All upcoming events

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

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

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.

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.

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

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

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.

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

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

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

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

All Events

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: 09:30-10:30
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.

“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.

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

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

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: 12:00-13:00
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

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

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

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.

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: The 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
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.

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.

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 along the simulation timeline. Such entropy evaluation opens a new window onto the dynamics of complex systems and allows efficient free-energy calculations.

Clinical & Future Directions for Treatments of Prevalent Cancer Types - LUNG CANCER

Date:
29
Thursday
March
2018
Lecture / Seminar
Time: 11:15-13:00
Location: Max and Lillian Candiotty Building
Lecturer: Prof. Jair Bar
Organizer: Feinberg Graduate School

Improving breast cancer recurrence prediction and understanding using expression profiles and machine learning

Date:
26
Monday
March
2018
Lecture / Seminar
Time: 14:00-15:00
Title: Special Guest Seminar
Location: Max and Lillian Candiotty Building
Lecturer: Dr. Eitan Rubin
Organizer: Department of Biological Regulation

Double mutant cycles in the gas phase: measuring inter-protein pairwise interaction energies from crude cell lysates by native MS

Date:
20
Tuesday
March
2018
Lecture / Seminar
Time: 10:30-11:00
Location: Nella and Leon Benoziyo Building for Biological Sciences
Lecturer: Dr. Jelena Cveticanin
Organizer: Department of Biomolecular Sciences
Abstract: Double-mutant cycle analysis provides a strategy for studying the strength of pa ...Double-mutant cycle analysis provides a strategy for studying the strength of pairwise interactions within and between proteins. These pairwise interaction energies can be determined from a single native mass spectrum by measuring the intensities of the complexes formed by the two wild-type proteins, the complex of each wild-type protein with a mutant protein, and the complex of the two mutant proteins. This native mass spectrometry approach, obviates the need for error-prone measurements of binding constants, and provides information regarding multiple interactions in a single spectrum. Recently we advanced this MS-based approach to enable direct measurements from crude cell lysate of bacteria co-expressing the four proteins forming the cycle. This method overcomes the need for purifying the target proteins, providing an efficient and rapid mean of determining coupling energies.

The immune system of bacteria: CRISPR and beyond

Date:
13
Tuesday
March
2018
Lecture / Seminar
Time: 11:30
Location: Nella and Leon Benoziyo Building for Biological Sciences
Lecturer: Prof. Rotem Sorek
Organizer: Department of Plant and Environmental Sciences

Breast cancer heterogeneity - what, when and where?

Date:
12
Monday
March
2018
Lecture / Seminar
Time: 14:00-15:00
Title: Cancer Research Club Seminar
Location: Max and Lillian Candiotty Building
Lecturer: Prof. Carlos Caldas
Organizer: Department of Biological Regulation

Developmental Club Series 2017-2018

Date:
07
Wednesday
March
2018
Lecture / Seminar
Time: 10:00
Title: Human Brain Organoids on a Chip to Model Development and Disease
Location: Arthur and Rochelle Belfer Building for Biomedical Research
Lecturer: Prof. Orly Reiner
Organizer: Department of Molecular Genetics

“Dynamic recognition in protein-DNA complexes studied by simulations and experiments”

Date:
06
Tuesday
March
2018
Lecture / Seminar
Time: 14:00-15:00
Location: Helen and Milton A. Kimmelman Building
Lecturer: Prof. Carlos Simmerling
Organizer: Department of Structural Biology
Abstract: In contrast to proteins recognizing small-molecule ligands, DNA-dependent enzyme ...In contrast to proteins recognizing small-molecule ligands, DNA-dependent enzymes cannot rely solely on interactions in the substrate-binding centre to achieve their exquisite specificity. It is widely believed that substrate recognition by such enzymes involves a series of conformational changes in the enzyme-DNA complex with sequential gates favoring cognate DNA and rejecting nonsubstrates. However, direct evidence for such mechanism is limited to a few systems. We used molecular dynamics simulations to explore the dynamic recognition of oxidative DNA damage by glycosylase enzymes. The resulting energy profiles, supported by biochemical analysis of site-directed mutants disturbing the interactions along the proposed path, show that the glycosylases selectively facilitate recognition by stabilizing several intermediate states, helping the rapidly sliding enzyme avoid full extrusion of every encountered base for interrogation. Lesion recognition through multiple gating intermediates may be a common theme in DNA repair enzymes; we show that human and bacterial enzymes share a common recognition mechansim despite lack of sequence or structural similarity of their glycosylases.

Role of pituicytes, the resident astroglia of the neurohypophysis in neuro-vascular development

Date:
27
Tuesday
February
2018
Lecture / Seminar
Time: 12:30
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Gil Levkowitz
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 hypothalamo-neurohypophyseal system (HNS) is an evolutionarily conserved neu ...The hypothalamo-neurohypophyseal system (HNS) is an evolutionarily conserved neuroendocrine interface through which the brain regulates body homeostasis by means of releasing neuro-hormones (i.e. oxytocin and vasopressin) from the hypothalamus to the blood circulation. The basic components of the HNS are the hypothalamic axonal projections, endothelial blood vessels and astroglial-like cells, termed pituicytes. These three tissue types converge and interact at the ventral forebrain to establish an efficient neuro-vascular interface, which allows the release of neurohormones from the brain to the periphery. In contrast to BBB-containing CNS vessels, neurohypophyseal capillaries are permeable, which enables bypassing the BBB to transfer HNS hormones and blood-borne substances between brain and circulation. I will present our recent molecular and functional analysis that revealed a new role for pituicytes, in establishing a permeable neuro-vascular conduit that bypasses the BBB.

Novel innate immune checkpoint reveals the need to better consider the role of receptor splice variants

Date:
26
Monday
February
2018
Lecture / Seminar
Time: 14:00-15:00
Location: Max and Lillian Candiotty Building
Lecturer: Prof. Angel Porgador
Organizer: Department of Biological Regulation

From EPR to DNP: CP-Edited ENDOR and Liquid State DNP to Study Biomolecules

Date:
22
Thursday
February
2018
Lecture / Seminar
Time: 09:30
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Marina Bennati
Organizer: Department of Materials and Interfaces
Abstract: Addressing the issue of sensitivity has been a long-standing goal in magnetic re ...Addressing the issue of sensitivity has been a long-standing goal in magnetic resonance, continuously leading to new hardware development as well as the design of new excitation and detection schemes. Our contribution in this direction has been the investigation of two different types of polarization transfer mechanism between electron and nuclear spins, specifically the electron-nuclear cross-polarization (eNCP or CP) in the solid state1 and the Overhauser-type dynamic nuclear polarization in the liquid state. This lecture will give an overview on our recent insights and the application potential of these two methods in studies of biological systems. We have introduced eNCP in ENDOR spectroscopy to elucidate the mechanism of proton-coupled electron transfer (PCET) in the catalytic reaction of the prototype enzyme ribonucleotide reductase. Using combinations of 2H-Mims and CP-edited ENDOR in conjunction with quantum chemical calculations we succeeded in determining the hydrogen bond network around catalytic intermediates as well as the conformation of the amino tyrosyl radical, a probe generally used in PCET reactions.2 For studies in the liquid state, we recently observed that scalar electron -13C cross relaxation can lead to 13C NMR signal enhancements up to three orders of magnitude at various magnetic fields.3 These enhancements are consistent with theoretical predictions based on the available theory. Possible developments and applications of scalar Overhauser DNP will be discussed.

MICC cancer research workshop for clinical residents

Date:
21
Wednesday
February
2018
-
22
Thursday
February
2018
Conference
Time: 08:00
Location: Raoul and Graziella de Picciotto Building for Scientific and Technical Support
Organizer: The Moross Integrated Cancer Center (MICC)

Single-entity analysis at the nanoscale: Recent developments in electrochemistry

Date:
18
Sunday
February
2018
Lecture / Seminar
Time: 11:00-12:00
Location: Perlman Chemical Sciences Building
Lecturer: Dr. Enno Katelhon
Organizer: Department of Materials and Interfaces
Abstract: The nano-impact technique is among the latest and most considerable advances i ... The nano-impact technique is among the latest and most considerable advances in electrochemistry and enables the detection and characterisation of individual nanoparticles, viruses, and bacteria. Its significance particularly arises from the broad applicability and simplicity of the experimental set-up and procedure: An electrode is set in contact with a solution comprising a suspension of analyte particles and is biased versus the solution potential. By virtue of Brownian motion, individual analyte entities then stochastically impact on the electrode surface, where they give rise to transient currents, Faradaic or capacitive, and an analysis provides insight into the nature of the impacting entity as well as the prevalent reaction mechanism. The talk commences with a broad overview of the nano-impact technique while particularly theoretical aspects are highlighted. We then turn to examples of theoretical work on stochastic processes and the feasibility of individual enzyme detection to illustrate topics that are currently researched. In the light of recent developments, the talk finally points out future challenges and opportunities in the theory of nano-impacts.

Coordinated regulation of gut microbiota and immune checkpoint by RNF5 ubiquitin ligase

Date:
15
Thursday
February
2018
Lecture / Seminar
Time: 14:00-15:00
Title: Cancer Research Club
Location: Max and Lillian Candiotty Building
Lecturer: Prof. Zeev Ronai
Organizer: Department of Biological Regulation
Abstract: Growing evidence points to the importance of gut microbiome in tumor response to ...Growing evidence points to the importance of gut microbiome in tumor response to therapy, including immune checkpoint therapy. Yet, fundamental questions regarding the regulation of the gut microbiota and possible cross talk with immune checkpoint activity remains largely unexplored. Our work on the E3 ubiquitin ligase, which has been implicated in endoplasmic reticulum (ER)-associated protein degradation, led us to identify an unexpected link between the ligase and tumor growth, through fine tuning of gut microbiota and immune checkpoint activity. The nature of such coordinated regulation and its implications for cancer development, response to therapy and autoimmune disorders will be discussed.

G-INCPM Special Seminar - Prof. Yaakov Nahmias, Director, Grass Center for Bioengineering, Hebrew Univ., Jerusalem - "Beyond the Chip: Development of a Micro-Physiological Multi-Organ Flux Analyzer

Date:
14
Wednesday
February
2018
Lecture / Seminar
Time: 11:00-12:15
Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
Lecturer: Prof. Yaakov Nahmias
Organizer: Department of Biomolecular Sciences
Abstract: Organ-on-chip technology aims to replace animal toxicity testing, but thus far d ...Organ-on-chip technology aims to replace animal toxicity testing, but thus far demonstrated few advantages over traditional methods. Current methods to evaluate toxicity rely on end-point assays measuring tissue damage and cell death, resulting in limited kinetic and mechanistic information. We present the Tissue Dynamics platform capable of maintaining vascularized 3D liver, cardiac, and neural tissues for over a month in vitro. Tissues acquire physiological structure, physiological activity and show complex metabolic zonation. Tissue-embedded metabolic sensors for oxygen, glucose, lactate and glutamine permit the real-time quantification of intracellular fluxes and tissue level function. Change in metabolic function is the first indication of physiological stress, preceding any detectable damage. Using the Tissue Dynamics platform, we show a new CYP450-idependent mechanism of acetaminophen toxicity that may be responsible for clinically observed nephrotoxicity. We also show that troglitazone, a drug withdrawn from the market due to idiosyncratic toxicity, induces harmful metabolic changes at below the observed threshold for toxic damage. These metabolic changes may underlie troglitazone’s observed idiosyncratic toxicity. Our work marks the importance of tracing function in real-time, demonstrating specific advantages in predicative toxicology.

19F Magnetic Resonance Imaging: Unmasking Biomedical Hot Spots from the Background

Date:
08
Thursday
February
2018
Lecture / Seminar
Time: 09:30-10:30
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Ulrich Floegel
Organizer: Department of Materials and Interfaces
Abstract: This talk will focus on current developments in 19F MRI for molecular imaging ap ...This talk will focus on current developments in 19F MRI for molecular imaging applications. In the recent years, we and others demonstrated that 19F MRI is an excellent tool for non-invasive imaging of immune cell infiltration in a variety of clinically relevant disease models. For this purpose, biochemically inert perfluoro¬carbon nanoemulsions (PFCs) are employed, which are preferentially phagocytosed by circulating monocytes. After infiltration into inflammatory foci, these can be unequivocally identified as background-free hot spots by combined 1H/19F MRI. Recently, we proved that a specific, active targeting of PFCs to other structures like thrombi, platelets, human neutrophils or other individual cell populations is feasible as well. Furthermore, we developed an imaging technique for concurrent detection of different PFCs with distinct spectral signatures allowing the simultaneous visualization of several targets labelled with these PFCs (‘multicolor’ approach). Since ligands and targets can be easily adapted to a variety of problems, this approach provides a general and versatile platform for molecular imaging which strongly extends the frontiers of MRI, which is illustrated in several cardiovascular relevant settings. Future perspectives will include new strategies for tuning of specificity and sensitivity of 19F MRI.

Brain-immune interactions: from brain to gut

Date:
06
Tuesday
February
2018
Lecture / Seminar
Time: 12:30
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Dr. Asya Rolls
Organizer: Department of Neurobiology
Abstract: Increasing evidence indicates that the brain can control immunity. But how is th ...Increasing evidence indicates that the brain can control immunity. But how is the brain informed of the state of the immune response? What information is available to the brain regarding the immune system, and how do these essential systems communicate and interact? In this talk, I will try to bridge these gaps. I will demonstrate how specific activity in the brain affects the immune response, and how the peripheral nervous system can convey signals from the brain to the periphery to regulate immunity.

Chaos and Levy walks in swarming bacteria

Date:
05
Monday
February
2018
Lecture / Seminar
Time: 14:15
Location: Edna and K.B. Weissman Building of Physical Sciences
Lecturer: Gil Ariel
Organizer: Department of Physics of Complex Systems
Abstract: The "active" aspect of active matter, from the statistical-physics perspective, ...The "active" aspect of active matter, from the statistical-physics perspective, is the breaking of detailed balance in the microscopic dynamics. Hence, modelling of nonequilibrium microscopic conditions and their implications, such as the appearance of emergent equilibrium, is now active as a field of research. Recent theory studies and experiments with ultracold ions trapped in vacuum, make surprising contact with these questions; A fundamental model of transport in a noisy environment is that of the Brownian ratchet, or Brownian motor. It models the emergence of nonvanishing currents in a noisy system despite the vanishing of the mean force. Crucially based on symmetry breaking, it is a basic model for some of the physics underlying, e.g., biological molecular motors. I will discuss self-organized ion crystals featuring transport of ratchet-like discrete solitons. The rate and direction of selective topological-charge transport can be described as a Kramer's escape applied to a collective coordinate, with an emergent effective temperature [1]. If time permits, I will briefly discuss other relevant physics encountered with trapped ions - stochastic dynamics with single ions [2], and the simulation of microscopic friction models [3]. [1] J. Brox, P. Kiefer, M. Bujak, T. Schaetz (experiment), H. Landa (theory), PRL 119, 153602 (2017). [2] V. Roberdel, A. Maitra, D. Leibfried, D. Ullmo, and H. Landa, in preparation. [3] T. Fogarty, C. Cormick, H. Landa, V. M. Stojanović, E. Demler, and G. Morigi, PRL 115, 233602 (2015).

Neuroimaging in human drug addiction: an eye towards intervention development

Date:
05
Monday
February
2018
Lecture / Seminar
Time: 12:45
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Rita Z. Goldstein, PhD
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: Drug addiction is a chronically relapsing disorder characterized by compulsive d ...Drug addiction is a chronically relapsing disorder characterized by compulsive drug use despite catastrophic personal consequences (e.g., loss of family, job) and even when the substance is no longer perceived as pleasurable. In this talk, I will present results of human neuroimaging studies, utilizing a multimodal approach (neuropsychology, functional magnetic resonance imaging, event-related potentials recordings), to explore the neurobiology underlying the core psychological impairments in drug addiction (impulsivity, drive/motivation, insight/awareness) as associated with its clinical symptomatology (intoxication, craving, bingeing, withdrawal). The focus of this talk is on understanding the role of the dopaminergic mesocorticolimbic circuit, and especially the prefrontal cortex, in higher-order executive dysfunction (e.g., disadvantageous decision-making such as trading a car for a couple of cocaine hits) in drug addicted individuals. The theoretical model that guides the presented research is called iRISA (Impaired Response Inhibition and Salience Attribution), postulating that abnormalities in the orbitofrontal cortex and anterior cingulate cortex, as related to dopaminergic dysfunction, contribute to the core clinical symptoms in drug addiction. Specifically, our multi-modality program of research is guided by the underlying working hypothesis that drug addicted individuals disproportionately attribute reward value to their drug of choice at the expense of other potentially but no-longer-rewarding stimuli, with a concomitant decrease in the ability to inhibit maladaptive drug use. In this talk I will also explore whether treatment (as usual) and 6-month abstinence enhance recovery in these brain-behavior compromises in treatment seeking cocaine addicted individuals. Promising neuroimaging studies, which combine pharmacological (i.e., oral methylphenidate, or RitalinTM) and salient cognitive tasks or functional connectivity during resting-state, will be discussed as examples for using neuroimaging in the empirical guidance for the development of effective neurorehabilitation strategies (including cognitive training) in drug addiction.

When Lymphocytes

Date:
01
Thursday
February
2018
Lecture / Seminar
Time: 14:00-15:00
Title: Cancer Research Club
Location: Max and Lillian Candiotty Building
Lecturer: Prof. Eli Pikarsky
Organizer: Department of Biological Regulation
Abstract: Inflammation usually entails a diffuse influx of immune cells, scattered through ...Inflammation usually entails a diffuse influx of immune cells, scattered throughout the inflamed tissue. However, it can also form complex structures that histologically resemble lymphoid organs, referred to as ectopic lymphoid-like structures (ELSs). Using a mouse model forming hepatic ELSs we revealed that they can form protumorigenic immune niches, which foster growth of Hepatocellular carcinoma (HCC) progenitors. We are currently investigating the mechanisms that drive HCC formation in ELSs, as well as mechanisms that turn the ELS from an anti-tumor immune micro-organ into a protumorigenic one.

Joint Structural Biological and Magnetic Resonance Seminar

Date:
30
Tuesday
January
2018
Lecture / Seminar
Time: 14:30
Title: Solid-State NMR Studies of the Structure and Dynamics of an Influenza Membrane Protein for Proton Transport and Membrane Scission
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Mei Hong
Organizer: Department of Chemical and Biological Physics
Abstract: Membrane proteins carry out a myriad of biological functions such as ion conduct ...Membrane proteins carry out a myriad of biological functions such as ion conduction, substrate transport, and signaling. Solid-state NMR spectroscopy allows us to obtain exquisite atomic-level information of the structures and structural changes that underlie these functions. In this talk, I will present our investigations of the structure and dynamics of a multifunctional influenza virus membrane protein, matrix protein 2 (M2), which conducts protons and causes membrane scission. 13C, 15N, and 1H chemical shifts provided detailed information about pH-dependent conformational changes and equilibria between the open and closed states of the proton channel. Motionally averaged NMR spectra revealed microsecond-timescale dynamics of the proton-selective histidine and the gating tryptophan of the channel, while 2D exchange NMR spectra revealed millisecond-timescale dynamics of the entire tetrameric complex. Hydrogen bonding between water and the proton-selective histidine and proton exchange dynamics have been directly observed in 15N NMR spectra, giving insight into the atomic processes of proton transfer through the hydrated channel. In the second function, the M2 protein interacts with membrane cholesterol to cause scission of the emerging virus particle from the host cell in the final step of virus budding. By measuring 13C-19F distances between cholesterol and the protein, we determined the first cholesterol-binding site structure of a membrane protein in lipid bilayers. The structure gave unexpected insight into how M2 is attracted to the neck of the budding virus to cause membrane scission. Such intermolecular binding studies are crucially enabled by long-range distance constraints. We are exploring 19F-19F dipolar coupling measurements that probe distances up to 2 nm, to determine protein structures and protein-ligand interactions.

Noncoding RNA in Health and Disease

Date:
30
Tuesday
January
2018
Lecture / Seminar
Time: 10:00-11:00
Location: Arthur and Rochelle Belfer Building for Biomedical Research
Lecturer: Prof. Nikolaus Rajewsky
Organizer: The Azrieli Institute for Systems Biology

Molecular Genetics Departmental Seminars 2017-2018

Date:
28
Sunday
January
2018
Lecture / Seminar
Time: 13:00
Title: "Metabolic enzyme coupling of Malate Dehydrogenases is enabled by piggybacking to peroxisomes".
Location: Arthur and Rochelle Belfer Building for Biomedical Research
Lecturer: Shiran Maskit
Organizer: Department of Molecular Genetics

Personalized Nanomedicines: Principles for using nanotechnology in cancer research

Date:
28
Sunday
January
2018
Lecture / Seminar
Time: 11:00-12:00
Location: Perlman Chemical Sciences Building
Lecturer: Prof. Avi Schroeder
Organizer: Department of Materials and Interfaces
Abstract: Medicine is taking its first steps towards patient-specific care. Nanoparticle ... Medicine is taking its first steps towards patient-specific care. Nanoparticles have many potential benefits for treating cancer, including the ability to transport complex molecular cargoes including siRNA and protein, as well as targeting to specific cell populations. The talk will address principles for engineering drug-loaded nanoparticles that can be remotely triggered to release their payload in disease sites. The evolution of such nanoparticles into programmed nano robots, unique particles that have an internal capacity to synthesize protein drugs, and their promise for treating cancer, will be discussed. Our research is aimed at tailoring treatments to address each person’s individualized needs and unique disease presentation. Specifically, we developed barcoded nanoparticles that target sites of cancer where they perform a programmed therapeutic task. These systems utilize molecular-machines to improve efficacy and reduce side effects.

Optogenetic fMRI and the Investigation of Global Brain Circuit Mechanisms

Date:
25
Thursday
January
2018
Lecture / Seminar
Time: 14:00
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Jin Hyung Lee, PhD
Organizer: Department of Neurobiology
Details: Host: Dr.Ofer Yizhar ofer.yizhar@weizmann.ac.il tel: 6957 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
Abstract: Understanding the functional communication across brain has been a long sought-a ...Understanding the functional communication across brain has been a long sought-after goal of neuroscientists. However, due to the widespread and highly interconnected nature of brain circuits, the dynamic relationship between neuronal network elements remains elusive. With the development of optogenetic functional magnetic resonance imaging (ofMRI), it is now possible to observe whole-brain level network activity that results from modulating with millisecond- timescale resolution the activity of genetically, spatially, and topologically defined cell populations. ofMRI uniquely enables mapping global patterns of brain activity that result from the selective and precise control of neuronal populations. Advances in the molecular toolbox of optogenetics, as well as improvements in imaging technology, will bring ofMRI closer to its full potential. In particular, the integration of ultra-fast data acquisition, high SNR, and combinatorial optogenetics will enable powerful systems that can modulate and visualize brain activity in real-time. ofMRI is anticipated to play an important role in the dissection and control of network-level brain circuit function and dysfunction. In this talk, the ofMRI technology will be introduced with advanced approaches to bring it to its full potential, ending with examples of dissecting whole brain circuits associated with neurological diseases utilizing ofMRI. Short Bio: Dr. Lee received her Bachelor’s degree from Seoul National University and Masters and Doctoral degree from Stanford University, all in Electrical Engineering. She is a recipient of the 2008 NIH/NIBIB K99/R00 Pathway to Independence Award, 2010 NIH Director’s New Innovator Award, 2010 Okawa Foundation Research Grant Award, 2011 NSF CAREER Award, 2012 Alfred P. Sloan Research Fellowship, 2012 Epilepsy Therapy Project award, 2013 Alzheimer’s Association New Investigator Award, 2014 IEEE EMBS BRAIN young investigator award, and the 2017 NIH/NIMH BRAIN grant award. As an Electrical Engineer by training with Neuroscience research interest, her goal is to analyze, debug, and engineer the brain circuit through innovative technology. 1. Hyun Joo Lee†, Andrew Weitz†, David Bernal-Casas, Ben A. Duffy, Mankin Choy, Alexxai Kravitz, Anatol Kreitzer, Jin Hyung Lee*, Activation of direct and indirect pathway medium spiny neurons drives distinct brain-wide responses, Neuron, 2016;91(2):412-424. 2. Jia Liu†, Ben A. Duffy†, David Bernal-Casas, Zhongnan Fang, Jin Hyung Lee*, Comparison of fMRI analysis methods for heterogeneous BOLD responses in block design studies, Neuroimage, 2017;147:390-408. 3. David Bernal-Casas, Hyun Joo Lee, Andrew Weitz, Jin Hyung Lee*, Studying brain circuit function with dynamic causal modeling for optogenetic fMRI, Neuron, 2017;93:522-532.

Developmental Club Series 2017-2018

Date:
24
Wednesday
January
2018
Lecture / Seminar
Time: 10:00
Title: How a key interface between the brain’s neuro-hormonal and vascular systems is assembled
Location: Arthur and Rochelle Belfer Building for Biomedical Research
Lecturer: Prof. Gil Levkowitz
Organizer: Department of Molecular Genetics

A deep 3D view into cells using cryo-scanning transmission electron tomography

Date:
23
Tuesday
January
2018
Lecture / Seminar
Time: 10:00-11:00
Location: Nella and Leon Benoziyo Building for Biological Sciences
Lecturer: Dr. Shron G. Wolf
Organizer: Department of Biomolecular Sciences
Abstract: CryoSTEM tomography (CSTET) is a novel combination [1-5] of two well-established ...CryoSTEM tomography (CSTET) is a novel combination [1-5] of two well-established techniques: cryo-electron tomography (CET) and scanning transmission electron microscopy (STEM). Cryogenic fixation allows for the most faithful preservation of biological macromolecules, tissues and cells. By preserving the cryogenic temperature and maintaining a contamination-free environment inside the electron microscope, CET for such cryo-preserved specimens have resulted in major advances in their characterization [6]. However, due to technical constraints, sample thickness amenable to viewing by CET is limited (up to ~400 nm). STEM provides a possibility for relieving these limitations because contrast and signal are produced incoherently. The natural limit for sample thickness is extended three-fold for CSTET, meaning that whole vitrified mammalian cells can be imaged at ~3-4 nm resolution for regions up to ~1 μm in thickness. For spreading cells, many inter- organelle contacts and morphologies can be studied. In addition, CSTET combined with Energy Dispersive X-ray Spectroscopy (EDX) allows for on-the-spot chemical characterization of cell contents. References 1. Wolf, S.G., L. Houben, and M. Elbaum, Cryo-scanning transmission electron tomography of vitrified cells. Nature Methods, 2014. 11(4): p. 423-428. 2. Wolf, S.G., P. Rez, and M. Elbaum, Phosphorus detection in vitrified bacteria by cryo- STEM annular dark-field analysis. J Microsc, 2015. 260(2): p. 227-33. 3. Elbaum, M., S.G. Wolf, and L. Houben, Cryo-scanning transmission electron tomography of biological cells. MRS Bulletin, 2016. 41(07): p. 542-548. 4. Wolf, S.G., E. Shimoni, M. Elbaum, and L. Houben, STEM Tomography in Biology, in Cellular Imaging, Electron Tomography and Related Techniques, E.G. Hanssen, Editor. 2017, Springer, in press. 5. Wolf, S.G., Y. Mutsafi, T. Dadosh, T. Ilani, Z. Lansky, B. Horowitz, S. Rubin, M. Elbaum, and D. Fass, 3D visualization of mitochondrial solid-phase calcium stores in whole cells. Elife, 2017. 6: e29929. 6. Beck, M. and W. Baumeister, Cryo-Electron Tomography: Can it Reveal the Molecular Sociology of Cells in Atomic Detail? Trends Cell Biol, 2016. 26(11): p. 825-837.

Functions and regulation of 3D genome organisation in development and disease

Date:
23
Tuesday
January
2018
Lecture / Seminar
Time: 10:00-11:00
Location: Arthur and Rochelle Belfer Building for Biomedical Research
Lecturer: Prof. Francois Spitz
Organizer: The Azrieli Institute for Systems Biology
Abstract: The complex hierarchy of three-dimensional patterns that characterize the 3D fol ...The complex hierarchy of three-dimensional patterns that characterize the 3D folding of mammalian chromosomes appears as an important element in controlling gene expression. At the megabase scale, chromosomes are partitioned into domains that define two main compartments, corresponding to transcriptionally active and inactive regions, respectively. Each compartment domain is itself composed of distinct domains characterized by increased self-interactions called topological domains (TADs). Recent high-resolution Hi-C approaches revealed a finer-scale organisation of the genome in smaller “contact domains”, often associated with loops linking specific points. At these different scales, the spatial organisation of the genome shows tight correlation with its chromatin structure and its transcriptional activity. However, while steady progress is being made in describing the 3D folding of the genome at increased resolution, the mechanisms that determine this folding, its dynamic properties and the functional implications of these emerging features are still poorly understood. We use advanced genome tagging and engineering strategies, as well as targeted inactivation of factors involved in chromosomal folding to unravel the elements and mechanisms that drive the folding of large loci in specific yet dynamic conformations and their influence on gene expression. Our recent results show that the complex patterns of vertebrate HiC maps result from the superimposition of two distinct mechanisms: 1) a cohesin-independent mechanism which brings together regions of similar chromatin states 2) a cohesin-dependent folding that associate different small compartments into TADs. Within TADS, we show as well that enhancers are not acting in a homogeneous manner, but that their influence is distributed in complex patterns, partially guided by the underlying structure. I will discuss the different implications of these findings for our views of genome organisation.

Bacterial transcription initiation gone awry: backtracking and pausing that lasts for durations comparable to the bacterial lifespan

Date:
22
Monday
January
2018
Lecture / Seminar
Time: 14:00-15:00
Title: Special Guest Seminar
Location: Max and Lillian Candiotty Building
Lecturer: Dr. Eitan Lerner
Organizer: Department of Biological Regulation
Abstract: DNA transcription follows a chain of events: initiation, elongation and terminat ...DNA transcription follows a chain of events: initiation, elongation and termination, in which initiation usually the slowest. This is mainly due to the process of RNA-polymerase (RNAP) proper binding to the promoter region on DNA and formation of the open transcription bubble, but also due to many failed attempts of the initially-transcribing complex (ITC) to escape the promoter region and transition to elongation. The latter involves multiple polymerization rounds of short transcript that are depleted from the complex after RNAP aborts a transcription trial to try again (abortive initiation). Traditionally, each round of abortive initiation was thought to be rapid. Using single-molecule FRET as well as magnetic tweezers nanomanipulation tools we have recently discovered an abortive initiation intermediate in which a short transcript on its way to be depleted, stabilizes the complex in a unique conformation with blockage of the nucleotide entry channel (the secondary channel). Even more intriguing was the fact that this paused-backtracked initiation intermediate was stabilized for ~4600 s. In addition, using single-molecule FRET measurements of multiple distances, we show that this long-lived paused-backtracked intermediate is associated with a conformation in the DNA transcription bubble different than any existing determined structure of the bacterial transcription initiation complex. Additionally, the initiation complex in this intermediate state avoids inhibition by the antibiotic molecule Rifampicin, for which there exist many different antibiotic-resistant mutants of RNAP. Therefore, it is important to understand how to stabilize this long-lived paused state as an antimicrobial strategy. This requires further structural determination, and because this intermediate state is heterogeneous, hence very hard to resolve using traditional structural biological techniques, we will discuss ways to resolve the possible structure through hybrid/integrative structural techniques, combining single-molecule spectroscopy and coarse-grained simulations. These findings open a new avenue in studying the mechanism of bacterial transcription initiation as well as new molecular therapeutic routes.

The 3rd meeting of the Israeli Breast Cancer Translational Research Group

Date:
18
Thursday
January
2018
Conference
Time: 08:00
Location: David Lopatie Conference Centre
Organizer: Moross Research School of Mathematics and Computer Science,Faculty of Biochemistry,Faculty of Biology

Prof. Rotem Sorek - Viruses that attack bacteria – friend or foe?

Date:
16
Tuesday
January
2018
Lecture / Seminar
Time: 12:00
Title: Viruses that attack bacteria – friend or foe?
Location: Dolfi and Lola Ebner Auditorium
Lecturer: Prof. Rotem Sorek
Organizer: Department of Media Relations
Details: The lecture is in Hebrew