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Decoding the molecular mechanism of histone modification

Date:
31
Monday
March
2025
Colloquium
Time: 11:00-12:15
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Cynthia Wolberger
Organizer: Department of Chemical and Structural Biology
Contact: sarah.amzallag@weizmann.ac.il
Abstract: Post-translational modifications of histones play a central role in regulating a ... Read more Post-translational modifications of histones play a central role in regulating all cellular processes requiring access to DNA. Monoubiquitinated histone H2B-K120 is a hallmark of actively transcribed genes that plays multiple roles in activating transcription, while monoubiquitinated histone H2A-K119 is abundant in heterochromatin, which is transcriptionally silent. Our structural studies have revealed how histone H2B is specifically ubiquitinated and deubiquitinated, and ubiquitinated H2B stimulates histone methylation. We have also shown how ubiquitin can regulate access to the nucleosome acidic patch, a hotspot for interactions with other chromatin-modifying enzymes. I will also discuss recent studies of a histone kinase that has an unusual mode of binding nucleosomes.
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Decoding the molecular mechanism of histone modification Colloquium website

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    Exploring RNA and protein folding with Single-Molecule Force Spectroscopy

    Date:
    03
    Monday
    March
    2025
    Colloquium
    Time: 11:00-12:15
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Matthias Rief
    Abstract: Single-molecule force spectroscopy (SMFS) enables high-resolution insights into ... Read more Single-molecule force spectroscopy (SMFS) enables high-resolution insights into the kinetics and mechanisms of biomolecular interactions. In this talk, I will present how SMFS, helps uncover key principles in nucleic acid and protein folding. Examples discussed will include the microsecond invasion kinetics of toehold-mediated strand displacement (TMSD) of DNA and RNA as well as mRNA-Roquin interactions, which regulate mRNA degradation via specific 3’UTR hairpin structures. Finally, we study chaperone-mediated unfolding of the glucocorticoid receptor (GR), demonstrating how Hsp70/Hsp40 unfolds GR in discrete ATP-driven steps, stabilizing novel intermediates and acting as an unfoldase. These studies showcase SMFS as a powerful tool to resolve biomolecular dynamics providing new insights into RNA structure-function relationships and chaperone-mediated protein regulation.
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    Exploring RNA and protein folding with Single-Molecule Force Spectroscopy Colloquium website

    Programmable polymer materials empowered by DNA nanote

    Date:
    25
    Tuesday
    February
    2025
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Elisha Krieg
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Synthetic chemistry has enabled the creation of materials with remarkable proper ... Read more Synthetic chemistry has enabled the creation of materials with remarkable properties, yet they often lack thedynamic nature exhibited by biological systems. In contrast, living matter is self-organizing and responsive, whichis critical for processes such as cell differentiation, sensing, transport, actuation, structural support, and—morebroadly—adaptation to internal and external stimuli. Intriguingly, the application of DNA nanotechnology tosynthetic materials has opened avenues for achieving a range of features and a level of control reminiscent ofbiological systems. These materials have begun to emulate key cellular mechanisms, including the modulation ofviscoelastic properties in the extracellular matrix, cytoskeletal shape changes, control of molecular transport, andthe localization of processes in biomolecular condensates. In this talk, I will describe our progress in developingsuch programmable materials and highlight two recent examples. First, I will introduce a novel precision matrix forculturing cells and organoids. By integrating customizable mechanics with predictable, responsive features, thismatrix both guides and probes cellular development. Second, I will present an exotic form of soft matter that isself-assembled from more than 16,000 unique molecular components. This material demonstrates that highcompositional complexity can yield unique molecular architectures with emergent properties distinct from thoseof conventional polymers.References:* Speed et al. J. Polym. Sci. 2023, 61, 1713.* Peng et al., Nature Nanotech. 2023, 18, 1463.* Krieg & Shih, Angew. Chem. Int. Ed. 2018, 57, 714.* Gupta & Krieg, Nucl. Acids Res. 2024, 52, e80.* Prakash et al., Nature Nanotech. 2021, 16, 2021.* Speed et al., BioRxiv 2024. https://doi.org/10.1101/2024.07.12.603212
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    The Clore Center for Biological Physics

    Date:
    23
    Sunday
    February
    2025
    Lecture / Seminar
    Time: 13:15-14:30
    Title: What can microbes tell us about their environment
    Location: Nella and Leon Benoziyo Physics Library
    Lecturer: Dr. David Zeevi
    Contact: debbie.hen@weizmann.ac.il
    Abstract: Microbial communities act as living sensors of their environment, continuously a ... Read more Microbial communities act as living sensors of their environment, continuously adapting to and recording changes in their surroundings across temporal and spatial scales. This capacity, combined with their central role in global biogeochemical cycles, makes microbes ideal indicators of ecosystem health. However, our understanding of how these communities respond to anthropogenic perturbations remains limited. In this talk, I will present two complementary approaches to decode environmental information from microbial communities. First, I will show that environmental temperature can be accurately predicted from microbial DNA composition alone, revealing fundamental principles of genome-wide thermal adaptation that transcend ecosystem boundaries. This work uncovers how evolutionary pressures shape microbial genomes across diverse habitats and provides insights into long-term community responses to climate change. Second, I will introduce a novel approach for measuring real-time bacterial growth rates in natural environments from a single sample, without prior knowledge on community composition. This method could enable us to track immediate ecological responses to environmental perturbations. By combining these evolutionary and ecological perspectives, we can begin to establish universal principles governing microbial responses to environmental change across different timescales. This multi-scale understanding is crucial for predicting and potentially mitigating the impacts of human activities on microbial ecosystems, from soil degradation to climate change.FOR THE LATEST UPDATES AND CONTENT ON SOFT MATTER AND BIOLOGICAL PHYSICS AT THE WEIZMANN, VISIT OUR WEBSITE: https://www.biosoftweizmann.com/
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    From chromosomes to single genes: Designing DNA molecules for autonomous cell-free systems

    Date:
    04
    Tuesday
    February
    2025
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Ferdinand Greiss
    Organizer: Department of Chemical and Structural Biology

    The Clore Center for Biological Physics

    Date:
    02
    Sunday
    February
    2025
    Lecture / Seminar
    Time: 12:45-14:30
    Title: Design principles of protein-DNA Recognition Specificity in Embryonic Stem Cells
    Location: Nella and Leon Benoziyo Physics Building
    Lecturer: David B. Lukatsky
    Organizer: Clore Center for Biological Physics
    Contact: debbie.hen@weizmann.ac.il
    Abstract: Transcription factors (TFs) bind genomic DNA regulating gene expression and deve ... Read more Transcription factors (TFs) bind genomic DNA regulating gene expression and developmental programs in embryonic stem cells (ESCs). Even though comprehensive genome-wide molecular maps for TF-DNA binding are experimentally available for key pluripotency-associated TFs, the understanding of molecular design principles responsible for TF-DNA recognition remains incomplete. In this talk, I will show that binding preferences of key pluripotency TFs exhibit bimodality in the local GC-content distribution. Sequence-dependent binding specificity of these TFs is distributed across three major contributions. First, local GCcontent is dominant in high-GC-content regions. Second, recognition of specific k-mers is predominant in low-GC-content regions. Third, short tandem repeats (STRs) are highly predictive in both low- and high-GC-content regions. In sharp contrast, binding preferences of a key oncogenic protein, c-Myc, are exclusively dominated by local GC-content and STRs in high-GC-content genomic regions. I will propose that the transition in the TF-DNA binding landscape upon ESC differentiation is solely regulated by the concentration of c-Myc, which forms a bivalent c-Myc-Max heterotetramer upon promoter binding, competing with key pluripotency factors. Taken together, these findings point out that c-Myc may significantly affect the genome-wide TF-DNA binding landscape, chromatin structure, and enhancerpromoter interactions.FOR THE LATEST UPDATES AND CONTENT ON SOFT MATTER AND BIOLOGICAL PHYSICS AT THE WEIZMANN, VISIT OUR WEBSITE: https://www.biosoftweizmann.com/
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    Integrating Peptides and DNA for Tailored Material Design

    Date:
    27
    Monday
    January
    2025
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Schmidt Lecture Hall
    Lecturer: Dr. Zohar A. Arnon
    Organizer: Department of Molecular Chemistry and Materials Science
    Contact: natali.levin@weizmann.ac.il
    Abstract: In nature, sequence-specific biopolymers, such as peptides and nucleic acids, ar ... Read more In nature, sequence-specific biopolymers, such as peptides and nucleic acids, are essential to various biological systems and processes. These biopolymers are utilized in materials science to achieve precise property control. Typically, variations in amino acid sequences focus on functional regulation while nucleotides are used for structural control. This raises the question: How can we integrate peptide-based functionality with the spatial precision of DNA nanotechnology for innovative material design? Here, I will present examples illustrating the incredible properties of peptide self-assembly from my PhD, and the remarkable nanoarchitecture design achieved through DNA nanotechnology from my Postdoc. These two key elements establish a vision of utilizing and synergizing peptide functionality with structural control achieved by DNA nanotechnology.Specifically, I will show how subtle changes in the molecular environment influence the morphology and behavior of peptide assemblies such as diphenylalanine crystals and enable control over their growth and disassembly processes, revealing insights into peptide-based material manipulation (Nat. Commun., 2016). Another example is that of the amorphous assemblies of tri-tyrosine peptides, where we linked the molecular arrangement to unique mechanical and optical properties of glass-like peptide structures (Nature, 2024).Next, I will introduce the principles of DNA nanotechnology for advanced structural control. By designing DNA nano-frames capable of self-assembling into organized lattices, we created micron-scale 3D materials. We discovered that a minor modification in DNA linker length induces a crystalline phase transition, from simple cubic to face-centered cubic structures, altering lattice geometry. In addition, we established a method using acoustic waves to achieve scalable and morphologically controllable DNA assemblies at the millimetric scale (Nat. Commun., 2024). This approach highlights how DNA nanotechnology provides unparalleled spatial control, decoupling structural architecture from functional elements such as peptides and nanoparticles. Together, these projects illustrate how peptides and DNA nanotechnology can be potentially integrated to engineer novel materials and enhance our capacity to design materials with tailored properties across scales.
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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.
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    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