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    Special Guest Seminar

    Date:
    12
    Tuesday
    November
    2024
    Lecture / Seminar
    Time: 11:00-12:00
    Title: EV-DNA Drives Anti-Tumor Immunity and Inhibits Metastasis
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Inbal Wortzel
    Organizer: Department of Immunology and Regenerative Biology
    Contact: rony.seger@weizmann.ac.il

    Israeli Conference on Protein-DNA interactions 2024

    Date:
    26
    Thursday
    September
    2024
    Conference
    Time: 08:00
    Location: The David Lopatie Conference Centre
    Organizer: Clore Center for Biological Physics,Braginsky Center for the Interface between Science and the Humanities,Weizmann School of Science
    Contact: vladimir.mindel@weizmann.ac.il

    From the lab to the clinic: A toolbox for single-molecule epigenetic analysis of DNA

    Date:
    18
    Tuesday
    June
    2024
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Yuval Ebenstein
    Organizer: Department of Biomolecular Sciences
    Contact: levana.ayvazo@weizmann.ac.il
    Abstract: Short-read DNA sequencing (NGS) is revolutionizing all fields of biological rese ... Read more Short-read DNA sequencing (NGS) is revolutionizing all fields of biological research. Still, it fails to extract the full range of information associated with genetic material and cannot resolve many variations between genomes. The information content of the genome extends beyond the base sequence in the form of chemical modifications such as DNA methylation, damage lesions, or chromosomal association with DNA-binding proteins (chromatin). For the last decade, our lab has been developing tools for genomic analysis at the single-cell and single-molecule levels. I’ll present a biochemical and physical toolbox for mapping epigenetic modifications in the genome and demonstrate its application in clinical cancer research.
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    Physics Colloquium

    Date:
    16
    Thursday
    May
    2024
    Colloquium
    Time: 11:15-12:30
    Title: Toward Autonomous “Artificial Cells” in 2D
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Prof. Roy Bar-Ziv,Weizmann Institute of Science
    Organizer: Department of Physics of Complex Systems
    Contact: eti.shalem@weizmann.ac.il
    Details: Refreshments at 11:00
    Abstract: We study the assembly of programmable quasi-2D DNA compartments as “artificia ... Read more We study the assembly of programmable quasi-2D DNA compartments as “artificial cells” from the individual cellular level to multicellular communication. We will describe work on autonomous synthesis and assembly of cellular machines, collective modes of synchrony in a 2D lattice of ~1000 compartments, and a first look at the birth of proteins on a single DNA.
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    RNA transmission between honeybees and their microbiome

    Date:
    02
    Thursday
    May
    2024
    Lecture / Seminar
    Time: 15:00-16:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Eyal Maori
    Organizer: Department of Biomolecular Sciences
    Contact: levana.ayvazo@weizmann.ac.il
    Abstract: Transmissible RNA has emerged as a means of communication between organisms, bot ... Read more Transmissible RNA has emerged as a means of communication between organisms, both within and across different kingdoms of life. Donor organisms transmit long base-paired RNA, tRNA-fragments, and other small RNAs to elicit RNAi responses in recipient individuals, affecting their gene expression and phenotypes. Honeybees offer a unique opportunity to study RNA transmission since they possess a transmissible RNA pathway through which they share RNAs between individuals and across generations via the secretion and ingestion of worker- and royal jelly. We hypothesised that members of the gut microbiome exploit the same pathway and transmit RNA to their honeybee host. We show that RNA originating from a gut-restricted bacterium, Snodgrassella alvi (S. alvi), can be detected in worker- and royal jellies. Endogenous S. alvi RNAs are present also in systemic larval tissues in the absence of bacterial genomic DNA, indicating jelly-mediated microbiome RNA uptake and systemic spread within recipient larvae. Characterisation of transmissible S. alvi RNA reveals enrichment of specific rRNA and tRNA fragments in systemic larval tissues. The transmitted RNA fragments could potentially be involved in RNAi and have the capacity to target honeybee pathogens, such as Nosema and viruses. An expanded transmissible RNA pathway and its potential cooperative roles in honeybee- microbiome interactions will be discussed.
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    A DNA methylation atlas of normal human cell types

    Date:
    18
    Thursday
    April
    2024
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Tommy Kaplan
    Organizer: Dwek Institute for Cancer Therapy Research
    Contact: michalav@weizmann.ac.il
    Details: For joining remotely please use Zoom: https://weizmann.zoom.us/j/5065402023?pwd= ... Read more For joining remotely please use Zoom: https://weizmann.zoom.us/j/5065402023?pwd=a3Z6KzRCU0xJaUFoM2Y5emZwZm1oZz09
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    Toward Autonomous “Artificial Cells” in 2D

    Date:
    11
    Thursday
    April
    2024
    Colloquium
    Time: 11:15-12:30
    Title: Physics colloquium
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Prof. Roy Bar-Ziv
    Organizer: Department of Physics of Complex Systems
    Contact: eti.shalem@weizmann.ac.il
    Details: Refreshments at 11:00
    Abstract: We study the assembly of programmable quasi-2D DNA compartments as “artificial ... Read more We study the assembly of programmable quasi-2D DNA compartments as “artificial cells”, from the individual cellular level to multicellular communication. We will describe work on autonomous synthesis and assembly of cellular machines, collective modes of synchrony in a 2D lattice of ~1000 compartments, and a first look at the birth of proteins on a single DNA.
    Close abstract

    What Funga can teach us about DNA repair

    Date:
    09
    Tuesday
    April
    2024
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Shay Covo
    Organizer: Department of Chemical and Structural Biology
    Contact: nicole.dorfman@weizmann.ac.il

    Inheritance of extrachromosomal DNA in cancer cells

    Date:
    09
    Tuesday
    April
    2024
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Inbar Lifshits
    Organizer: Department of Biomolecular Sciences
    Contact: levana.ayvazo@weizmann.ac.il
    Details: Inbar Lifshits Dept. of Biomolecular Sciences - WIS
    Abstract: Gene amplification contributing to tumorigenesis and therapy resistance is fre ... Read more Gene amplification contributing to tumorigenesis and therapy resistance is frequently observed across many cancer types. Amplifications of up to 100’s of oncogene DNA copies can be found within chromosomes in homogenous staining regions (HSRs), or in extrachromosomal DNA (ecDNA) elements (also known as double-minutes or DMs). Amplified genes can be oncogenes such as MYCN but they can also be genes that contribute to therapy resistance. For example, amplification of dihydrofolate reductase (DHFR) can lead to methotrexate (MTX) resistance. DMs are acentric and therefore randomly segregate into daughter cells, thereby driving intra-tumor heterogeneity and increasing gene copy number under selection. Although DMs appear to tether to chromosomes during mitosis, the mechanism underlying their inheritance is not clear. Previous works described tethering based on a few observations and in a very limited manner. This work aimed to extensively examine DM tethering at specific mitosis stages. In addition, the effect of anti-cancer therapies, including DNA damaging agent and microtubule drugs was examined. Elucidating the mechanism of DM tethering could provide insight into the inheritance of other acentric DNA molecules, including DNA from viral sources.
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    M.Sc. Thesis Defense Seminar

    Date:
    04
    Thursday
    April
    2024
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Inference of environmental factors across biomes using community-wide DNA composition
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Tomer Antman
    Organizer: Department of Plant and Environmental Sciences
    Contact: tomer.antman@weizmann.ac.il

    The interplay of bulky DNA damages, transcription and epigenetics

    Date:
    25
    Thursday
    January
    2024
    Lecture / Seminar
    Time: 15:00-16:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Sheera Adar
    Organizer: Department of Biomolecular Sciences
    Contact: levana.ayvazo@weizmann.ac.il
    Details: Host: Pof.Zvi Livneh
    Abstract: DNA damages compromise the ability of the genome to function. Cells from all org ... Read more DNA damages compromise the ability of the genome to function. Cells from all organisms have mechanisms to recognize DNA damage, initiate a signaling response, and recruit repair enzymes. Complete failure of these mechanisms leads to cell death. Incorrect or inefficient repair leads to mutations and cancer. Our work focuses on damages that distort the DNA helix, specifically the carcinogenic dimers induced by ultraviolet (UV) radiation, and the bulky DNA adducts induced by cigarette smoke and by the chemotherapy drug cisplatin. These types of damages are especially deleterious as they block RNA and DNA polymerases. We apply genomic methods to map DNA damages and their repair at high resolution in human genomes. In parallel, we study the effects of damage on gene expression and chromatin accessibility. Both chromatin structure and transcription influence the sensitivity to damage and the efficiency of repair. At the same time, damages elicit changes in chromatin accessibility and a dramatic gene expression shutdown. In my talk, I will give an overview of ongoing research projects in our lab that study the cellular responses to UV-, smoking- and cisplatin-induced damages, and are central to understanding both the carcinogenic process and the mechanisms of chemotherapy resistance.
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    The Clore Center for Biological Physics

    Date:
    21
    Sunday
    January
    2024
    Lecture / Seminar
    Time: 13:15-14:15
    Title: How informative are structures of dna-bound proteins for revealing binding mechanisms inside cells? the case of the Origin of Replication Complex (ORC)
    Location: Nella and Leon Benoziyo Physics Building
    Lecturer: Prof. Naama Barkai,Prof. Naama Barkai
    Organizer: Department of Physics of Complex Systems
    Contact: malka.avraham@weizmann.ac.il
    Details: Lunch at 12:45
    Abstract: The Origin Recognition Complex (ORC) seeds the replication-fork by binding DNA r ... Read more The Origin Recognition Complex (ORC) seeds the replication-fork by binding DNA replication origins, which in budding yeast contain a 17bp DNA motif. High resolution structure of the ORC-DNA complex revealed two base-interacting elements: a disordered basic patch (Orc1-BP4) and an insertion helix (Orc4-IH). To define ORC elements guiding its DNA binding in-vivo, we mapped genomic locations of 38 designed ORC mutants. We revealed that different ORC elements guide binding at different motifs sites, and these correspond only partially to the structure- described interactions. In particular, we show that disordered basic patches are key for ORC-motif binding in-vivo, including one lacking from the structure. Finally i will discuss how those disordered elements, which insert into the minor-groove can still guide specific ORC-DNA recognition.
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    The Clore Center for Biological Physics

    Date:
    14
    Sunday
    January
    2024
    Lecture / Seminar
    Time: 13:15-14:15
    Title: Kinetic Choreography: Exploring Protein-DNA Interactions Beyond Affinity & Specificity
    Location: Nella and Leon Benoziyo Physics Building
    Lecturer: Prof. Koby Levy
    Organizer: Clore Center for Biological Physics
    Contact: Ariel.amir@weizmann.ac.il
    Abstract: The kinetics of protein–DNA recognition, along with its thermodynamic properti ... Read more The kinetics of protein–DNA recognition, along with its thermodynamic properties, including affinity and specificity, play a central role in shaping biological function. Protein–DNA recognition kinetics are characterized by two key elements: the time taken to locate the target site amid various nonspecific alternatives; and the kinetics involved in the recognition process, which may necessitate overcoming an energetic barrier. In my presentation, I will describe the complexity of protein-DNA kinetics obtained from molecular coarse-grained simulations of various protein systems. The kinetics of protein-DNA recognition are influenced by various molecular characteristics, frequently necessitating a balance between kinetics and stability. Furthermore, protein-DNA recognition may undergo evolutionary optimization to accomplish optimal kinetics for ensuring proper cellular function.
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    Ph.D. Defense Seminar

    Date:
    04
    Monday
    September
    2023
    Lecture / Seminar
    Time: 11:30-12:30
    Title: The reasons behind better DNA preservation in the petrous bone: cellular and 3D structural analysis of modern pig and ancient human petrous bones
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Jamal Ibrahim
    Organizer: Scientific Archeology Unit
    Contact: jamal.ibrahim@weizmann.ac.il
    Details: The seminar will be also via zoom: Meeting ID: 940 5265 6196 Meeting password: 449244

    Liquid Biopsies and Circulating Free DNA in Cancer

    Date:
    03
    Monday
    July
    2023
    Lecture / Seminar
    Time: 11:15-12:00
    Location: Wolfson Building for Biological Research
    Lecturer: Prof. Yuval Dor
    Organizer: Weizmann School of Science
    Contact: levana.ayvazo@weizmann.ac.il
    Details: Host: Zvi Livneh

    “ Spatiotemporal considerations of DNA damage and repair in the biogenesis of gene amplification in cancer”

    Date:
    16
    Tuesday
    May
    2023
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Yifat Bar Or Snarski
    Organizer: Department of Biomolecular Sciences
    Contact: levana.ayvazo@weizmann.ac.il

    Soft Matter and Biomaterials Seminar: Cytoskeletal dynamics generate active liquid-liquid phase separation.

    Date:
    30
    Sunday
    April
    2023
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Alexandra Tayar
    Organizer: Department of Molecular Chemistry and Materials Science
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Liquid-Liquid phase separation (LLPS) has been of fundamental importance in the ... Read more Liquid-Liquid phase separation (LLPS) has been of fundamental importance in the assembly of thermally driven materials and has recently emerged as an organizational principle for living systems. Biological phase separation is driven out of equilibrium through complex enzyme composition, chemical reactions, and mechanical activity, which reveals a gap in our understanding of this fundamental phenomenon. Here we study the impact of mechanical activity on LLPS. We design a DNA-based LLPS system coupled to flows through molecular motors and a cytoskeleton network. Active stress at an interface of a liquid droplet suppressed phase separation and stabilized a single-phase regime well beyond the equilibrium binodal curve. The phase diagram out of equilibrium revealed a 3-dimensional phase space that depends on temperature and local molecular activity. Similar dynamics and structures are observed in simulations, suggesting that suppression of liquid phase separation by active stress is a generic feature of liquid phase separation.
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    Fast and Processive Artificial Molecular Motors and Rotors Made of DNA

    Date:
    28
    Tuesday
    February
    2023
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Eyal Nir
    Organizer: Department of Chemical and Structural Biology
    Contact: nicole.dorfman@weizmann.ac.il

    Microsecond Structural Dynamics of Protein, DNA and RNA Revealed by Two-Dimensional Fluorescence Lifetime Correlation Spectroscopy (2D FLCS)

    Date:
    30
    Monday
    January
    2023
    Colloquium
    Time: 11:00-12:15
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Tahei Tahara
    Organizer: Faculty of Chemistry
    Contact: sarah.amzallag@weizmann.ac.il
    Abstract: Single-molecule spectroscopy, combined with fluorescence resonance energy transf ... Read more Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, has been intensively utilized for studying the structural dynamics of protein, DNA, and RNA. However, observation of the dynamics on the microsecond timescale is challenging due to the low efficiency of collecting photons from a single molecule. To realize quantitative investigations of structural dynamics with a sub-microsecond time resolution, we developed new single-molecule spectroscopy, i.e., two-dimensional fluorescence lifetime correlation spectroscopy (2D FLCS). In this 2D FLCS, we use a high-repetition short pulse laser for photoexcitation and analyze the correlation of the fluorescence lifetime from the donor of a FRET pair. The obtained information is represented in the form of a 2D fluorescence lifetime correlation map using the inverse Laplace transform. 2D FLCS can visualize the structural dynamics of complex molecules in the equilibrium condition with a sub-microsecond resolution at the single-molecule level. In this presentation, I will talk about the principle of 2D FLCS and its application to the study of the structural dynamics of protein, DNA, and RNA, in particular, the most recent study on the folding/unfolding dynamics of an RNA riboswitch. Based on the observed microsecond folding dynamics, we proposed the molecular-level mechanism for transcription control by the riboswitch.
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    Microsecond Structural Dynamics of Protein, DNA and RNA Revealed by Two-Dimensional Fluorescence Lifetime Correlation Spectroscopy (2D FLCS) Colloquium website

    A direct MS approach for identifying damaged DNA in cancerous cells

    Date:
    20
    Tuesday
    December
    2022
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Joanna Stimpson
    Organizer: Department of Biomolecular Sciences
    Contact: levana.ayvazo@weizmann.ac.il
    Abstract: DNA can be damaged by chemicals in our surroundings, and occurs at the nucleophi ... Read more DNA can be damaged by chemicals in our surroundings, and occurs at the nucleophilic sites on the strand. Of particular interest is alkylation at the O6-position of guanine, which goes on to cause G:C -> A:T mutations. These mutations cause genomic instability and are linked to the onset of colorectal cancer (CRC). Identifying the extent and diversity of O6-guanine alkylation informs us on the exposure cancer patients have undergone. Here we have developed a mass spectrometry based approached to identify damaged DNA. The method is based on the DNA repair protein MGMT, which directly removes alkylation from O6-alkyl guanine. MGMT can be used to probe the type and extent of O6-alkylation.
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    One possible reason why the petrous bone preserves ancient DNA relatively well is that it contains high concentrations of bone cells

    Date:
    15
    Thursday
    December
    2022
    Lecture / Seminar
    Time: 13:30
    Location: Room 590, Benoziyo Building for Biological Science, Weizmann Institute of Science
    Lecturer: Jamal Ibrahim
    Contact: harsh.raj@weizmann.ac.il
    Details: Join Zoom Meeting: https://weizmann.zoom.us/j/4845901524?pwd=dkYybWIvTXVSaW40Ym ... Read more Join Zoom Meeting: https://weizmann.zoom.us/j/4845901524?pwd=dkYybWIvTXVSaW40YmF2TEVxVFg0UT09 Meeting ID: 484 590 1524 Meeting password: 045940
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    Chemical and Biological Physics Guest seminar

    Date:
    29
    Tuesday
    November
    2022
    Lecture / Seminar
    Time: 14:00
    Title: Playing the evolution game with DNA oligomers
    Location: Stone Administration Building
    Lecturer: Prof Tommaso Bellini
    Organizer: Department of Chemical and Biological Physics
    Contact: nir.gov@weizmann.ac.il
    Abstract: We introduce a variant of SELEX in-vitro selection to study the evolution of a p ... Read more We introduce a variant of SELEX in-vitro selection to study the evolution of a population of oligonucleotides starting from a seed of random-sequence DNA 50mers (our evolving individuals) and introducing selectivity by an affinity capture gel formed by beads carrying DNA 20mers of fixed sequence that act as targets (our resources). We PCR amplify the captured strands and proceed to the next generation. Because of the simplicity of the process, we could investigate what plays the role of “fitness" in this synthetic evolution process. We find that, across generations, evolution is first driven by the need of binding to the capture gel, while, on a later stages it appear dominated by the emerging of motifs related to inter-individual interactions.
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    Protein-DNA interactions: from biophysics to cell biology

    Date:
    18
    Tuesday
    October
    2022
    -
    20
    Thursday
    October
    2022
    Conference
    Time: 08:00 - 18:00
    Location: The David Lopatie Conference Centre
    Contact: lior.drori@weizmann.ac.il
    Protein-DNA interactions: from biophysics to cell biology Conference website

    Special guest seminar with Dr. Or Shemesh

    Date:
    28
    Tuesday
    June
    2022
    Lecture / Seminar
    Time: 09:30-10:30
    Title: Infectious Neuroscience - Do Common Pathogens Play a Part in Neurodegeneration?
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Dr. Or Shemesh
    Organizer: Department of Molecular Neuroscience
    Contact: Bosmat.kariti@weizmann.ac.il
    Abstract: Herpes Simplex Virus 1 (HSV-1) is a usual suspect when it comes to Alzheimer's d ... Read more Herpes Simplex Virus 1 (HSV-1) is a usual suspect when it comes to Alzheimer's disease (AD), and its DNA and RNA were found in the brains and serological samples of AD patients. Such molecular presence of HSV-1 in AD is especially intriguing as HSV-1 virions are rarely detected in AD brains. To follow the molecular footsteps detected, we imaged viral proteins in postmortem human AD brains at superior resolution using expansion microscopy, a tissue manipulation method that physically expands the samples by a factor of 4.5x, allowing a 40 nm imaging resolution, and immunolabeled herpetic proteins, AD pathologies and cell markers. We found an abundance of herpetic proteins, previously undetectable with standard methods, across large brain areas. Importantly, we found that HSV-1 proteins strongly co-localized with AD pathologies. Consequently, we hypothesized that expression of HSV-1 proteins during latency may be linked to AD pathology. We are now in the process of characterizing the HSV-1 proteome in AD brains by imaging key proteins in expanded AD brain slices and examining their colocalization with AD pathologies across brain areas and disease stages. As a complementary system to the fixed human brain slices, we are exposing live human brain organoids, to HSV-1, and imaging the relationships between viral proteins and the formation of AD pathologies via expansion microscopy. Pathogens may be triggers of immune responses driving AD; this study would shed light on one common pathogen, HSV-1, while serving as a framework to unveiling molecular causation between infectious agents and AD hallmarks.
    Close abstract

    Deep Learning Methods Reveal Structural Mechanisms of Protein-DNA Readout

    Date:
    14
    Tuesday
    June
    2022
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Remo Rohs
    Organizer: Department of Chemical and Structural Biology
    Contact: nicole.dorfman@weizmann.ac.il

    Promiscuous Translesion DNA Synthesis in Embryonic Stem Cells

    Date:
    14
    Tuesday
    June
    2022
    Lecture / Seminar
    Time: 10:30-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Ido Dromi
    Organizer: Department of Biomolecular Sciences
    Contact: levana.ayvazo@weizmann.ac.il

    Molecular Analysis of Translesion DNA Synthesis Under Hypoxia

    Date:
    14
    Tuesday
    June
    2022
    Lecture / Seminar
    Time: 10:00-10:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Ran Yehuda
    Organizer: Department of Biomolecular Sciences
    Contact: levana.ayvazo@weizmann.ac.il

    BRD4 in Transcription Programming and Cancer Therapy

    Date:
    26
    Thursday
    May
    2022
    Lecture / Seminar
    Time: 10:30-11:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Cheng-Ming Chiang
    Organizer: Department of Biomolecular Sciences
    Contact: levana.ayvazo@weizmann.ac.il
    Abstract: Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator and transcrip ... Read more Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator and transcription cofactor whose phosphorylation by casein kinase II (CK2) and dephosphorylation by protein phosphatase 2A (PP2A) modulates its function in gene-specific targeting and recruitment of transcriptional regulators and chromatin modifiers. BRD4 has emerged as an important cancer therapeutic target due to widely available small compound inhibitors, such as JQ1 and I-BET, targeting the bromodomain and extra-terminal (BET) family members. Besides transcriptional regulation, BRD4 also plays crucial roles in regulating diverse cellular processes, including cell cycle progression, DNA damage response, chromatin structure maintenance, stem cell reprogramming, cell lineage differentiation, and viral latency and reactivation. While BET inhibitors and degraders show promising anticancer effects, issues related to drug resistance upon prolonged treatment remain a challenge in BET-targeted therapeutics development. Recently, we identified specific small compound inhibitors targeting phosphorylation-dependent BRD4 interaction with distinct transcription/replication components and DNA damage response (DDR) factors, including p53, c-Myc, AP-1, and cancer-associated human papillomavirus E2 proteins. Some of these compounds effectively block cancer cell growth and migration and specifically inhibit p53 interaction with BRD4. These new types of protein-protein interaction (PPI) inhibitors highlight molecular action distinct from the widely used BET bromodomain inhibitors.
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    Seminar for Thesis Defense

    Date:
    11
    Wednesday
    May
    2022
    Lecture / Seminar
    Time: 14:00-15:00
    Title: "A short non-coding HBV RNA region upregulates R2 by eliciting the cellular DNA damage response"
    Location: Botnar Auditorium. Belfer building & zoom
    Lecturer: Karin Broennimann
    Organizer: Department of Molecular Genetics
    Contact: evi.ben-ami@weizmnn.ac.il
    Details: Zoom link: https://weizmann.zoom.us/j/97203659707?pwd=WE80NG5ldHEzblowQjlvWE5rT ... Read more Zoom link: https://weizmann.zoom.us/j/97203659707?pwd=WE80NG5ldHEzblowQjlvWE5rTDRvUT09 Meeting ID: 972 0365 9707 Password: 631000
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    Probing Biomolecular Dynamics with Single-Molecule Spectroscopy

    Date:
    02
    Monday
    May
    2022
    Colloquium
    Time: 11:00-12:15
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Hagen Hofmann
    Organizer: Faculty of Chemistry
    Contact: sarah.amzallag@weizmann.ac.il
    Abstract: Explaining organisms in terms of the jiggling and wiggling of atoms is a central ... Read more Explaining organisms in terms of the jiggling and wiggling of atoms is a central goal in molecular biology. Yet, the dynamics of proteins with their sophisticated three-dimensional architectures exceeds the capabilities of
analytical theories. On the other
hand, intrinsically
disordered proteins are often well described by polymer theories of different flavors. However, these theories do not apply to proteins in which disorder and order mix. Combining structural biology with polymer theory is therefore required to understand such biomolecules. I will discuss how optical single-molecule spectroscopy allows us to probe the dynamics of (partially) disordered proteins and complexes from nanoseconds to milliseconds. I will show how many weak protein-protein interactions can cause rugged energy landscapes that slow-down dynamics by orders of magnitude. In the second part, I will discuss how we envision to bridge scales between molecules and cells at the example of a cellular phenotype switch that requires a dynamic interplay between proteins and DNA. While single-molecule tools to probe the kinetics of biomolecules are well developed, similar approaches to study the dynamics of cellular processes such as gene expression are scarce. In the final part of my talk I will therefore present a new approach to tackle this problem using single-particle tracking
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    The Impact of DNA damages on Protein-DNA Interactions

    Date:
    05
    Tuesday
    April
    2022
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Ariel Afek
    Organizer: Department of Chemical and Structural Biology
    Contact: nicole.dorfman@weizmann.ac.il

    The multi-scale structure of chromatin in the nucleus

    Date:
    14
    Monday
    March
    2022
    Colloquium
    Time: 11:00-12:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Yuval Garini
    Organizer: Faculty of Chemistry
    Contact: sarah.amzallag@weizmann.ac.il
    Abstract: The DNA in a human cell which is ~2 meters long is packed in a ~10 μm radius nu ... Read more The DNA in a human cell which is ~2 meters long is packed in a ~10 μm radius nucleus. It is immersed in a condensed soup of proteins, RNA and enzymes and it is highly dynamic, while it must stay organized to prevent chromosome entanglement and for ensuring proper genome expression. Studying this nanometer – micrometer scale structure requires to use both high spatial and temporal resolutions and we combine comprehensive live-cell and molecular methods. I will discuss the latest findings on the chromatin organization, the role of lamin A that we found to be of major importance and the functionality of the structure, both for physical properties, and for its functionality on gene expression.
    Close abstract
    The multi-scale structure of chromatin in the nucleus Colloquium website

    Physics Hybrid Colloquium

    Date:
    10
    Thursday
    March
    2022
    Colloquium
    Time: 11:15-12:30
    Title: Phase Separation in Biological Cells: lessons from and for physics
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Prof. Samuel Safran
    Organizer: Faculty of Physics
    Contact: tamar.fuchs@weizmann.ac.il
    Abstract: Phase separation is generally a thermodynamic process in which a mixture reaches ... Read more Phase separation is generally a thermodynamic process in which a mixture reaches its lowest free energy state by self-assembling into meso- (or macro-) scale regions that are concentrated or dilute in a given molecular component. Familiar examples include the immiscibility of water and oil, the demixing of metal atoms in alloys, and the mesoscale formation of emulsions such as milk or paint. The fundamental physics behind both the equilibrium and non-equilibrium aspects of phase separation are well understood and this talk will begin with a brief review of those. A rapidly growing body of experiments suggests that phase separation is responsible for the formation of membraneless domains (also known as biomolecular condensates, with length scales on the order of microns) in biological cells. These compartments allow the cell to organize itself in space and can promote or inhibit biochemical reactions, provide regions in which macromolecular assemblies can form, or control the spatial organization of DNA (assembled with proteins as chromatin) in the cell nucleus. I will review some recent examples based on experiments done at the Weizmann Institute on phase separation of proteins and of chromatin in the nucleus and show how physics theory has led to their understanding. In the latter case, a new paradigm is emerging in which the genetic material is not necessarily uniformly distributed within the nucleus but separated into domains which in some cases, have a complex, “marshland”, mesoscale structure. But while many of the equilibrium aspects can be at least semi-quantitatively understood by extensions of statistical physics, biological systems often do not have constant overall compositions as is the case in the examples of oil-water, alloys and emulsions; for example, over time, the cell produces and degrades many proteins. The recent understanding of such strongly non-equilibrium effects has informed the theoretical physics of phase separation and has allowed us to establish a framework in which biological noise can be included. * Collaborations: Omar Arana-Adame, Gaurav Bajpai, Dan Deviri, Amit Kumar (Dept. Chemical and Biological Physics), group of Emmanuel Levy (Dept. Structural Biology) and group of Talila Volk (Dept. Molecular Genetics)
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    Application of new methods for DNA and proteins manipulation in the Structural Proteomics Unit

    Date:
    03
    Thursday
    March
    2022
    Lecture / Seminar
    Time: 09:00
    Location: via ZOOM
    Lecturer: Dr. Yoav Peleg
    Organizer: Department of Life Sciences Core Facilities
    Contact: Yoav.Peleg@weizmann.ac.il
    Gallery: Application of new methods for DNA and proteins manipulation in the Structural Proteomics Unit Gallery
    Application of new methods for DNA and proteins manipulation in the Structural Proteomics Unit Lecture / Seminar website

    Visualizing supercoiled DNA structure and interactions with base-pair resolution

    Date:
    15
    Tuesday
    February
    2022
    Lecture / Seminar
    Time: 14:00-15:00
    Location: https://weizmann.zoom.us/j/97858326006?pwd=RU0waUdtVHlFUUJjaERsNWZzd1RSdz09
    Lecturer: Dr. Alice L.B. Pyne
    Organizer: Department of Chemical and Structural Biology
    Contact: nicole.dorfman@weizmann.ac.il

    Student Seminar on Zoom - PhD Thesis Defense by Maya Amitai

    Date:
    19
    Wednesday
    January
    2022
    Lecture / Seminar
    Time: 10:00-11:00
    Lecturer: Maya Amitai, MD, PhD
    Organizer: Department of Brain Sciences
    Contact: naomi.moses@weizmann.ac.il
    Details: Student Seminar - PhD Thesis Defense Zoom link: https://weizmann.zoom.us/j/9109 ... Read more Student Seminar - PhD Thesis Defense Zoom link: https://weizmann.zoom.us/j/91093085114?pwd=RVBKbEZXbjlsaVZrUVRuNThtVHB1UT09 Meeting ID: 910 9308 5114 Password : 419366
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    Abstract: Depression and anxiety disorders are among the most common childhood psychiatric ... Read more Depression and anxiety disorders are among the most common childhood psychiatric disorders. Selective serotonin reuptake inhibitors (SSRIs) are generally considered first-line treatment for both depression and anxiety in this age group. However, 30%–40% of all patients who receive a sufficient dose and duration of treatment fail to respond. Moreover, SSRI use is frequently associated with adverse events (AEs), including activation symptoms, manic switch and increased suicidal behavior (SBs). These are particularly relevant in pediatric populations because of concerns about the suicide threat of SSRIs, resulting in a "black-box" warning. There are currently no biomarkers that can predict treatment response or AEs. Identification of such biomarkers could help to maximize the benefit-risk ratio for the use of SSRIs and speed the matching of treatment to patient. Given the fact that depression / anxiety risk is influenced by both genetic and environmental factors and that both state and trait factors will be important in treatment response prediction, a multidimensional biomarker panel covering several levels of biological information would likely be necessary. The main objective of this research thesis is to identify biomarkers that will aid in the prediction of response and suicidal and other AEs of SSRI treatment in children and adolescents treated for depression and/or anxiety disorders. We examined the involvement of specific biomarkers (miRNA’s, DNA methylation, single nucleotide polymorphism [SNP's] and metabolites) in the response to SSRIs treatment in children and adolescents and in the differences observed between individuals exhibiting response or non-response/AEs to treatment with SSRIs. Two hundred and sixty-six children and adolescents with depression and/or anxiety disorders were recruited and treated with fluoxetine. The overall response rate was 55%. Several targets from several biological domains (DNA methylation profile, miRNA’s and metabolites) were identifies as differentially expressed between responders and non-responders at baseline test. Pathway analysis of the predicted targets was carried out to assess their putative biological functions. Interestingly, when combining targets from the four biological domains, the targets were predicted to regulate specific biological pathways associated with immune system pathways and/or developmental pathways. Dysregulation of complex gene networks in the developing brain is thought to underlie depression with childhood or adolescent onset. Thus, the identified molecules might play critical roles in transcriptional networks related to treatment response and AEs. These transcriptional networks are particularly relevant to the developing human brain and to neurodevelopmental disorders with childhood/adolescent onset, such as depression and anxiety disorders. Zoom link: https://weizmann.zoom.us/j/91093085114?pwd=RVBKbEZXbjlsaVZrUVRuNThtVHB1UT09 Meeting ID: 910 9308 5114 Password : 419366
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