients. Classic DOSY experiments, however, require several minutes are not applicable to many important time-evolving mixtures. Taking advantage of the concept of spatial encoding, we show here that DOSY data can be collected in a single scan of less than one second for several types of out-of-equilibrium mixtures. SPEN provides an acceleration of DOSY experiments by several orders of magnitude. SPEN DOSY pulse sequences are developed, that compensate for convection effects and are suitable for measurements in low-viscosity organic solvents, a requirement to monitor organic chemical reactions. We also show how to collect multiple consecutive scans from short-lived, non-renewable signals produced by dissolution dynamic nuclear polarisation (D-DNP), which is a versatile and powerful hyperpolarisation method. These methodological developments are supported by advanced numerical simulations, based on a Fokker-Plank formalism to describe simultaneously the spin and spatial dynamics. An exemple of hyperpolarised sample is given with a model mixture of small molecules, while the ability to monitor a reacting mixture is illustrated with a diamination reaction in dichloromethane. The proposed UF DOSY methodology may contribute towards a real-time diffusion NMR analysis of mixtures, to help in the identification of a sample’s components and in the analysis of molecular interactions.

    “Diffusion NMR of out-of-equilibrium mixtures”

    Date:
    11
    Tuesday
    December
    2018
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Jean-Nicolas Dumez
    Organizer: Department of Materials and Interfaces
    Abstract: The NMR spectra of molecular species in solution mixtures can be separated with ...The NMR spectra of molecular species in solution mixtures can be separated with diffusion-ordered NMR spectroscopy (DOSY), a ‘virtual chromatography’ approach based on the measurement of translational diffusion coefficients. Classic DOSY experiments, however, require several minutes are not applicable to many important time-evolving mixtures. Taking advantage of the concept of spatial encoding, we show here that DOSY data can be collected in a single scan of less than one second for several types of out-of-equilibrium mixtures. SPEN provides an acceleration of DOSY experiments by several orders of magnitude. SPEN DOSY pulse sequences are developed, that compensate for convection effects and are suitable for measurements in low-viscosity organic solvents, a requirement to monitor organic chemical reactions. We also show how to collect multiple consecutive scans from short-lived, non-renewable signals produced by dissolution dynamic nuclear polarisation (D-DNP), which is a versatile and powerful hyperpolarisation method. These methodological developments are supported by advanced numerical simulations, based on a Fokker-Plank formalism to describe simultaneously the spin and spatial dynamics. An exemple of hyperpolarised sample is given with a model mixture of small molecules, while the ability to monitor a reacting mixture is illustrated with a diamination reaction in dichloromethane. The proposed UF DOSY methodology may contribute towards a real-time diffusion NMR analysis of mixtures, to help in the identification of a sample’s components and in the analysis of molecular interactions.

    Small Molecule Inhibitors of Breast Cancer

    Date:
    10
    Monday
    December
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Nira Ben-Jonathan
    Organizer: Department of Biological Regulation

    TBA

    Date:
    10
    Monday
    December
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Nira Ben Jonathan
    Organizer: Department of Biological Regulation

    Prof. Michal Schwartz - Will Immunotherapy defeat Alzheimer’s disease?

    Date:
    04
    Tuesday
    December
    2018
    Lecture / Seminar
    Time: 12:00-13:00
    Title: Will Immunotherapy defeat Alzheimer’s disease?
    Location: Dolfi and Lola Ebner Auditorium
    Lecturer: Prof. Michal Schwartz
    Organizer: Department of Media Relations
    Details: The lecture is in Hebrew

    Prof. Michal Schwartz - Will Immunotherapy defeat Alzheimer’s disease?

    Date:
    04
    Tuesday
    December
    2018
    Lecture / Seminar
    Time: 12:00
    Title: Will Immunotherapy defeat Alzheimer’s disease?
    Location: Dolfi and Lola Ebner Auditorium
    Lecturer: Prof. Michal Schwartz
    Organizer: Department of Media Relations
    Details: The lecture is in Hebrew

    Prof. Michal Schwartz - Will Immunotherapy defeat Alzheimer’s disease?

    Date:
    04
    Tuesday
    December
    2018
    Lecture / Seminar
    Time: 12:00
    Title: Will Immunotherapy defeat Alzheimer’s disease?
    Location: Dolfi and Lola Ebner Auditorium
    Lecturer: Prof. Michal Schwartz
    Organizer: Department of Media Relations
    Details: The lecture is in Hebrew

    Photostimulated physico-chemical processes at semiconductor / polyelectrolyte interface to further brain-inspired computing

    Date:
    04
    Tuesday
    December
    2018
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Prof. Ekaterina V. Skorb
    Organizer: Department of Organic Chemistry
    Abstract: Processes at the interface of inorganic solids and polymers mimic a large variet ...Processes at the interface of inorganic solids and polymers mimic a large variety of natural processes such as stimuli responsive behavior, self-healing, actuation, transport and delivery, pH-buffering, but they are not well understood. Polyelectrolyte multilayers are suitable for studying this, as they can be manipulated at will between glassy, rubbery, hydrogel or organogel. We suggest to investigate photocatalytically triggered local pH changes in titania / polyelectrolyte Layer-by-Layer (LbL) / lipid bilayer assembled interfaces, mimicking natural processes in a novel design strategy for inorganic / polymer interfaces as well as to further brain-inspired computing. We have shown recently that under irradiation of TiO2 a series of photocatalytic reactions leads to a local change in pH, which modulates the pH sensitive LbL assembly. Prime questions are: (i) how many photons are needed to locally change the pH on titania? (ii) what is the optimum LbL architecture to understand the basis of proton trapping and storage, the pH gradient under local irradiation? And (iii) how to achieve reversible actuation of different assemblies for advanced applications? We focus for the first time on the possibility of efficient transformation of energy of electromagnetic irradiation into local pH shift to actuate soft matter. This is used to demonstrate the application on cell surface interactions, self-repairing strategies, use of a chemical systems to communicate with bacteria, in general control on non-linear chemical processes at interfaces.

    Co-translational protein folding and quality control, in health and disease

    Date:
    04
    Tuesday
    December
    2018
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Ayala Shiber
    Organizer: Department of Biomolecular Sciences
    Abstract: The folding of newly synthesized proteins to the native state is a major challen ...The folding of newly synthesized proteins to the native state is a major challenge in the crowded cytoplasm. Failure to achieve the native fold often leads to aggregation, characteristic of neurodegenerative diseases. At the critical intersection of translation and folding, the ribosome is emerging as a hub, guiding the folding of the emerging polypeptide-chain. However, little is known about the final step of folding, the assembly of polypeptides into oligomeric complexes. Here we provide a systematic and mechanistic analysis of protein complex assembly in eukaryotes. We used a ribosome profiling approach to determine the in vivo interactions of various complexes of Saccharomyces cerevisiae, at near-codon resolution. We find co-translational assembly is a prevalent mechanism in eukaryotes. Assembly interactions protect the emerging polypeptide-chain from misfolding. Beyond assembly, we detect co-translational interaction networks within pathways. Thus, we find translation in eukaryotes is highly coordinated with folding, complex assembly and entire pathway formation.

    Advances in Drug Discovery

    Date:
    03
    Monday
    December
    2018
    -
    07
    Friday
    December
    2018
    Conference
    Time: 08:00
    Location: David Lopatie Conference Centre

    Exploring the Heart: from Genetic Mutations to Tissue Function

    Date:
    02
    Sunday
    December
    2018
    Lecture / Seminar
    Time: 13:00
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Anna Grosberg
    Organizer: Clore Center for Biological Physics
    Abstract: The heart is a fascinatingly efficient pump with intricate design criteria. Whil ...The heart is a fascinatingly efficient pump with intricate design criteria. While many aspects of heart function remain a mystery, investigations through the prism of mechanics, physics, and mathematics can provide invaluable insights – presented as three examples in this talk. First, we consider the problem of automatically characterizing cardiac tissue architecture over multiple length-scales. Through, the use of existing and creation of new order parameters, multiple discoveries were made such as the existence of consistently sized spontaneous patches of organization in isotropic cardiac tissues. Second, we explore the relationship between cell organization and tissue force generation. Through a tissue engineering trick, the global (~1mm) and local (~100 microns) architecture effects were separated, and it was discovered that the reduction in developed force due purely to changes in global tissue architecture can be predicted by an astonishingly simple physical model, while local changes trigger complex biological responses. Third, we investigate the relationship among genetic mutations to the nuclear lamina protein, Lamin A/C (LMNA), detrimental consequences to cellular architecture, and cardiac function. LMNA mutations can lead to a devastating early aging disease (progeria) or have a subtler effect with patients presenting only with heart disease symptoms. However, the mechanisms by which the LMNA mutation emerges in the heart muscle are unknown. Thus far we have uncovered a relationship between nuclear defects in patient-specific cells and the age at which these patients present with heart disease symptoms. Additionally, we have found that the pathology that takes decades to develop in patients can be recapitulated in a dish within a few weeks. Through all three of these examples, we will also explore newly generated mysteries that can again be elucidated in the future through the application of physical principles.

    Students’ and Post-docs’ Cancer Research Innovation Awards- presentation event

    Date:
    29
    Thursday
    November
    2018
    Lecture / Seminar
    Time: 09:00-12:00
    Location: Max and Lillian Candiotty Building
    Organizer: Department of Molecular Cell Biology

    A new way cancer cells cope with proteotoxic stress

    Date:
    28
    Wednesday
    November
    2018
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Peter Tsvetkov
    Organizer: Department of Biomolecular Sciences
    Abstract: Maintaining protein homeostasis is crucial for cell survival and coping with env ...Maintaining protein homeostasis is crucial for cell survival and coping with environmental stressors. The mechanisms that cells deploy to cope with increased proteotoxic burden are still poorly understood. In this work, using genetic screens, cancer genomics analysis and biochemical validations we determine a new way cancer cells can cope with increased proteotoxic burden. This mechanism involves two complementary cellular adaptations that are sufficient to promote cell survival when proteasome function is suppressed. These cellular adaptations are naturally occurring in many cancer types and evolutionary conserved and entail a vulnerability that can be targeted with a newly identified mitochondrial pathway inhibitor for which the unique mechanism of action we describe.

    Developmental Club Series 2018-2019

    Date:
    28
    Wednesday
    November
    2018
    Lecture / Seminar
    Time: 10:00
    Title: Modeling lymphatic development and disease in the zebrafish
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Nathan Lawson
    Organizer: Department of Molecular Genetics

    The simplicity within complexity of type 1 IFN signaling

    Date:
    27
    Tuesday
    November
    2018
    Lecture / Seminar
    Time: 10:30-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Victoria Urin
    Organizer: Department of Biomolecular Sciences
    Abstract: Type I interferons (IFN-1) are best known for their role in innate immunity, but ...Type I interferons (IFN-1) are best known for their role in innate immunity, but they are also involved in immunomodulation, proliferation, cancer surveillance, and the regulation of the adaptive immune response. How does the interaction of a cytokine with its receptors promote such diverse activities? To answer this question, I generated knockout (KO) HeLa cell lines and learned how these KOs affect different activities. The deletion of either STAT1 or STAT2 alone reduced, but did not eliminate IFN-1 induced activities. Conversely, the deletion of both completely abrogated any IFN-1 activity. So did the double STAT2-IRF1 KO, and a knockdown of IRF9 on background of STAT1 KO, suggesting the GAS pathway and the STAT2-IRF9 dimer as complimentary pathways to STAT1-STAT2. Interestingly, deletion of any of the mentioned components had no effect on the phosporylation of any of the other STATs including STAT3 and STAT6. To directly asses the importance of STAT3 in the system, I generates its KO, which had no effect on IFN-1 activation. Those evidence suggest that IFN-1 induced signaling goes only through STAT1 and STAT2, although not both are required.

    Exploring the dependence of HSF1’s transcriptional program in cancer stroma on the epigenome

    Date:
    27
    Tuesday
    November
    2018
    Lecture / Seminar
    Time: 10:00-10:15
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Coral Halperin
    Organizer: Department of Biomolecular Sciences
    Abstract: The tumor microenvironment (TME) has gained increasing attention in the last few ...The tumor microenvironment (TME) has gained increasing attention in the last few years, yet the exact mechanism by which the TME is reprogrammed to promote tumor phenotypes is not very clear. We have recently found that Heat shock factor 1 (HSF1) transcriptionally reprograms cancer associate fibroblasts (CAFs) in the TME towards a protumorigenic phenotype. HSF1 is a transcription factor that activates 3 different transcriptional programs in 3 different states of the cell - heat-shock, cancer cell and CAF. In this work I explore the hypothesis that a disparate DNA methylation or histone modification landscape results in differential access of HSF1 to the DNA, and leads to different transcriptional programs between cancer cells, CAFs and heat-shocked cells, by using bisulfite sequencing for establish a methylome profile of each cell states and Preform ChIP-seq with HSF1 antibodies in each type of cells to obtain the binding pattern of this TF in the different cells types/states. This work will provide a much-needed understanding on the epigenetic map of CAFs in the TME, which is currently lacking.

    Small Animal Brain Diffusion Imaging: From White Matter Evolution to Brain Disease Diagnosis

    Date:
    22
    Thursday
    November
    2018
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Hao Lei
    Organizer: Department of Materials and Interfaces
    Abstract: White matter (WM) plays a central role in the long-range connection and coordina ...White matter (WM) plays a central role in the long-range connection and coordinated communication between different brain regions. Diffusion magnetic resonance imaging (DMRI) uses the diffusion of water molecules as an endogenous probe to characterize WM microstructural integrity in and structural connectivity of the brain. The usefulness of DMRI in clinical settings and basic neuroscience research has been fully demonstrated. Our laboratory has been using DMRI and DMRI-based tractography to study normal and diseased brain of small animals (i.e., rodents and tree shrews) in the last ten years. In this talk, I will share some of these experiences, focusing on two stories. The first is the use of a super-resolution DMRI approach to reveal fine anatomical architecture in the brain of tree shew, and how the WM configuration in this squirrel-like mammal compared with the others on the evolutionary tree. The second is concerning the histological underpinning of dMRI changes in rat models of neurodegenerative diseases.

    Spotlight on Science

    Date:
    21
    Wednesday
    November
    2018
    Lecture / Seminar
    Time: 12:00
    Title: Single-Cell Genomics Reveals a Novel Regulatory Role of the Immune System in Obesity
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Diego Jaitin

    Cancer Volatolomics: From Evidence to Point-of-Care Diagnostics

    Date:
    15
    Thursday
    November
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Hossam Haick
    Organizer: Department of Biological Regulation
    Abstract: The current talk will present evidences that each cancer has its own unique vola ...The current talk will present evidences that each cancer has its own unique volatile molecular print and, therefore, the presence of one cancer would not screen out others. Based on this concept, a new generation of biomedical devices for achieving personalized diagnosis of various cancers in a noninvasive, inexpensive and portable manner via various body fluids (e.g., breath or skin) will be presented and discussed.

    Neurophysiology of States of Consciousness: From Mechanistic Principles to Novel Diagnostic and Therapeutic Tools

    Date:
    15
    Thursday
    November
    2018
    Lecture / Seminar
    Time: 12:30
    Location: Nella and Leon Benoziyo Building for Brain Research
    Lecturer: Prof. Jacobo Diego Sitt
    Organizer: Department of Neurobiology
    Details: Benoziyo Brain Research Building Room 113 Host: Prof. Noam Sobel noam.sobel@weizmann.ac.il tel: 6253 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: Uncovering the neural mechanisms that allow conscious access to information is a ...Uncovering the neural mechanisms that allow conscious access to information is a major challenge of neuroscience. An incomplete list of still open questions include, What are the necessary brain computational properties to permit access to a stream of conscious contents? What is the relationship between conscious perception, self-awareness and multisensory processing of bodily signals? How these processes change when the brain transitions to an ‘unconscious’ state (like sleep, anaesthesia or pathological conditions)? Can we externally trigger state-of-consciousness (SOC) transitions by means of stimulation? In this presentation I will present my work focus in these relevant scientific and clinical questions. I will present our latest developments including different pre-clinical and clinical experimental models (brain-injuries and/or anesthesia), neuroimaging methods (EEG, fMRI or brain/body interactions) and stimulation techniques (tES, auditory/somatosensory/visual stimulation). Overall I will try to demonstrate that the integration of multimodal neural information provides critical information to characterise the state-of-consciousness in physiological and pathological conditions and might help to predict novel optimal therapeutic strategies.

    Imm Special Guest Seminar:Dr. Tzachi Hagai ,will lecture about "Trapped between pathogens and autoimmunity: the evolution of our immune system ”

    Date:
    05
    Monday
    November
    2018
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Wolfson Building for Biological Research
    Lecturer: Dr. Tzachi Hagai
    Organizer: Department of Immunology

    DWEK Workshop on Children & Cancer

    Date:
    04
    Sunday
    November
    2018
    Lecture / Seminar
    Time: 08:00-17:00
    Title: See Conferences
    Location: Max and Lillian Candiotty Building
    Lecturer: Ayelet Erez and Yosef Yarden
    Organizer: Department of Biological Regulation

    Unravelling the tumor immune microenvironment by multiplexed imaging

    Date:
    28
    Sunday
    October
    2018
    Lecture / Seminar
    Time: 15:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Dr. Leeat Yankielowicz-Keren
    Organizer: Department of Immunology,Department of Molecular Cell Biology,Department of Molecular Genetics

    Development of placenta-derived (PLX) cell therapy- from bench- to bedside

    Date:
    25
    Thursday
    October
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Special Guest Lecture
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Racheli Ofir
    Organizer: Department of Biological Regulation
    Abstract: PLacental expanded (PLX) cells are placenta-derived, mesenchymal-like adherent s ...PLacental expanded (PLX) cells are placenta-derived, mesenchymal-like adherent stromal cells expanded using a bioreactor system which provides a three dimensional (3D) micro-environment enabling tightly controlled expansion. Accumulated data from multiple in vitro and in vivo experiments indicate that these cells act via a paracrine or endocrine manner to facilitate healing of damaged tissue. Pluristem’s two lead placenta-derived cell products, PLX-PAD and PLX-R18, are each in clinical development for several indications. PLX-Immune is in non-clinical development stages for Cancer. Data from non-clinical as well as clinical studies will be presented.

    Emotional valence and implicit memory formation under anesthesia: Neural mechanisms in the amygdala and pre-frontal cortex

    Date:
    24
    Wednesday
    October
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Nella and Leon Benoziyo Building for Brain Research
    Lecturer: Nir Samuel (PhD Thesis Defense)
    Organizer: Department of Neurobiology
    Details: Benoziyo Brain Research Building Room 113 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: Background: The aim of anaesthesia is to eliminate awareness and prevent memory ...Background: The aim of anaesthesia is to eliminate awareness and prevent memory of the various aversive stimuli of medical procedures. Yet in a portion of cases, patients can recall events that occurred during surgery resulting in risks of adverse psychological outcomes. Fear conditioning offers a robust behavioral model to study this phenomenon, while the abundant evidence implicating the amygdala-medial prefrontal cortex (mPFC) circuit in acquisition, consolidation and retrieval of these memories offers a natural hypothesis for the neural mechanisms. Objective: We aimed to study the effect of anaesthesia on stimulus valence, acquisition and memory and to identify the correlates in the mPFC-amygdala circuit using a primate model and clinically relevant doses of anesthesia. Materials and methods: Two non-human primates acquired aversive memories by tone-odor classical conditioning under anesthesia with different doses of ketamine, a non-competitive antagonist of NMDA and midazolam, a GABA agonist. Both agents are in wide clinical use. We simultaneously recorded single neurons in the BLA and mPFC. Analyses focused on behavioral and neural evidence suggesting maintained valence, acquisition and retention of memory. Results: Seventy-six full sessions from two non-human primates entered analysis. We recorded 172 amygdala and 189 dACC neurons respectively. We found evidence of successful aversive conditioning under both anesthetics and in all doses. Under anesthesia, we found behavioral evidence of retention in 46% of sessions matched by a complementary response of 16.2% and 18.7% of amygdala and mPFC neurons respectively. An increased and escalating amygdala and mPFC response during acquisition predicted later retention and correlated the behavioral result. The behavioral and neural representation of aversive valence was sufficient to drive learning and affected conditioning outcome. Conclusion: Our results suggest that under anesthesia, the perception of stimuli and implicit aversive memory formation may be maintained. We show patterns in the amygdala-mPFC circuit that precede and predict this phenomenon and that may serve future monitoring strategies of anesthetized patients. The use of a primate model and therapeutic doses of common anesthetics affecting both GABA and NMDA transmission improves the possible translation of our findings.

    Emotional valence and implicit memory formation under anesthesia: Neural mechanisms in the amygdala and pre-frontal cortex

    Date:
    24
    Wednesday
    October
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Nella and Leon Benoziyo Building for Brain Research
    Lecturer: Nir Samuel (PhD Thesis Defense)
    Organizer: Department of Neurobiology
    Details: Benoziyo Brain Research Building Room 113 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: Background: The aim of anaesthesia is to eliminate awareness and prevent memory ...Background: The aim of anaesthesia is to eliminate awareness and prevent memory of the various aversive stimuli of medical procedures. Yet in a portion of cases, patients can recall events that occurred during surgery resulting in risks of adverse psychological outcomes. Fear conditioning offers a robust behavioral model to study this phenomenon, while the abundant evidence implicating the amygdala-medial prefrontal cortex (mPFC) circuit in acquisition, consolidation and retrieval of these memories offers a natural hypothesis for the neural mechanisms. Objective: We aimed to study the effect of anaesthesia on stimulus valence, acquisition and memory and to identify the correlates in the mPFC-amygdala circuit using a primate model and clinically relevant doses of anesthesia. Materials and methods: Two non-human primates acquired aversive memories by tone-odor classical conditioning under anesthesia with different doses of ketamine, a non-competitive antagonist of NMDA and midazolam, a GABA agonist. Both agents are in wide clinical use. We simultaneously recorded single neurons in the BLA and mPFC. Analyses focused on behavioral and neural evidence suggesting maintained valence, acquisition and retention of memory. Results: Seventy-six full sessions from two non-human primates entered analysis. We recorded 172 amygdala and 189 dACC neurons respectively. We found evidence of successful aversive conditioning under both anesthetics and in all doses. Under anesthesia, we found behavioral evidence of retention in 46% of sessions matched by a complementary response of 16.2% and 18.7% of amygdala and mPFC neurons respectively. An increased and escalating amygdala and mPFC response during acquisition predicted later retention and correlated the behavioral result. The behavioral and neural representation of aversive valence was sufficient to drive learning and affected conditioning outcome. Conclusion: Our results suggest that under anesthesia, the perception of stimuli and implicit aversive memory formation may be maintained. We show patterns in the amygdala-mPFC circuit that precede and predict this phenomenon and that may serve future monitoring strategies of anesthetized patients. The use of a primate model and therapeutic doses of common anesthetics affecting both GABA and NMDA transmission improves the possible translation of our findings.

    Synapsins regulate alpha-synuclein function

    Date:
    23
    Tuesday
    October
    2018
    Lecture / Seminar
    Time: 12:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Daniel Gitler
    Organizer: Department of Neurobiology
    Details: Host: Dr.Ivo Spiegel ivo.spiegel@weizmann.ac.il tel: 4415 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: The normal function of alpha-synuclein, a protein involved in Parkinson's Diseas ...The normal function of alpha-synuclein, a protein involved in Parkinson's Disease and other synucleinopathies, remains elusive. Though recent studies suggest that alpha-synuclein is a physiological attenuator of synaptic vesicle recycling, mechanisms remain unclear. Our data show that synapsin – a cytosolic protein with established roles in synaptic vesicle mobilization and clustering – is required for alpha-synuclein function. Furthermore, we show that the two proteins interact in a reversible manner in the synapse and that in the absence of synapsins, the localization of alpha-synuclein to synapses is deficient. Our data suggest a model where alpha-synuclein and synapsin cooperate in clustering SVs and attenuating recycling.

    Northern exposure – The study of host-virus interactions from the lab to the Norwegian Fjords

    Date:
    23
    Tuesday
    October
    2018
    Lecture / Seminar
    Time: 11:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Daniella Schatz
    Organizer: Department of Plant and Environmental Sciences

    Targeting DNA and RNA repeats responsible for neurological disorders by small organic molecules

    Date:
    22
    Monday
    October
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Special Guest Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Kazuhiko Nakatani
    Organizer: Department of Biological Regulation

    G-INCPM - Special Seminar - Dr. Wolfgang Mann, CEO, BlueCatBio GmbH, Germany - "Blue Washer: the most cost-effective tool to improve data quality (z') for adherent cellular assays"

    Date:
    22
    Monday
    October
    2018
    Lecture / Seminar
    Time: 11:00-12:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Organizer: Life Sciences
    Abstract: Since its introduction in 2015 the BlueWasher has rapidly become the de-facto st ...Since its introduction in 2015 the BlueWasher has rapidly become the de-facto standard for media change & cell wash in adherent cellular assays. The BlueWasher uses centrifugation instead of aspiration to remove liquids from all plate formats, including 1536w, eliminating background and variability at their (assay) sources. Highly reproducible residual volumes 10x lower than conventional plate washers enable imagers to produce cleaner images, raising z' 0.1-0.3 for typical adherent cellular assays. Higher z' means to miss fewer active compounds and reduce false positives to re-screen. BlueWasher immediately improves screening economics without complex assay or automation changes, delivering unparalleled ROI and direct boost to overall drug discovery productivity. A technical introduction into centrifugation based cell wash / media changed will be followed by a number of examples discussing improvement of data quality in HTS / HCS. Other bead based applications like nucleic acids extraction or protein binding assays will be presented as well.

    G-INCPM-Special Seminar - Prof. Rony Seger, Department of Biological Regulation, Weizmann Institute - "Targeting the nuclear translocation of MAPKs as a novel anti-inflammatory and anti cancer therapy"

    Date:
    17
    Wednesday
    October
    2018
    Lecture / Seminar
    Time: 11:00-12:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Organizer: Department of Biomolecular Sciences
    Abstract: A hallmark of MAPK signaling is their nuclear translocation upon stimulation, wh ...A hallmark of MAPK signaling is their nuclear translocation upon stimulation, which is necessary for their physiological/pathological functions. We have identified two novel, distinct, regulated nuclear translocation mechanisms for ERK1/2 and JNK/p38, of which we made use of as a promising therapeutic approach. We developed a myristoylated, NTS-derived phosphomimetic peptide (EPE peptide), which blocked ERK1/2 nuclear translocation. In culture, the EPE peptide induced apoptosis of melanoma cells, inhibited the proliferation of other cancer cells but had no effect on immortalized cells. Combination of the EPE peptide and the MEK inhibitor had synergistic antitumor activity in mutated NRAS, BRAF and NF1 melanoma and Kras pancreatic cells. In xenograft models, the peptide was significantly more effective than BRAF inhibitors in preventing tumor recurrence of treatment-eradicated melanoma xenografts. We also developed p38-derived myristoylated peptide, termed PERY peptide, which inhibited the importin interaction with JNK1/2 and p38α/β and prevented their nuclear translocation. This peptide affected viability of several breast cancer-derived cell lines, and significantly reduced inflammation and intestinal damage in a mouse model of colitis. Moreover, the peptide inhibited inflammation-induced colorectal cancer in a AOM/DSS mouse model. Taken together, both the cancer and inflammatory models support the use of nuclear translocation of MAPKs as a novel drug target for signaling-related diseases.

    Expeditious Synthesis of Bacterial Glycoconjugates

    Date:
    16
    Tuesday
    October
    2018
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Prof. Suvarn S. Kulkarni
    Organizer: Department of Organic Chemistry
    Abstract: Expeditious Synthesis of Bacterial Glycoconjugates Suvarn S. Kulkarni Depart ...Expeditious Synthesis of Bacterial Glycoconjugates Suvarn S. Kulkarni Department of Chemistry, IIT Bombay, Powai, Mumbai-400076 Bacterial glycoconjugates are comprised of rare D and L deoxy amino sugars, which are not present on the human cell surface. This peculiar structural difference allows discrimination between the pathogen and the host cell and offers avenues for target-specific drug discovery and carbohydrate-based vaccine development. However, they cannot be isolated with sufficient purity in acceptable amounts, and therefore chemical synthesis is a crucial step toward the development of these products.1 We recently established short and convenient methodologies for the synthesis of orthogonally protected bacterial D and L-deoxy amino hexopyranoside and glycosamine building blocks starting from cheaply available D-mannose and L-rhamnose.2-4 The one-pot protocols rely on highly regioselective nucleophilic displacements of triflates. These procedures have been applied to the synthesis of various bacterial glycoconjugates2-8 (Figure 1) as well as metabolic oligosaccharide engineering.7 1) Emmadi, M.; Kulkarni, S. S. Nat. Prod. Rep. 2014, 31, 870-879. 2) Emmadi, M.; Kulkarni, S. S. Nature Protocols 2013, 8, 1870-1889. 3) Sanapala, S. R.; Kulkarni S. S. J. Am. Chem. Soc. 2016, 138, 4938−4947. 4) Sanapala, S. R.; Kulkarni S. S. Org. Lett. 2016, 18, 3790–3793. 5) Podilapu, A. R.; Kulkarni, S. S. Org. Lett. 2014, 16, 4336-4339. 6) Sanapala, S. R.; Kulkarni, S. S., Chem. Eur. J. 2014, 20, 3578-3583. 7) Clark, E.; I.; Emmadi, M.; Krupp, K. L.; Podilapu, A. R.; Helble, J. D.; Kulkarni, S. S.; Dube, D. H. ACS Chem Biol 2016, 11, 3365-3373. 8) Podilapu, A. R.; Kulkarni, S. S. Org. Lett. 2017, 19, 5466-5469.

    Life Science Colloquium

    Date:
    15
    Monday
    October
    2018
    Colloquium
    Time: 11:00-12:00
    Title: Senescent cells in health and disease
    Location: Dolfi and Lola Ebner Auditorium
    Lecturer: Prof. Jan van Deursen
    Organizer: Life Sciences

    Serotonin and Autism Therapeutics: Insights from Human Mutations and Mouse Models

    Date:
    14
    Sunday
    October
    2018
    Lecture / Seminar
    Time: 10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Randy Blakely
    Organizer: Department of Neurobiology
    Details: Host: Prof. Menahem Segal Menahem.segal@weizmann.ac.il tel: 2553 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: Signs of serotonergic dysfunction appeared more than 50 years ago with findings ...Signs of serotonergic dysfunction appeared more than 50 years ago with findings of hyperserotonemia in a subset of subjects with ASD, work replicated in multiple studies across the years, and accompanied by supportive data in human and animal studies. Owing to the early elaboration of serotonergic neurons in the mammalian CNS, and genetic evidence for male-specific linkage to ASD overlying the SERT gene locus, we screened multiplex ASD families for evidence of penetrant coding variants in the serotonin transporter, SERT, reporting these in 2005 and evidence that the most common of these, SERT Ala56, demonstrates alterations in the three core domains of the disorder when introduced into the mouse genome, in 2012. More recently, we have identified signaling pathways that lead to aberrant hyperactivity of SERT Ala56 in vitro and in vivo, leading to a novel therapeutic approach, involving manipulation of p38 MAPK. The talk will review the history of the work and next steps in understanding the serotonergic contribution to ASD features arising from other mutations and environmental perturbations.

    Unraveling novel protease activity mechanisms at the tumor microenvironment of pancreas cancers

    Date:
    08
    Monday
    October
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Irit Sagi
    Organizer: Department of Biological Regulation

    “From “Crowdoxidation” to Organoselenide C-E Bond Cleavage: Enlisting the help of Chalcogens in Analysis of Biological Systems Trough Novel Probe Design”

    Date:
    25
    Tuesday
    September
    2018
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Prof. David G. Churchill
    Organizer: Department of Organic Chemistry
    Abstract: Our laboratory is studying small molecule selenium-containing organic and organo ...Our laboratory is studying small molecule selenium-containing organic and organometallic systems for their potential selective fluorescence imaging properties; our goal is to eventually probing aspects of neurodegenerative disease and disease models in a more precise way based on the present state of the art. Like some transition metals, heavier chalcogens also have capacity for redox with common changes in their valence state from 2 to 4 and from 4 to 6 being possible. Also, reduced heavier chalcogenide centers such as selenium have the ability for metal chelation. The optical characteristics are sometimes profoundly changed by an additional 2+ oxidation state at e.g. a selenium atom when the Se is in an aromatic ring or as a direct aryl substituent to a fluorogenic framework. While the atom which can become chemically oxidized may be contained within an aromatic ring, or present as a substituent, there is also the possibility for C-E bond rupture; C-Se bond c! leavage was studied with selective biothiol detection in mind and therefore, the extent of Se-C rupture possible is a design parameter in these small fluorogenic molecules and its study is ongoing. Sulfur chemistry in biology is dynamic and diverse; therefore, we are hereby exploring the extent of versatility available for selenium in small synthetic molecules in the context of biology, and specifically, towards better understanding and addressing aging and neurodegenerative disease research.

    Proteomic analysis of breast cancer heterogeneity

    Date:
    20
    Thursday
    September
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Special Guest Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Tamar Geiger
    Organizer: Department of Biological Regulation
    Abstract: For more information and assistance with Accessibility issues, please contact ...For more information and assistance with Accessibility issues, please contact Rina Tzoref, Seminars Coordinator: li.tzoref@weizmann.ac.il Batya Greenman: batya.greenman@weizmann.ac.il Host Prof. Yosef Yarden 08 934 4015 yosef.yarden@weizmann.ac.il Breast cancer is a heterogeneous group of diseases, traditionally distinguished based on the expression levels of three key receptors: Estrogen receptor, progesterone receptor and Her2. However extensive mRNA expression studies, and genomic studies show higher complexity of classification and can further subdivide the tumors. In our work, we apply mass spectrometry-based proteomics analysis and challenge the existing classification. Furthermore, we analyze the internal tumor heterogeneity by dividing the tumors according to their histopathological parameters, and identify the diversity of proteomic profiles within single tumors. Altogether, the proteomic approach was able to unravel hidden layers within this complex disease.

    Diversity of transcriptional machineries that drive resistance to anti-tumor agents in head and neck cancer

    Date:
    12
    Wednesday
    September
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Speciqal Guest Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Moshe Elkabets
    Organizer: Department of Biological Regulation
    Abstract: Drug resistance is a major barrier in medical oncology. Refractoriness to anti-c ...Drug resistance is a major barrier in medical oncology. Refractoriness to anti-cancer therapies is attributed to autonomous-tumor cell survival signaling (intrinsic mechanisms) or is mediated by growth factors secreted by cells in the tumor microenvironment (extrinsic mechanisms). Here I will describe the transcriptional machineries that regulate the expression of receptor tyrosine kinases following treatments with PI3K and EGFR therapies in squamous cell carcinoma of the head and neck. Specifically, I will show that AP-1 regulates AXL expression in PI3K-resistant cells, and EHF determines HER2/3 expression following EGFR inhibition.

    Cancer persisters

    Date:
    26
    Thursday
    July
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Ravid Straussman
    Organizer: Department of Biological Regulation
    Abstract: Persister cells are considered a unique, small sub-population of cancer cells th ...Persister cells are considered a unique, small sub-population of cancer cells that maintain viability under anti-cancer treatments. Persisters do not harbor classic resistance-mediating genetic mutations, and their drug-resistance phenotype is thought to be reversible. I will describe our novel findings related to the persisters phenotype and how these findings can be exploited to rationally design novel drug combinations optimized to eliminate persisters.

    Metamaterials: Going Beyond What Nature Gives Us

    Date:
    25
    Wednesday
    July
    2018
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Amy Szuchmacher Blum
    Organizer: Department of Materials and Interfaces
    Abstract: Material properties generally arise from the chemical identities of the constitu ...Material properties generally arise from the chemical identities of the constituents. However, as our understanding of how electromagnetic waves interact with matter has grown, it has become possible to design materials whose properties depend on structure rather than composition to produce effects not seen before in nature. These newly developed materials, known as metamaterials, will be the focus of this talk. Metamaterials describe a class of materials in which material properties arise from the interaction of electromagnetic waves with the sub-wavelength sized component structures that constitute them. It has become clear that producing nano-based materials such as metamaterials requires breakthroughs in the ability to position materials with nanometer precision. This desire has led to a growing interest in bottom-up, self-assembling systems. Our approach is to use biomolecules as scaffolds because of the specificity and versatility they provide. The use of viruses as nanoscale scaffolds offers the promise of exquisite control for positioning, using a particle that can undergo further self-assembly into extended structures, and allowing the simultaneous creation of many identical complex submicron geometrical structures. Here, we present tobacco mosaic virus (TMV) coat protein as a template to produce nanostructured metamaterials. We construct plasmonically coupled nanorings on a sub-30nm size scale using a disk-shaped aggregate of TMV as a template. Computational models suggest that these rings may display metamaterial behavior at optical frequencies. Ensemble spectroscopic measurements reveal intriguing optical properties. Preliminary dark field scattering data, obtained for individual surface bound ring structures, is remarkably consistent with ensemble measurements, demonstrating that the observed optical properties arise from the ring structures. Thus, we show the utility of virus templates in generating nanostructured building blocks for advanced materials.

    G-INCPM - Special Seminar - Prof. Jürgen Reichardt, Vice-Chancellor for Research and Innovation, Yachay Tech University, Ecuador - "Quo vadis, genoma? Lessons from Galactosemia, Prostate Cancer and Atherosclerosis"

    Date:
    23
    Monday
    July
    2018
    Lecture / Seminar
    Time: 11:00-12:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Jürgen Reichardt
    Organizer: Department of Biomolecular Sciences
    Abstract: Juergen Reichardt will report on the genetic and biochemical characterization of ...Juergen Reichardt will report on the genetic and biochemical characterization of galactosemia mutations. Furthermore, he will describe the molecular epidemiology of prostate cancer, incl. the racial/ethnic variation of risk and the molecular and biochemical dissection of SNPs (single nucleotide polymorphisms), haplotypes and compound heterozygotes. These data will be related to prostate cancer prevention and the PCPT (the Prostate Cancer Prevention Trial) which enrolled 18,000 men in the US and Canada. Furthermore, Juergen will delve into the ongoing issues with SNP databases. Lastly, he will discuss future directions in the context of his career.

    EGFR/Ceramide and lung cancer development under stress

    Date:
    18
    Wednesday
    July
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Special Guest Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Tzipi Goldkorn
    Organizer: Department of Biological Regulation

    Human physiological and behavioral responses to olfactory stimuli in health and disease

    Date:
    17
    Tuesday
    July
    2018
    Lecture / Seminar
    Time: 12:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Liron Rozenkrantz (PhD Thesis Defense)
    Organizer: Department of Neurobiology
    Details: Dept of Neurobiology-Students & Postdocs Seminar For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: In my PhD I led three projects probing human behavioral and physiological respon ...In my PhD I led three projects probing human behavioral and physiological responses to olfactory stimuli in health and disease. In these projects I used every-day olfactory occurrences in order to infer on biological underpinnings of human behavior. In my main project I tested olfactory processing in autism, using the sniff response, a ten-minute non-verbal measure of respiratory response to odors. I found this objective measure to be profoundly altered in children with autism, and furthermore, to be highly correlated with autism severity. Using computational methods, I demonstrated 81% correct ASD classification based on differences in olfactory processing alone. These results provide proof-of-concept for a potential biomarker for autism (Rozenkrantz et al, Curr Bio, 2015). In a second and soon-to-be-submitted project, I investigated olfactory social communication in recurrent pregnancy loss (RPL), resting on a phenomenon in rodents in which females miscarry following exposure to bodily odors of non-stud males. I found that women with RPL display heightened social olfactory abilities, which were significantly correlated with number of miscarriages. Additionally, women with RPL showed significantly altered hormonal, physiological and neural responses to body odors of unfamiliar men. This project provides novel evidence for altered olfactory processing in human recurrent miscarriages. The third project is also my first foothold in placebo effect research, which I will pursue in my postdoc. Taking advantage of the non-invasive nature of olfactory stimuli, I used an odor as the placebo carrier, and tested two groups of subjects for different creativity tests. Both groups smelled the odor, but only the placebo group was told that it increases creativity (placebo manipulation). I found that following this simple manipulation, the placebo group displayed significantly enhanced creativity (Rozenkrantz et al., PLoS one, 2017). Taken together, these projects convey my deep interest in the interplay between human behavior and physiology.

    Single-molecule Visualization of Long-range Epigenetic Regulation

    Date:
    12
    Thursday
    July
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Yuval Ebenstein
    Organizer: Department of Biological Regulation
    Abstract: Epigenetic regulation by DNA methylation is well established in the context of t ...Epigenetic regulation by DNA methylation is well established in the context of the classical Promoter:Coding box. Recent genome-wide association studies (GWAS) indicate that the methylation state of distant enhancers play a critical role in gene expression. In cancer, such distant epigenetic aberrations can have significant effects on carcinogenesis. In order to uncover these long-range interactions on the single-cell level, I present an epigenome-mapping technology based on fluorescent tagging of epigenetic marks on long individual DNA molecules. Information is read as a fluorescent genetic/epigenetic barcode that provides genome-scale profiles with extremely long reads. I discuss our progress towards simultaneous recording of methylation and transcription information from the same molecules with the aim of discovering and characterizing epigenetic gene-regulation at a distance.

    MODELING PROTEIN CONFORMATIONAL CHANGES WITH CROSS-LINKS AND SAXS PROFILES

    Date:
    03
    Tuesday
    July
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Dr. Dina Schneidman
    Organizer: Department of Structural Biology
    Abstract: Proteins generally populate multiple structural states in solution. Transitions ...Proteins generally populate multiple structural states in solution. Transitions between these states are important for function, such as allosteric signaling and enzyme catalysis. Structures solved by X-ray crystallography provide valuable, but static, atomic resolution structural information. In contrast, cross-linking mass spectrometry (XLMS) and small angle X-ray scattering (SAXS) datasets contain information about conformational and compositional states of the system. The challenge lies in the data interpretation since the cross-links in the data often comes from multiple structural states. We have developed a novel computational method that simultaneously uncovers the set of structural states that are consistent with a given dataset (XLMS or SAXS). The input is a single atomic structure, a list of flexible residues, and an experimental dataset. The method finds multi-state models (models that specify two or more co-existing structural states) that are consistent with the data. The method was applied on multiple SAXS and XLMS datasets, including large multi-domain proteins and proteins with long disordered fragments. The applicability of the method extends to other datasets, such as 2D class averages from Electron Microscopy, and residual dipolar couplings.

    Microbial Interactions and Climate Reconstructions

    Date:
    01
    Sunday
    July
    2018
    Lecture / Seminar
    Time: 11:00
    Location: Sussman Family Building for Environmental Sciences
    Lecturer: Einat Segev
    Organizer: Department of Earth and Planetary Sciences
    Abstract: Micro-algae greatly influence present and past oceans. Recently we have come to ...Micro-algae greatly influence present and past oceans. Recently we have come to realize that bacteria interact with micro-algae in various ways, ranging from pathogenicity to mutualism. My research investigates physical and chemical interactions between micro-algae and bacteria across multiple scales; from the chemical crosstalk to the influence these interactions have on the marine environment. In my talk I will introduce Emiliania huxleyi, the most prevalent micro-alga in modern oceans. I will discuss the role of bacteria as hidden farmers that control the life cycle of algae, determining how fast algae will grow and how fast they will die. I will link laboratory findings to work conducted at sea and demonstrate the importance of these findings in the study of proxies for climate reconstructions.

    Physicists working on Cancer

    Date:
    01
    Sunday
    July
    2018
    -
    12
    Thursday
    July
    2018
    Conference
    Time: 08:00
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Organizer: Faculty of Physics

    PHYSICISTS WORKING ON CANCER

    Date:
    01
    Sunday
    July
    2018
    -
    12
    Thursday
    July
    2018
    Conference
    Time: 08:00
    Location: Nella and Leon Benoziyo Physics Library
    Organizer: Faculty of Physics

    Structural view of the disordered multi-tasker WIP and its interaction network in human T cells

    Date:
    26
    Tuesday
    June
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Prof. Jordan Chill
    Organizer: Department of Structural Biology
    Abstract: WASP-Interacting Protein (WIP) is a multifunctional key participant in mediating ...WASP-Interacting Protein (WIP) is a multifunctional key participant in mediating actin-related cytoskeletal changes in human T cells. WIP is also an intrinsically disordered protein (IDP), lacking any significant secondary or tertiary structure across its 503 residues, and thus defies the ordinarily reliable structure-function paradigm. Our research focuses on how interactions between this ‘hub’ multi-tasker and its various structured binding partners delicately control T cell destiny, in particular the role played by disorder-to-order transitions. Three such critical protein-protein contacts involve the WIP N-terminal domain (with actin), a proline-rich central segment (with cortactin) and the C-terminal domain (with Wiskott-Aldrich syndrome protein, WASP). The first two are of intermediate binding energy (KD ~ 50-3000 nM) and transiently modulate WIP interactions with the actin polymerization machinery. In contrast, the latter forms a tight complex with WASP and inhibits both its activity and eventual degradation in a phosphorylation-dependent manner, explaining why the hereditary Wiskott-Aldrich syndrome immunodeficiency results from WASP mutants unable to bind WIP. As an IDP, WIP ‘structure’ is essentially an ensemble of multiple conformations contributing to function, and this complexity gives solution NMR – armed with new IDP-optimized methodologies – unrivaled insight into how IDPs exert their biological influence. We established that transient structure in free WIPN and WIPC echoes their bound conformations, uncovering novel binding epitopes in the process. We also observed subtle ensemble shifts induced by environmental factors, such as temperature, denaturant or crowding agents, revealing the biophysics governing WIP behavior in the cellular environment. We further investigated the largest conformational change, experienced by WIPC upon binding to WASP, by determining the contribution of various WIP epitopes to complex affinity, and eventually the structure of the WIP-WASP complex. Finally, we offer an unexpected structural explanation for phosphorylation-induced dissociation of this complex that may explain how this phospho-switch controls WASP degradation. Taken together our results provide a comprehensive map of WIP structure and dynamics and how these affect its interaction with T cell binding partners, and highlight the great impact of high-resolution NMR studies upon the field of biologically active unstructured proteins.

    Neural networks mapping actions to their sensory consequences

    Date:
    26
    Tuesday
    June
    2018
    Lecture / Seminar
    Time: 12:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Roy Mukamel
    Organizer: Department of Neurobiology
    Details: Host: Dr.Ivo Spiegel ivo.spiegel@weizmann.ac.il tel: 4415 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: A specific motor action can lead to different sensory consequences, and a partic ...A specific motor action can lead to different sensory consequences, and a particular sensory consequence can be achieved by different motor actions. This non-unique mapping between actions and sensory consequences is context dependent and requires learning in order to optimize behavior. During my talk, I will describe behavioral and neuroimaging studies in humans, in which we examined how actions modulate perception and how perception can lead to motor skill learning even in the absence of voluntary movement. Manipulating the link between actions and their sensory consequences by using virtual reality, we explore various training techniques to facilitate learning in healthy subjects and rehabilitation in patients with hemiparesis due to neurological origin.

    Molecular Genetics Departmental Seminars 2017-2018

    Date:
    24
    Sunday
    June
    2018
    Lecture / Seminar
    Time: 13:00
    Title: “Modeling Autism: Maternal Immune Activation Alters the Development of the Embryonic Brain”
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Lihi Ben-Reuven
    Organizer: Department of Molecular Genetics

    FROM CANCER GENOMICS TO IMMUNOTHERAPY

    Date:
    19
    Tuesday
    June
    2018
    Conference
    Time: 08:00-14:00
    Location: Dolfi and Lola Ebner Auditorium

    A ubiquitous human carcinogen guiding the early diagnosis of cancer

    Date:
    14
    Thursday
    June
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Special Guest Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Arthur Grollman
    Organizer: Department of Biological Regulation
    Abstract: Aristolochic acid (AA) is now recognized as a causative agent of several types o ...Aristolochic acid (AA) is now recognized as a causative agent of several types of human cancer. Moreover, as a component of Aristolochia, a widely used medicinal herb, it is now clear that people have been exposed to toxic levels of AA for hundreds of years, worldwide. Today, tens of millions of people are at risk of developing AA-induced cancers of the upper urothelium, kidney, liver and biliary tract. In addition, aristolochic acid was proven to be the environmental agent responsible for Balkan endemic nephropathy and its associated urothelial cancer. And, exposure to AA accounts for the high prevalence of upper urothelial cancer in Taiwan, the highest in the world. It has also been shown that AA-induced cancers are accompanied by a unique mutational signature, which can be used to identify AA-induced cancers in individuals who would otherwise be undiagnosed until the later stages of disease. Such analyses have established the foundation for a noninvasive approach for detection of urothelial cancer in patients at risk.

    Osteoclasts and Bone Resorption in Health and Disease

    Date:
    10
    Sunday
    June
    2018
    -
    11
    Monday
    June
    2018
    Conference
    Time: 08:00
    Location: David Lopatie Conference Centre

    The best cancer therapy is prevention and early detection: the decade-long perspectives of our Integrated Cancer Prevention Center

    Date:
    07
    Thursday
    June
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Nadir Arber
    Organizer: Department of Biological Regulation

    Prostate Cancer

    Date:
    07
    Thursday
    June
    2018
    Lecture / Seminar
    Time: 11:00-13:00
    Title: Clinical Oncology Course
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Nicola Mabjeesh
    Organizer: Department of Biological Regulation

    15th Annual Meeting of The Medicinal Chemistry Section of the Israel Chemical Society (MCS-ICS)

    Date:
    06
    Wednesday
    June
    2018
    Conference
    Time: 08:30-17:30
    Location: David Lopatie Conference Centre
    Organizer: The Dimitris N. Chorafas Institute for Scientific Exchange,G-INCPM

    MICC SPECIAL GUEST SEMINAR

    Date:
    05
    Tuesday
    June
    2018
    Lecture / Seminar
    Time: 11:00
    Title: “Back to the Future: Lessons about cancer from development”
    Location: Wolfson Building for Biological Research
    Lecturer: Professor Geoffrey M. Wahl, Ph.D
    Organizer: Department of Molecular Cell Biology

    Lung cancer and HER family proteins

    Date:
    31
    Thursday
    May
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Hovav Nechushtan
    Organizer: Department of Biological Regulation

    Brain Cancer

    Date:
    31
    Thursday
    May
    2018
    Lecture / Seminar
    Time: 11:00-13:00
    Title: Clinical Oncology Course
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Uri Tabori
    Organizer: Department of Biological Regulation

    Nano safety and Education

    Date:
    30
    Wednesday
    May
    2018
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Martin Himly
    Organizer: Department of Materials and Interfaces
    Abstract: Nanotechnology has reached every-day life. A high number of all-day products e ... Nanotechnology has reached every-day life. A high number of all-day products either contain nanomaterials (NMs) or have been processed by nanotechnological work flows. New interactions with other all-day products, i.e. an every-growing number of modern lifestyle products (MLPs), become more and more likely. Moreover, the new generation has a high degree of creativity in using MLPs in different ways potentially resulting in not foreseen interactions of NMs with MLPs during the marketing process. Therefore, an interdisciplinary research project termed Nan-O-Style has been established investigating interactions between NMs in consumer products with substances from daily life with a special focus on MLPs used by adolescents. Furthermore, Nan-O-Style aims at the compilation of an education initiative about nanotechnology including teaching resources and international peer-teaching. In order to achieve a high variety of perspectives, students from different types of Austrian higher schools (technical/scientific vs. economic vs. artistic) work in close contact with scientists from academia. Due to the within Nan-O-Style acquired competences and the established network between academic scientists, students and educational institutions, the students develop new models for interdisciplinary teaching in mathematical/scientific/technical (MINT) subjects and apply them as best practice examples. We particularly focus on schools with an economic or fashion background which typically have a higher share of girls. A number of pre-scientific projects in nano-technological, nano-biological or nano-educational topics are carried out. This approach towards interdisciplinary MINT education thus strengthens the profile formation of the Paris Lodron University of Salzburg and further extends to the education of teachers. Previously, the educational EU framework projects www.NanoTOES.eu and www.NanoEIS.eu had been coordinated by Prof. Duschl and his group. Nan-O-Style is based on this background and therefore internationally connected to educational partners in Israel (ORT Moshinsky R&D Center, Tel Aviv, http://en.ort.org.il/), Spain (Nanoeduca, Barcelona, http://nanoeduca.cat/es/inicio/), and Germany (cc-NanoBioNet e.V, Saarbrücken, http://www.nanobionet.de/). The Duschl group furthermore conducts nanosafety research involving advanced in vitro models of the human lung barrier, including air-liquid interface cultures (1), addressing potential modulations of the immune response towards NMs (2, 3). As allergens may be inhaled simultaneously to nanoparticles they can become part of the protein corona. The group investigates whether this poses a risk for people with an existing allergic condition (4).

    Enzyme rates in the omics era

    Date:
    29
    Tuesday
    May
    2018
    Lecture / Seminar
    Time: 11:30
    Title: From global characterization to a pivotal case study
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dan Davidi
    Organizer: Department of Plant and Environmental Sciences
    Abstract: Enzymes determine the rate of most biological processes. Decades of biochemistry ...Enzymes determine the rate of most biological processes. Decades of biochemistry have demonstrated how enzymes vary by orders of magnitude in their kinetic properties. Why are some enzymes faster than others and how are enzyme capacities related to physiological demands? I will talk about the interplay between enzyme kinetics and different evolutionary driving forces in an attempt to unravel which factors constrain and sculpt enzymatic rates. I will then move to examine the relevance of in-vitro kinetics to living systems, asking whether the rates of enzymes are similar between test-tubes and cells, and if not, why this is the case. Lastly, I will focus on one particular enzyme with lousy kinetics. This enzyme is called Rubisco - the key carboxylating enzyme on the planet, and therefore the gateway into the organic world. Instead of trying to improve Rubisco by directed evolution approaches, which have largely failed so far, I will describe our ongoing journey to find the best Rubisco Nature has to offer...

    Defining the microglia contributions to lysosomal storage disorders

    Date:
    29
    Tuesday
    May
    2018
    Lecture / Seminar
    Time: 10:30-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Soo-Min Cho
    Organizer: Department of Biomolecular Sciences
    Abstract: Lysosomal storage disorders (LSD), such as Gaucher disease (GD) and Niemann–Pi ...Lysosomal storage disorders (LSD), such as Gaucher disease (GD) and Niemann–Pick type C (NPC) disease, display neuronal degeneration accompanied by neuroinflammation. In the brain, innate immunity is maintained by microglia, the major myeloid cell population in the CNS. FACS analysis of end stage LSD models showed minor monocyte infiltration indicating that CNS-resident microglia are the major myeloid player in these pathologies. I will further discuss the functional contribution of microglia to LSD pathophysiology based on RNAseq analysis of microglia from various LSD animal models.

    How Malaria Parasite Tricks the Immune System

    Date:
    29
    Tuesday
    May
    2018
    Lecture / Seminar
    Time: 10:00-10:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Yifat Ofir-Birin
    Organizer: Department of Biomolecular Sciences
    Abstract: Our ability to cure infectious diseases is greatly limited by a lack of understa ...Our ability to cure infectious diseases is greatly limited by a lack of understanding of the way many pathogens evade the human innate immune system. This is indeed the case when it comes to the parasite Plasmodium falciparum (P. falciparum), the leading infectious agent of Malaria, one of the most devastating infectious diseases in humans. We show that while growing within human red blood cells, the parasites secrete extracellular vesicles containing genomic DNA, RNA and proteins. These vesicles are taken up by human monocytes, the DNA species are then released within the host cytosol leading to cytosolic STING-dependent DNA sensing. Additionally, we provide the evidence that internalization of late stage (trophozoite) P. falciparum-derived vesicles by monocytes prompts the activation of a known master regulator transcription factor, NF-kB. The activated NF-kB is then translocated to the nucleus to induce transcription of a target gene. Our finding opens a new line of investigation concerning the function of the vesicle DNA and RNA cargo components. This newly discovered crosstalk mechanism strongly supports the existence of a 'manipulation strategy' of the host immune environment by the deadly pathogen, P. falciparum parasite.

    Pancreatic Cancer Biology & Medicine

    Date:
    29
    Tuesday
    May
    2018
    Lecture / Seminar
    Time: 09:30
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. David Tuveson
    Organizer: Department of Molecular Cell Biology

    From Photosynthesis to Cancer Therapy

    Date:
    27
    Sunday
    May
    2018
    -
    28
    Monday
    May
    2018
    Conference
    Time: 08:00
    Location: David Lopatie Conference Centre

    Targeting Pancreas Cancer

    Date:
    24
    Thursday
    May
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. David Kelsen
    Organizer: Department of Biological Regulation

    Breast Cancer

    Date:
    24
    Thursday
    May
    2018
    Lecture / Seminar
    Time: 11:00-13:00
    Title: Clinical Oncology Course
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Tamar Peretz-Yablonski
    Organizer: Department of Biological Regulation

    Computational tools for

    Date:
    17
    Thursday
    May
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Club Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Ron Shamir
    Organizer: Department of Biological Regulation

    Bacterial effects on Algal life, death, and geology

    Date:
    15
    Tuesday
    May
    2018
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Einat Segev
    Organizer: Department of Biomolecular Sciences
    Abstract: Micro-algae greatly influence our oceans and have shaped the history of our plan ...Micro-algae greatly influence our oceans and have shaped the history of our planet. Recently we have come to realize that bacteria interact with micro-algae in various ways, ranging from pathogenicity to mutualism. My research investigates physical and chemical interactions between micro-algae and bacteria across multiple scales; from the chemical crosstalk to the influence these interactions have on the marine environment. In my talk I will introduce Emiliania huxleyi, the most prevalent micro-alga in modern oceans. I will discuss the role of bacteria as hidden farmers that control the life cycle of algae, determining how fast algae will grow and how fast they will die. I will link laboratory findings to work conducted at sea and demonstrate the importance of these findings in climate reconstructions.

    Molecular Genetics Departmental Seminars 2017-2018

    Date:
    13
    Sunday
    May
    2018
    Lecture / Seminar
    Time: 13:00
    Title: "m6A modification sculpts innate immune response to infection”
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Roni Winkler
    Organizer: Department of Molecular Genetics

    Senescent cells and the dynamics of ageing

    Date:
    10
    Thursday
    May
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Uri Alon
    Organizer: Department of Biological Regulation

    Deciphering the cellular copper trafficking mechanism in order to develop a new generation of antibiotics and biomarkers

    Date:
    10
    Thursday
    May
    2018
    Lecture / Seminar
    Time: 09:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Sharon Ruthstein
    Organizer: Department of Materials and Interfaces
    Abstract: In the last couple of years, my lab has been exploring the cellular copper cyc ... In the last couple of years, my lab has been exploring the cellular copper cycle in eukaryotic and prokaryotic systems using Electron Paramagnetic Resonance (EPR) spectroscopy. While most of the proteins involved in the copper cycle are believed to be known, as well as some of the crystal structures, there is still lack of information on the kinetic and the transfer mechanism of the copper in the cellular environment. Since dysfunction of the copper regulation system can lead to neurological diseases and to the cell death, it is essential to understand every little detail in the copper ycle to be able to control it according to specific needs EPR has become a powerful tool for studying complex dynamic biological systems since it is not limited to the protein size and does not require crystallization. Hence, the biological system can be studied in solution, lipids, and even the cellular environment. In our group, we are applying various EPR measurements together with computations, biochemistry experiments, CD and NMR to identify the copper binding sites, as well as to understand how one protein in the cycle coordinated to another protein to transfer the metal ion. We target the conformational changes that occur in each protein, and we aim to gain also kinetic data on the transfer mechanism. In this talk, I will present our results on the copper transfer mechanism in the human and E.coli cells. I will also demonstrate how basic understanding of the function of these systems can assist us in designing new class of antibiotics and biomarkers for hypoxic systems.

    Atlases of structure-function relationships in small motifs: the limits of modularity

    Date:
    08
    Tuesday
    May
    2018
    Lecture / Seminar
    Time: 14:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Dr. James Sharpe
    Organizer: Azrieli Institute for Systems Biology
    Abstract: Abstract: I will discuss our work on visualizing “topology atlases” which a ...Abstract: I will discuss our work on visualizing “topology atlases” which act as a map of possible circuit designs for small 3-node regulatory motifs. These can help in understanding the relationship between a circuit's structure and its function, but how is this relationship affected if the circuit must perform multiple distinct functions within the same organism? In particular, to what extent do multi‐functional circuits contain modules which reflect the different functions? We computationally surveyed a range of bi‐functional circuits which show no simple structural modularity: They can switch between two qualitatively distinct functions, while both functions depend on all genes of the circuit. Our analysis revealed two distinct classes: hybrid circuits which overlay two simpler mono‐functional sub‐circuits within their circuitry, and emergent circuits, which do not. In this second class, the bi‐functionality emerges from more complex designs which are not fully decomposable into distinct modules and are consequently less intuitive to predict or understand. These non‐intuitive emergent circuits are just as robust as their hybrid counterparts, and we therefore suggest that the common bias toward studying modular systems may hinder our understanding of real biological circuits. Relevant papers: 1. A spectrum of modularity in multi-functional gene circuits. Jiménez A, Cotterell J, Munteanu A, Sharpe J. (2017) Mol Syst Biol 13(4):925. doi: 10.15252/msb.20167347 http://msb.embopress.org/content/13/4/925 2. An atlas of gene regulatory networks reveals multiple three-gene mechanisms for interpreting morphogen gradients. Cotterell J, Sharpe J. (2010) Mol Syst Biol 6:425. doi: 10.1038/msb.2010.74 http://msb.embopress.org/content/6/1/425 Bio: James Sharpe was originally captivated by computer programming, but upon learning about the digital nature of the genetic code, chose to study Biology for his undergraduate degree at Oxford University (1988-1991). He then did his PhD on the genetic control of embryo development at NIMR, London (1992-1997) and in parallel started writing computer simulations of multicellular development. During his post-doc in Edinburgh, he began modelling the dynamics of limb development, and also invented a new optical imaging technology called Optical Projection Tomography (OPT), which is dedicated to imaging specimens too large for microscopy - tissues and organs. In 2006 he moved to Barcelona, becoming a senior group leader at the Centre for Genomic Regulation, and focusing on a systems biology approach to modelling limb development – combining experimentation with computer modelling. In this way the group demonstrated that the signalling proteins which pattern the fingers during embryogenesis, act as a Turing reaction-diffusion system. In 2011 he became the coordinator of the Systems Biology Program, and in 2017 was recruited to EMBL as Head of the new Barcelona outstation on Tissue Biology and Disease Modelling.

    When is a Drug Price Unjust?

    Date:
    01
    Tuesday
    May
    2018
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Ezekiel J. Emanuel
    Organizer: Life Sciences

    Modeling the initiation, progression and treatment of human melanoma in the mouse

    Date:
    30
    Monday
    April
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Special Guest Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Glenn Merlino
    Organizer: Department of Biological Regulation

    Pancreas cancer, inflammation, and immunity: of mice and men

    Date:
    29
    Sunday
    April
    2018
    Lecture / Seminar
    Time: 10:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Dr. Francisco X Real & Dr. Núria Malats
    Organizer: Department of Molecular Cell Biology

    PAPD7: a non-canonical poly(A) RNA polymerase that regulates replication across DNA damage.

    Date:
    24
    Tuesday
    April
    2018
    Lecture / Seminar
    Time: 10:30-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Umakanta Swain
    Organizer: Department of Biomolecular Sciences
    Abstract: Translesion DNA synthesis (TLS) overcomes arrest of replication forks at DNA les ...Translesion DNA synthesis (TLS) overcomes arrest of replication forks at DNA lesions, by allowing synthesis across the damaged sites by specialized low-fidelity TLS DNA polymerases. This prevents double-strand breaks and genomic instability at the cost of increased point mutations. An siRNA screen performed in our lab in search for novel regulatory mammalian TLS genes, identified 17 novel TLS genes, one of which was PAPD7 (Poly (A) polymerase D7), a putative non-canonical poly(A) RNA polymerase. The biological role of PAPD7 is unknown yet. We over-expressed and partially purified recombinant human PAPD7 and showed that it is indeed an adenylyltransferase. Measuring TLS across site-specific benzo[a]pyrene–G (BP-G), a major cigarette smoke DNA-adduct, we show that the down-regulation of PAPD7 decreased TLS across BP-G, and also decreased its mutagenicity. Further analysis showed that at least part of PAPD7 regulation of TLS is via its effect on monoubiquitination of PCNA (the DNA sliding clamp), a key step in TLS. RNA-seq analysis followed enrichment analysis showed that PAPD7 is involved in several biological functions including RNA metabolism, development, inflammation, signalling, cell cycle and DNA replication. Current studies are aimed at better understanding the molecular mechanism of TLS regulation by PAPD7.

    Computational design of new and improved enzymes

    Date:
    24
    Tuesday
    April
    2018
    Lecture / Seminar
    Time: 10:00-10:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Olga Khersonsky
    Organizer: Department of Biomolecular Sciences
    Abstract: Enzymes are potent biocatalysts that are widely used in biotechnology, but their ...Enzymes are potent biocatalysts that are widely used in biotechnology, but their function often has to be altered or optimized. Enzyme evolution and engineering are constrained by epistatic relationships among the positions that make up an active site. A further constraint is due to stability-function tradeoffs, whereby accumulated mutations reduce protein stability and functional expression. To address these problems, we have developed several new methods that use bioinformatics and Rosetta atomistic simulations to stabilize enzymes, improve their activity and make new enzymes by modular backbone assembly.

    "Genomic approaches to studying cancer aneuploidy"

    Date:
    23
    Monday
    April
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Uri Ben-David
    Organizer: Department of Biological Regulation
    Details: Abstract: Cancer aneuploidy is a biological enigma and a missed opportunity for cancer treatment. The association between cancer and aneuploidy has been well known for decades, but there has been rather limited progress in understanding how aneuploidy contributes to cancer initiation and progression. In this talk, I will discuss my postdoctoral work that applied genomic approaches to study the relevance of aneuploidy to cancer pathogenesis. In my first study, I analyzed genetically engineered mouse models of cancer and revealed a driver-specific pattern of aneuploidy. This work narrowed down the region of interest in one of the most recurrent chromosomal changes in human breast cancer (loss of chromosome 1p), and identified a gene (Sfn) that cooperates with Erbb2 during breast cancer tumorigenesis. In a second study, I analyzed patient-derived xenografts (PDXs) and revealed distinct tumor evolution trajectories in patients and in mice. This work also identified significant associations between recurrent aneuploidies and drug response. In a third study, I analyzed cancer cell lines and revealed that the genomic instability of these models results in altered transcriptional programs and disparate drug response. This work also yielded a novel isogenic system to study cancer aneuploidy in vitro. Together, these three works shed new light on the faithfulness and stability of the most commonly used cancer models, and lay a foundation for their proper use in functional studies of cancer aneuploidy.

    "Quantitative chemical imaging in vivo"

    Date:
    23
    Monday
    April
    2018
    Colloquium
    Time: 11:00-12:15
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Yamuna Krishnan
    Organizer: Faculty of Chemistry
    Abstract: Department of Chemistry & Grossman Institute of Neuroscience and Quantitative Bi ...Department of Chemistry & Grossman Institute of Neuroscience and Quantitative Biology The University of Chicago DNA can be self-assembled into molecularly precise, well-defined, synthetic assemblies on the nanoscale, commonly referred to as designer DNA nanodevices. My lab creates synthetic, chemically responsive, DNA-based fluorescent probes. (1) In 2009 my lab discovered that these designer nanodevices could function as fluorescent reporters to quantitatively image ions in real time in living systems. (2,3) Until this innovation, it was not at all obvious whether such DNA nanodevices could function inside a living cell without being interfered with, or interfering with, the cells own networks of DNA control (4). In this talk I will discuss unpublished work on how we have expanded this technology from ion imaging (5,6) to now quantitatively imaging reactive species as well as enzymatic cleavage with sub-cellular spatial resolution in vivo. References: 1. Chakraborty, K., et al., Nucleic acid based nanodevices in biological imaging. Ann. Rev. Biochem., 2016 85, 349-373. 2. Modi, S., et al. A DNA nanomachine that maps spatial and temporal pH changes in living cells. Nature Nanotechnology, 2009, 4, 325-330. 3. Modi, S., et al. Two DNA nanomachines map pH of intersecting endocytic pathways. Nature Nanotechnology, 2013, 8, 459-467. 4. Surana, S., et al. Designing DNA nanodevices for compatibility with the immune system of higher organisms. Nature Nanotechnology, 2015, 10, 741-747. 5. Saha, S., et al. A pH-insensitive DNA nanodevice quantifies chloride in organelles of living cells. Nature Nanotechnology, 2015, 10, 645-651. 6. Chakraborty, K., et al., High lumenal chloride in the lysosome is critical for lysosome function. eLife, 2017, 6, e28862. 7. Dan, K. et al., DNA nanodevices map enzymatic activity in vivo. 2018 (in revision). 8. Thekkan, S. et al A DNA-based fluorescent reporter maps HOCl dynamics in the maturing phagosome. 2018 (submitted)

    Molecular Genetics Departmental Seminars 2017-2018

    Date:
    22
    Sunday
    April
    2018
    Lecture / Seminar
    Time: 13:00
    Title: Targeting Biomineralization to Combat Antibiotic Resistant Biofilm Infections
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Alona keren-Paz
    Organizer: Department of Molecular Genetics

    G-INCPM- Special Seminar - Prof. Yuval Dor, Dept. of Developmental Biology & Cancer Research, The Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem - "Non Invasive Detection of Tissue-Specific Cell Death"

    Date:
    17
    Tuesday
    April
    2018
    Lecture / Seminar
    Time: 11:00-12:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. yuval Dor
    Organizer: Department of Biomolecular Sciences
    Abstract: Cell-free circulating DNA (cfDNA), released from dying cells, is emerging as a d ...Cell-free circulating DNA (cfDNA), released from dying cells, is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. We developed a method of detecting tissue-specific cell death in humans, based on tissue-specific methylation patterns of DNA circulating in plasma. We interrogated tissue-specific methylome datasets to identify cell type-specific DNA methylation signatures, and established a method to detect these in mixed DNA samples and in cfDNA isolated from plasma. Using this new type of biomarker it is possible to detect the presence of cfDNA fragments derived from multiple tissues in healthy individuals and in pathologies including cancer, myocardial infarction, sepsis, neurodegeneration and more. In the long run we envision this approach opening a minimally-invasive window for monitoring and diagnosis of a broad spectrum of human pathologies, as well as better understanding of normal tissue dynamics.

    Identifying and targeting

    Date:
    12
    Thursday
    April
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Cancer Research Club Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Eyal Gottlieb
    Organizer: Department of Biological Regulation

    Special Guest Seminar

    Date:
    11
    Wednesday
    April
    2018
    Lecture / Seminar
    Time: 11:00-12:00
    Title: “Apoptosis control by the unfolded protein response”
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Dr. Avi Ashkenazi
    Organizer: Department of Molecular Genetics
    Abstract: Precise protein folding by the endoplasmic reticulum (ER) supports homeostasis, ...Precise protein folding by the endoplasmic reticulum (ER) supports homeostasis, while cumulative protein misfolding causes ER stress and promotes disease. The kinases PERK and IRE1 help orchestrate the unfolded protein response (UPR) to alleviate ER stress; however, if stress persists, the UPR activates apoptosis to eliminate the damaged cell. We have previously shown that PERK drives cell death via transcriptional up-regulation of the pro-apoptotic death receptor DR5; we further showed that IRE1—which harbors both kinase and RNase modules—blocks apoptosis through regulated IRE1-dependent mRNA decay (RIDD) of DR5 (Lu et al, Science 2014). Recently, we turned to investigate the paradoxical observation that under irresolvable ER stress PERK activity persists, while IRE1 function attenuates. We discovered that PERK governs the attenuation of IRE1, through a phosphatase called RNA polymerase II-associated protein 2 (RPAP2). RPAP2 reverses IRE1 phosphorylation, inhibiting IRE1 RNase activation. This disrupts IRE1-dependent generation of the cytoprotective transcription factor XBP1s and dampens ER-associated degradation of misfolded proteins. Furthermore, it inhibits RIDD, thereby licensing DR5-mediated caspase activation and apoptotic cell death. Thus, under excessive ER stress, PERK attenuates IRE1 via RPAP2 to abort failed adaptation and trigger an apoptotic cell fate.

    Special Guest Seminar

    Date:
    11
    Wednesday
    April
    2018
    Lecture / Seminar
    Time: 11:00
    Title: Apoptosis control by the unfolded protein response
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Avi Ashkenazi, PhD
    Organizer: Department of Molecular Genetics
    Abstract: Precise protein folding by the endoplasmic reticulum (ER) supports homeostasis, ...Precise protein folding by the endoplasmic reticulum (ER) supports homeostasis, while cumulative protein misfolding causes ER stress and promotes disease. The kinases PERK and IRE1 help orchestrate the unfolded protein response (UPR) to alleviate ER stress; however, if stress persists, the UPR activates apoptosis to eliminate the damaged cell. We have previously shown that PERK drives cell death via transcriptional up-regulation of the pro-apoptotic death receptor DR5; we further showed that IRE1—which harbors both kinase and RNase modules—blocks apoptosis through regulated IRE1-dependent mRNA decay (RIDD) of DR5 (Lu et al, Science 2014). Recently, we turned to investigate the paradoxical observation that under irresolvable ER stress PERK activity persists, while IRE1 function attenuates. We discovered that PERK governs the attenuation of IRE1, through a phosphatase called RNA polymerase II-associated protein 2 (RPAP2). RPAP2 reverses IRE1 phosphorylation, inhibiting IRE1 RNase activation. This disrupts IRE1-dependent generation of the cytoprotective transcription factor XBP1s and dampens ER-associated degradation of misfolded proteins. Furthermore, it inhibits RIDD, thereby licensing DR5-mediated caspase activation and apoptotic cell death. Thus, under excessive ER stress, PERK attenuates IRE1 via RPAP2 to abort failed adaptation and trigger an apoptotic cell fate.

    Cell Penetration and Membrane Fusion: Two Sides of the Same Coin

    Date:
    10
    Tuesday
    April
    2018
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Pavel Jungwirth
    Organizer: Department of Biomolecular Sciences
    Abstract: Cell penetrating peptides have a unique potential for targeted drug delivery, th ...Cell penetrating peptides have a unique potential for targeted drug delivery, therefore, mechanistic understanding of their membrane action has been sought since their discovery over 20 years ago. While ATP-driven endocytosis is known to play a major role in their internalization, there has been also ample evidence for the importance of passive translocation for which the direct mechanism, where the peptide is thought to directly pass through the membrane via a temporary pore, has been widely advocated. In this talk, I will question this view and demonstrate that arginine-rich cell penetrating peptides can instead enter vesicles and cells by inducing multilamellarity and fusion, analogously to the action of calcium ions. The molecular picture of this penetration mode, which differs qualitatively from the previously proposed direct mechanism, is provided by molecular dynamics simulations. In addition, the kinetics of vesicle agglomeration and fusion by nonaarginine, nonalysine, and calcium ions are documented in real time by fluorescence techniques and the induction of multilamellar phases in vesicles and cells is revealed both via electron microscopy and fluorescence spectroscopy. We thus show that the newly identified passive cell penetration mechanism is analoguous to vesicle fusion induced by calcium ions, demonstrating that the two processes are of a common mechanistic origin.

    Islet 3D chromatin architecture provides insights into personalized medicine for type 2 diabetes

    Date:
    08
    Sunday
    April
    2018
    Lecture / Seminar
    Time: 15:00-16:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Jorge Ferrer
    Organizer: Life Sciences

    From kB to kB: Universal and efficient entropy estimation using a compression algorithm

    Date:
    08
    Sunday
    April
    2018
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Roy Beck
    Organizer: Department of Materials and Interfaces
    Abstract: Entropy and free-energy estimation are key in thermodynamic characterization o ... Entropy and free-energy estimation are key in thermodynamic characterization of simulated systems ranging from spin models through polymers, colloids, protein structure, and drug-design. Current techniques suffer from being model specific, requiring abundant computation resources and simulation at conditions far from the studied realization. In this talk, I will present a novel universal scheme to calculate entropy using lossless compression algorithms and validate it on simulated systems of increasing complexity. Our results show accurate entropy values compared to benchmark calculations while being computationally effective. In molecular-dynamics simulations of protein folding, we exhibit unmatched detection capability of the folded states by measuring previously undetectable entropy fluctuations al