Upcoming

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Advanced Practical Workshop in Drug Discovery

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

    Past

    All Events

    G-INCPM-Special Seminar - Prof. Govert Somsen, Division of BioAnalytical Chemistry, Vrije University, Amsterdam - "Probing the heterogeneity of intact proteins"

    Date:
    18
    Wednesday
    September
    2019
    Lecture / Seminar
    Time: 15:00-16:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Govert Somsen
    Organizer: Department of Life Sciences Core Facilities
    Abstract: Emerging requirements in biopharmaceutical quality control and top-down proteomi ...Emerging requirements in biopharmaceutical quality control and top-down proteomics, have led to a growing interest in intact protein analysis. Detailed characterization of intact protein heterogeneity, e.g. resulting from post-translational modifications, is a challenging task. Separation prior to mass spectrometric (MS) detection commonly is essential to achieve reliable and sensitive assignment of intact protein variants. Conventional liquid chromatographic (LC) protein separation methods often show poor compatibility with MS and/or lack the selectivity to resolve proteoforms. Moreover, LC conditions may be denaturing, precluding assessment of protein conformers and proteoform affinity. This lecture presents the design and application of new LC-MS and capillary electrophoresis (CE)-MS methods allowing detailed determination of the heterogeneity of intact proteins. Performance will be illustrated by characterization of pharmaceutical proteins, such as interferon-beta, erythropoietin, and monoclonal antibodies (mAbs), as well as cell-lysate proteins and IgGs in human plasma.

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

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

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

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

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

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

    Brain control and readout at biologically relevant resolutions

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

    Departmental Seminar

    Date:
    12
    Sunday
    May
    2019
    Lecture / Seminar
    Time: 13:00-14:00
    Title: Deciphering Stress-granules disassembly by proximity proteomics
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Hagai Marmor
    Organizer: Department of Molecular Genetics

    Next Generation Personalized Proteomics Driving Biomarker Discovery and Precision Medicine

    Date:
    06
    Monday
    May
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Towia Libermann
    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

    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.

    Imm Special Guest Seminar:Prof. Jo Van Ginderachter, will lecture on "Macrophages in the healthy and the tumor-bearing brain: linking single-cell transcriptomics to function."

    Date:
    16
    Tuesday
    April
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Jo Van Ginderachter
    Organizer: Department of Immunology

    Genetics, HSP expressomics and proteomics to understand how plants feel the heat and meet the challenges of global warming

    Date:
    15
    Monday
    April
    2019
    Lecture / Seminar
    Time: 14:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Pierre Goloubinoff
    Organizer: Department of Plant and Environmental Sciences
    Details: Host: Prof. Meir Edelman

    Toward a high-fidelity artificial retina

    Date:
    02
    Tuesday
    April
    2019
    Lecture / Seminar
    Time: 14:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. E. J. Chichilnisky
    Organizer: Department of Neurobiology
    Details: Host: Prof. Elad Schneidman elad.schneidman@weizmann.ac.il tel: 2239 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: Retinal prostheses represent an exciting development in science, engineering, an ...Retinal prostheses represent an exciting development in science, engineering, and medicine – an opportunity to exploit our knowledge of neural circuitry and function to restore or even enhance vision. However, although existing retinal prostheses demonstrate proof of principle in treating incurable blindness, they produce limited visual function. Some of the reasons for this can be understood based on the exquisitely precise and specific neural circuitry that mediates visual signaling in the retina. Consideration of this circuitry suggests that future devices may need to operate at single-cell, single-spike resolution in order to mediate naturalistic visual function. I will show large-scale multi-electrode recording and stimulation data from the primate retina indicating that, in some cases, such resolution is possible. I will also discuss cases in which it fails, and propose that we can improve artificial vision in such conditions by incorporating our knowledge of the visual system in bi-directional devices that adapt to the host neural circuity. Finally, I will briefly discuss the potential implications for other neural interfaces of the future.

    Mass Spectrometry Based Proteomics: state of the art

    Date:
    07
    Thursday
    March
    2019
    Lecture / Seminar
    Time: 09:00-10:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Yishai Levin
    Organizer: Department of Life Sciences Core Facilities

    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.

    Sequencing giants - the wild emmer wheat genome assembly

    Date:
    05
    Tuesday
    February
    2019
    Lecture / Seminar
    Time: 11:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Raz Avni
    Organizer: Department of Plant and Environmental Sciences
    Details: Host:Dr. Einat Segev

    Proteomics and metabolomics from ancient documents

    Date:
    24
    Thursday
    January
    2019
    Lecture / Seminar
    Time: 13:00
    Location: Helen and Martin Kimmel Center for Archaeological Science
    Lecturer: Dr. Gleb Zilberstein
    Organizer: Academic Educational Research

    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

    From single-cell variability and correlations across lineages to the population growth

    Date:
    13
    Thursday
    December
    2018
    Colloquium
    Time: 11:15-12:30
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Ariel Amir
    Organizer: Faculty of Physics
    Details: 11:00 – coffee, tea, and more
    Abstract: Genetically identical microbial cells often display diverse phenotypes. Stochast ...Genetically identical microbial cells often display diverse phenotypes. Stochasticity at the single-cell level contributes significantly to this phenotypic variability, and cells utilize a variety of mechanisms to regulate noise. In turn, these control mechanisms lead to correlations in various cellular traits across the lineage tree. I will present recent models we developed for understanding cellular homeostasis, with special focus on protein levels and cell size. These models allow us to characterize single-cell variability, including the emerging correlations and distributions. I will discuss the implications of stochasticity on the population growth. In contrast to the dogma, we find that variability may be detrimental to the population growth, suggesting that evolution would tend to suppress it.

    Advances in Drug Discovery

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

    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.

    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

    G-INCPM Science Meeting - Dr. David Morgenstern & Rotem Barzilay - "RawBeans"

    Date:
    14
    Wednesday
    November
    2018
    Lecture / Seminar
    Time: 14:30-15:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. David Morgenstern & Rotem Barzilay - G-INCPM
    Organizer: Department of Biomolecular Sciences
    Abstract: RawBeans" ...RawBeans"

    G-INCPM - Special Seminar - Prof. Ofer Feinerman, Dept. of Physics of Complex Systems, Weizmann - "Managing information over multiple organizational scales"

    Date:
    31
    Wednesday
    October
    2018
    Lecture / Seminar
    Time: 11:00-12:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Organizer: Life Sciences
    Abstract: A main adaptive advantage of social insects is their ability to concurrently pro ...A main adaptive advantage of social insects is their ability to concurrently probe multiple locations while gathering information over scales that are much larger than that of a single individual. Collecting information is, however, only the first step since information fragments must be fused to yield collective action. This information aggregation process is far from trivial and can teach us about the tensions between individual and group and how these might be resolved in an effective manner. This talk will discuss several examples for such tensions and their resolution in the context of cooperative transport by longhorn crazy ants: collectively accumulated information vs. updated individual information, large scale information required for effective action vs. small scale information available to individuals, and group level consensus from conflicting individual information. All these examples point towards information collection and aggregation schemes that utilize the advantages of large groups without compromising the valuable information gathered by each individual.

    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.

    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.

    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.

    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.

    G-INCPM - Special Seminar - Prof. Asaph Aharoni, Dept. of Plant & Environmental Sciences, Faculty of Biochemistry, Weizmann - "The Plant Metabolome in Action"

    Date:
    13
    Wednesday
    June
    2018
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Asaph Aharoni
    Organizer: Department of Biomolecular Sciences
    Abstract: The regulation of metabolic pathways in plants is constantly tuned in order to s ...The regulation of metabolic pathways in plants is constantly tuned in order to suit the needs of development and fitness. Our main research objective is to unravel networks of genes and proteins which coordinate the activity of metabolic pathways, predominantly secondary metabolism, during plant development and stress response. An integrated investigation of several members of the Solanacea family rather than studying a single plant, provided us with unprecedented insights to metabolic biology in these species. Most if not all processes characterized, impact to a certain degree key quality, nutritional and post-harvest traits of these crop plants. Integrating cutting-edge transcriptomics, proteomics and metabolomics tools together with genes co-expression assays were of great value in making several key discoveries. In a recent example, combined co-expression analysis and metabolic profiling in tomato and potato led to the discovery of the multi-step, core pathway leading to the formation of the renowned Solanum alkaloids including the biosynthesis of their precursor, cholesterol. This class of molecules represent important anti-nutritional compounds in these crop plants. In the presentation, I will highlight several advanced technologies and genetic research tools and the invaluable knowledge on core metabolic traits obtained through combining them in a single study.

    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

    LECTURE IN HEBREW - G-INCPM - Special Seminar - Prof. Shimon Reisner, Head of Midgam - "Politics, Economics and the Health System"

    Date:
    22
    Tuesday
    May
    2018
    Lecture / Seminar
    Time: 11:00-12:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Shimon Reisner, Head of Midgam
    Organizer: Department of Biomolecular Sciences

    G-INCPM Special Seminar - Dr. Daniel Liber, Business Development Manager, Automation, Takara Bio Europe - "SMARTer ICELL8: The Open Platform for Single-Cell Genomics"

    Date:
    01
    Tuesday
    May
    2018
    Lecture / Seminar
    Time: 14:30-15:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Organizer: Department of Biomolecular Sciences
    Abstract: Single-cell genomics allows to understand cellular heterogeneity at an unprecede ...Single-cell genomics allows to understand cellular heterogeneity at an unprecedented resolution. The SMARTer ICELL8 Single-Cell System gives more control in the experimental design, more confidence in the data and unique workflow flexibilities while reducing the experimental costs. The ICELL8 multi-nanowell chip can isolate hundreds of cells from multiple samples at once, from the very small, like nuclei from frozen tissues, to the very large, like primary cardiomyocytes and spheroids. The SMARTer ICELL8 has been validated for multiple applications, including gene expression analysis, full-length transcriptomics, T-Cell Receptor sequencing and ATAC-seq, which have been developed by Takara Bio’s R&D or ICELL8 users.

    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.

    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

    G-INCPM 5 Year Anniversary Workshop

    Date:
    25
    Sunday
    March
    2018
    Conference
    Time: 08:00-17:00
    Location: David Lopatie Conference Centre
    Organizer: G-INCPM

    “Mass spectrometry based proteomics: state of the art”

    Date:
    20
    Tuesday
    March
    2018
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Dr.Yishai Levin
    Organizer: Department of Structural Biology

    Special Seminar: "Single molecule, real-time (SMRT) sequencing - advanced genomics with long read sequencing"

    Date:
    15
    Thursday
    March
    2018
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Swati Ranade
    Organizer: Department of Life Sciences Core Facilities

    G-INCPM-Special Seminar - Dr. Shalev Itzkovitz, Dept. of Molecular Cell Biology, Weizmann - "Spatial Transcriptomics of Mammalian Tissues"

    Date:
    14
    Wednesday
    March
    2018
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Dr. Shalev Itzkovitz
    Organizer: Department of Biomolecular Sciences
    Abstract: Mammalian tissues are often composed of repeating anatomical units that are pola ...Mammalian tissues are often composed of repeating anatomical units that are polarised by morphogens or directional blood flow. Thus single cells at different tissue coordinates operate in distinct microenvironment. This spatial diversity enables optimisation of tissue function by allocating different tasks to cells that reside in distinct tissue locations. To explore this spatial division of labor on a genome-wide scale we are combining single cell transcriptomics with in-situ measurements in intact tissues to enable inference of the sequenced cells’ original tissue locations. This approach enables reconstructing global spatial gene expression atlases. I will demonstrate these approaches on two stereotypical and highly structured organs - the liver and the intestinal epithelium.

    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.

    "Tutorial lecture on cross-linking MS (XL-MS)"

    Date:
    16
    Tuesday
    January
    2018
    Lecture / Seminar
    Time: 10:30-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. David Morgenstern
    Organizer: Department of Biomolecular Sciences
    Abstract: Mass spectrometry based proteomics became an enabling technology in the investig ...Mass spectrometry based proteomics became an enabling technology in the investigation of proteins and proteomes – from protein dynamics, through signaling, protein network interaction to structural determination. The combination of chemical crosslinking of proteins with mass spectrometry (XL-MS) opened up an opportunity to investigate protein-protein interactions within the framework of a whole proteome, even in-vivo, as well as provide a powerful tool for structure determination of proteins and protein complexes. In recent years, improvement in instrumentation and computing power led to improved accessibility of this technique to the non-expert researcher. However, XL-MS suffers from basic deficiencies due to intrinsic issues with sample preparation, data acquisition and analysis. In this tutorial we will discuss current hardware and software capabilities and limitations, and how experiment design can best utilize current capabilities for a successful experiment

    G-INCPM Special Seminar - Dr. Yifat Merbl, Dept. of Immunology, Weizmann - "A Ubiquitin-Dependent Mechanism of Proteostasis Control"

    Date:
    03
    Wednesday
    January
    2018
    Lecture / Seminar
    Time: 14:00-15:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Dr. Yifat Merbl
    Organizer: Department of Biomolecular Sciences
    Abstract: Primary focus has been given to the endoplasmic reticulum (ER) in the context of ...Primary focus has been given to the endoplasmic reticulum (ER) in the context of quality control of misfolded or aberrant proteins. Although passage from the ER through the Golgi is mandatory for endomembrane and secreted proteins, the Golgi has mainly been studied in the context of its role as a packaging and sorting organelle, and as a site of protein glycomodification. Here I will describe the discovery of a Golgi ApparatusRelated Degradation (GARD) quality control mechanism, which constitutes a novel and important checkpoint in the secretory pathway. Our findings may have significant implications on proteostasis regulation in health and disease.

    Activity-based proteomics – protein and ligand discovery on a global scale

    Date:
    05
    Tuesday
    December
    2017
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Benjamin F. Cravatt
    Organizer: Department of Biomolecular Sciences
    Abstract: Genome sequencing projects have revealed that eukaryotic and prokaryotic organis ...Genome sequencing projects have revealed that eukaryotic and prokaryotic organisms universally possess a huge number of uncharacterized proteins. The functional annotation of these proteins should enrich our knowledge of the biochemical pathways that support human physiology and disease, as well as lead to the discovery of new therapeutic targets. To address these problems, we have introduced chemical proteomic technologies that globally profile the functional state of proteins in native biological systems. Prominent among these methods is activity-based protein profiling (ABPP), which utilizes chemical probes to map the activity state of large numbers of proteins in parallel. In this lecture, I will describe the application of ABPP to discover and functionally annotate proteins in mammalian physiology and disease. I will also discuss the generation and implementation of advanced ABPP platforms for proteome-wide ligand discovery.

    G-INCPM Special Seminar - Dr. Tamar Paz-Elizur, Dept. of Biomolecular Sciences, Weizmann - "Translating DNA repair for the battle against lung cancer"

    Date:
    04
    Monday
    December
    2017
    Lecture / Seminar
    Time: 11:00-12:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Dr. Tamar Paz
    Organizer: Department of Biomolecular Sciences
    Abstract: DNA repair is a key mechanism for eliminating DNA damage and preventing mutation ...DNA repair is a key mechanism for eliminating DNA damage and preventing mutations, and is therefore a major natural defense mechanism against cancer. With the goal of exploring the role of DNA repair in sporadic cancer we have developed a panel of functional DNA repair assays, highly reproducible and robust, that enable us to measure the activity of specific DNA repair enzymes directed towards oxidative lesions. In my talk, I will describe the results of two epidemiological/clinical blinded case-control studies, conducted in Israel and in the UK, showing that lung cancer patients have imbalanced DNA repair capacity compare to healthy people. The potential use of these DNA repair biomarkers in lung cancer prevention, early detection & therapy will be discussed.

    Bridging between personalized medicine and T-cell based immunotherapy

    Date:
    20
    Monday
    November
    2017
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Special Guest Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Cyrille Cohen
    Organizer: Department of Biological Regulation

    G-INCPM Special Seminar - Prof. Amnon Peled, CEO-CSO, Biokine Therapeutics Ltd., Ness-Ziona - "Development of HTS for Novel Chemokine Antagonists"

    Date:
    15
    Wednesday
    November
    2017
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Amnon Peled
    Organizer: Department of Biomolecular Sciences
    Abstract: Chemokines and their receptors play critical roles in the progression of autoimm ...Chemokines and their receptors play critical roles in the progression of autoimmunity and inflammation and cancer. Typically, multiple chemokines are involved in the development of these pathologies. Indeed, targeting single chemokines or chemokine receptors has failed to achieve significant clinical benefits in treating autoimmunity and inflammation. In our work, promiscuous chemokine binding peptides that could bind and inhibit multiple inflammatory chemokines, such as CCL20, CCL2, CCL5, and CXCL9/10/11, were selected from phage display libraries. These peptides were cloned into human mutated immunoglobulin Fc-protein fusions (peptibodies). These peptibodies showed a significant inhibition of disease progression in a variety of animal models for autoimmunity, inflammation and cancer. Based on our peptibodies we develop HTP screening system which allow us the identification of novel anti chemokines small molecules.

    New adventures with Nanopore sequencing

    Date:
    01
    Wednesday
    November
    2017
    Lecture / Seminar
    Time: 09:15-11:30
    Title: Our goal: to enable the analysis of any living thing, by any person, in any environment
    Location: Max and Lillian Candiotty Building
    Lecturer: Jackie Evans
    Organizer: Department of Life Sciences Core Facilities
    Abstract: Oxford Nanopore Technologies aims to disrupt the paradigm of biological analysis ...Oxford Nanopore Technologies aims to disrupt the paradigm of biological analysis. Our technology and commercial model has already opened up DNA analysis to researchers who previously had no direct access to sequencing technologies, freeing them up to perform analyses in their own labs or in the field, and in real time. We continually improve the technology performance, make it easier to use and expand the ways in which users can access nanopore sequencing. This technology pathway is designed to enable the analysis of any living thing, by any person, in any environment. This seminar will introduce the world's first and only nanopore DNA sequencer, the MinION which is able to sequence DNA and RNA directly, without the need for PCR. It will include examples of the MinION’s portability, the opportunities that come from real-time analysis and how long reads meet some of the challenges that exist in genomic research today. It will show how this low-cost device that has been designed to bring easy biological analyses to anyone, whether in scientific research, education or a range of real-world applications such as disease/pathogen surveillance or even microgravity biology. The MinION is in use by a thriving community of scientists in more than 70 countries, where it is enabling a myriad applications within the traditional laboratory environment and in the field. Nanopore sequencing is full scalable through the GridION X5 and PromethION which can be used to address sequencing projects of any size. Both these systems have flow cells that can be used independently or altogether for larger projects or anything in between. Large and small projects can be run at the same time, started at different times and run for as long as necessary to generate the data required. Join us to learn: • How nanopore sequencing works • What makes it different • The options for DNA and RNA sequencing • How easy it is to scale experiments • What’s involved in starting to use the technology

    IMM Guest Seminar: Prof. Smita Krishnaswamy, from Yale school of Medicine, will lecture on "Manifold-Learning Frameworks for Extracting Structure from High-throughput Single-Cell Datasets", Monday Oct 23rd, 2017

    Date:
    23
    Monday
    October
    2017
    Lecture / Seminar
    Time: 10:00
    Location: Wolfson Building for Biological Research
    Lecturer: Prof. Smita Krishnaswamy
    Organizer: Department of Immunology
    Abstract: Recent advances in single-cell technologies enable deep insights into cellular d ...Recent advances in single-cell technologies enable deep insights into cellular development, gene regulation, and phenotypic diversity by measuring gene expression and epigenetics for thousands of single cells in a single experiment. While these technologies hold great potential for improving our understanding of cellular states and progression, they also pose new challenges in terms of scale, complexity, noise and measurement artifact which require advanced mathematical and algorithmic tools to extract underlying biological signals. In this talk, I cover one of most promising techniques to tackle these problems: manifold learning, and the related manifold assumption in data analysis. Manifold learning provides a powerful structure for algorithmic approaches to naturally process and the data, visualize the data and understand progressions as well as to find phenotypic diversity as well and infer patterns in it. I will cover two alternative approaches to manifold learning, diffusion-based and deep learning-based and show results in several projects including:1) MAGIC (Markov Affinity-based Graph Imputation of Cells): an algorithm for denoising and transcript recover of single cells applied to single-cell RNA sequencing data from the epithelial-to-mesenchymal transition in breast cancer, 2) PHATE (Potential of Heat-diffusion Affinity-based Transition Embedding): a visualization technique that offers an alternative to tSNE in that it emphasizes progressions and branching structures rather than cluster separations shown on several datasets including a newly generated embryoid body differentiation dataset, and 3) SAUCIE (Sparse AutoEncoders for Clustering Imputation and Embedding): a novel auto encoder architecture that performs denoising, batch normalization, clustering and visualization simultaneously for massive single-cell data sets from multi-patient cohorts shown on mass cytometry data from Dengue patients.

    G-INCPM Special Seminar - Prof. Izhak Haviv, Cancer Personalized Medicine & Genomic Diagnostics Lab, Azrieli Faculty of Medicine, Zfat, Bar-Ilan University - "Evidence-based, personalized, or immuno-medicine – where’s the perfect healthcare"

    Date:
    15
    Sunday
    October
    2017
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Izhak Haviv
    Organizer: Department of Biomolecular Sciences
    Abstract: The etiological bases of cancer are a large number of ‘bugs’, mutations in t ...The etiological bases of cancer are a large number of ‘bugs’, mutations in the human genome, mostly accumulating in somatic cells during patient’s lifespan. It took more than a century to translate this etiological insight into new ways to smart-bomb the cancer away. As new treatment options emerge, healthcare guidelines seek ways, such companion testing, to identify the patient, the treatment is most likely to benefit. The dynamic nature of the field of medical discoveries poses a challenge to the clinical decision making process, and guidelines have therefore gone through a series of paradigm shifts, all based on risk-benefit assessments. First, in the evidence-based paradigm, optional treatments are ranked according to the fraction of patients the treatment is likely to benefit, starting from the most commonly useful treatment and down the fractional benefit rank. Then, personalized medicine approach utilizes clinical and genomic sequence and molecular analyses, to rearrange the treatments rank, and recommend each patient with their own best treatment. In the most recent paradigm, immune-oncology, we profile the direct adaptive immune reaction, T-cell receptor sequence, to cancer-borne somatic mutations. The unique sequence of the respective T-cell receptors had been demonstrated to genetically code for the recognition and elimination of cells, carrying and presenting the mutant sequence. In other words, the cure to each patient is hidden in their own body, and once discovered, has the potential to harness the progression of cancer, as is being done for patients with high mutation load and immunological checkpoint inhibitors. While this approach is more bioinformatically and experimentally intensive, the results obtained from this approach are far superior, both in the end-stage patients it succeeds to benefit, as well as the duration of remission. Using double-autologous patient-derived xenografts, that model both the cancer tissue, as well as the immune system of each patient, we are harnessing these technologies to improve and accelerate the implementation of those new paradigms in the clinical practice.

    G-INCPM Special Seminar - Prof. Yuval Ebenstein, Dept. of Chemical Physics, School of Chemistry, Tel-Aviv Univ. - "Beyond NGS - Single-Molecule Genomics"

    Date:
    03
    Tuesday
    October
    2017
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Yuval Ebenstein
    Organizer: Department of Biomolecular Sciences
    Abstract: Next generation sequencing (NGS) is revolutionizing all fields of biological res ...Next generation sequencing (NGS) is revolutionizing all fields of biological research but it fails to extract the full range of information associated with genetic material. Complementary genomic technologies that analyze individual, unamplified genomic DNA are filling the gaps in the capabilities of NGS. Using such technologies we gain access to the structural variation and long range patterns of genetic and epigenetic information. Recent results from our lab demonstrate our ability to detect and map the epigenetic marks 5-methylacytosine and 5-hydroxymethylcytosine as well as various forms of DNA damage on individual genomic DNA molecules. This new technology allows genetic and epigenetic variation calling on the single cell level without the need to process single cells.

    G-INCPM Special Seminar - Prof. Tamar Flash, Dept. of Computer Science & Applied Mathematics, Weizmann Institute - "Principles and strategies in the control of human movement: behavioral, modeling and brain imaging studies"

    Date:
    13
    Wednesday
    September
    2017
    Lecture / Seminar
    Time: 11:00-12:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Tamar Flash
    Organizer: Life Sciences
    Abstract: In my talk I will discuss several recent research directions that we have taken ...In my talk I will discuss several recent research directions that we have taken to explore the different principles underlying the construction and control of complex human upper arm and gait movements. In these studies we combine experimental recordings of human movements with the development of mathematical models aiming at providing rigorous quantitative descriptions of human movement and investigating the underlying neural control strategies. One important topic I will focus on is motor compositionality, exploring the nature of the motor primitives underlying the construction of complex movements at different levels of the motor hierarchy and the topic of motor coordination and the mapping between different control levels. The second topic I will focus on is motion kinematics and timing, describing a series of behavioral and brain imaging studies demonstrating the strong coupling between motion production and perception. Finally, I will illustrate the application of the new gained understanding in studies of different neurological movement disorders.

    G-INCPM Special Seminar - Prof. Abraham Shanzer, The Dept. of Organic Chemistry, Weizmann Institute - "Biomimetic Chemistry: Mimicking Biological Diversity & Addressing Technological Challenges"

    Date:
    26
    Wednesday
    July
    2017
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Abraham Shanzer
    Organizer: Department of Biomolecular Sciences
    Abstract: ‘Biomimetic Chemistry’ presents a conceptual approach to the art of model bu ...‘Biomimetic Chemistry’ presents a conceptual approach to the art of model building attempting to imitate the activity of a biological system by emphasis on the function of a substrate rather than on its detailed molecular structure. In the talk today I will center on the approach, governing the fundamental phenomenon of molecular recognition. The end goal is to formulate a set of rules essential to the design of molecules matching a specific biological system. Microbial iron-carriers, Siderophores, provide a useful platform for studying these principles. Several series of ferrichrome biomimetic analogs varying in length and polarity of the chains separating between the tripodal scaffold and the pendent FeIII chelating hydroxamic acid groups were prepared and studied. Microbial growth promotion was conducted on bacteria (E. coli, and P. putida) and fungi (U. maydis). These studies show a wide range of siderophore activity: from a rare case of species-specific growth promotor in P. putida to an analog with broad-spectrum activity matching ferrichrome in cross-phylum activity and uptake pathway. A fluorescent conjugate, to the broad-rang analog, provide clear images of the iron-free siderophore final destination in bacteria (periplasmic space) vs fungi (cytosol) mapping distinctly new therapeutic targets. Quantum Dots (QD) decorated with the most potent ferrichrome (FC) analog provided a tool for immobilization of FC-recognizing bacteria. Bacterial clusters formed around QDs, provide a platform for their selection and concentration. The fascinating field of lanthanide-clusters will be introduces and their unique properties describe, possible future opportunities and application will be discussed.

    Deciphering the wastewater resistome and its potential impact on downstream environments

    Date:
    04
    Sunday
    June
    2017
    Lecture / Seminar
    Time: 11:00
    Location: Sussman Family Building for Environmental Sciences
    Lecturer: Eddie Cytryn, PhD
    Organizer: Department of Earth and Planetary Sciences
    Abstract: Wastewater treatment plants consolidate high loads of fecal and environmental ba ...Wastewater treatment plants consolidate high loads of fecal and environmental bacteria and residual concentrations of antibiotics and consequentially, effluents released from these facilities may contribute to antibiotic resistance in downstream ecosystems. This is especially relevant in arid and semi-arid environments, where treated wastewater (TWW) is used for irrigation. The goal of this study was to pinpoint key antibiotic resistance genes (ARGs) in wastewater effluents and to determine the impact of TWW irrigation on antibiotic resistance in terrestrial and food-associated microbiomes. The diversity and abundance of ARGs was evaluated in wastewater effluents, in TWW -irrigated soils and in crops irrigated with TWW using state of the art molecular, genomic and bioinformatic analyses. Three specific methods were applied: (A) a novel high-throughput amplicon sequencing methodology that specifically targeted ARGs associated with integron gene cassettes in effluents from 12 wastewater treatment facilities across Europe and in pristine vs. wastewater effluent-saturated soil; (B) quantitative PCR that assessed the abundance of selected ARGs along freshwater- and TWW-irrigated, water-soil-crop continuum; and (C) comparative in-silico-based analyses of human gut, wastewater and soil metagenomes to determine specific associations between wastewater and soil resistomes. Our results reveal that wastewater effluents contain a diverse array of ARGs, and that specific ARGs and class 1 integrons (mobile genetic elements that often harbor ARGs) are profuse and strongly associated with wastewater effluents. In contrast we found that other ARGs that are ubiquitous to soil regardless of TWW irrigation suggesting that these elements are common in environmental microbiomes. Collectively, the study indicates the distribution of ARGs in the environment is highly complex and is impacted by both natural and anthropogenic factors, and that while the impact of wastewater-derived ARGs in TWW-irrigated soils is limited, there is evidence that plasmid- and integron-associated ARGs are disseminated to soil microbiomes.

    Cellular heterogeneity and maturation in the mouse brain revealed by single-cell transcriptomics

    Date:
    21
    Sunday
    May
    2017
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Amit Zeisel
    Organizer: Department of Biological Regulation
    Abstract: The mammalian central nervous system is arguably the most complex system studied ...The mammalian central nervous system is arguably the most complex system studied in biology. Normal function of the brain relies on the assembly of a diverse set of cell-types, including most prominently neurons, but also glial cells and vasculature. We developed and applied large-scale single-cell RNA sequencing for unbiased molecular cell-type classification in various regions of the mouse brain. First, I will describe our initial work on the cortex and hippocampus, and later give two examples where we dissect the maturation process of (I) cells from the oligodendrocyte lineage across the CNS, and (II) granule cells in the dentate gyrus. These results and our ongoing efforts demonstrate the importance of systematic molecular approaches to understanding cellular organization and dynamics in tissues.

    G-INCPM-Special Seminar - Prof. Yaron Shav-Tal, Faculty of Life Sciences & Nano-medicine Research Center, Institute of Nanotechnology and Advanced Materials, Bar-Ilan University - "Quantifying mRNA transcription on single alleles in single cells"

    Date:
    08
    Wednesday
    March
    2017
    Lecture / Seminar
    Time: 11:00-12:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Yaron Shav-Tal
    Organizer: Faculty of Biochemistry
    Abstract: I will describe approaches used to follow and quantify transcription kinetics fr ...I will describe approaches used to follow and quantify transcription kinetics from single genes in fixed and living cells, using single-molecule RNA FISH and live-cell imaging. These studies have allowed us to examine transcription at high resolution during the cell cycle and to reveal new levels of regulation. We have also generated a method to tag endogenous genes on the mRNA and protein levels, and this has allowed us to use RNA FISH to differentiate between the transcriptional activity of various alleles of the same gene in single cells, to characterize a cellular response to stress, and to screen for compounds that interfere with the stress response.

    Designed by Nature: Reduced Protein Stability Prevents Promiscuous Protein Binding The Case of TEM1-β-Lactamase

    Date:
    07
    Tuesday
    March
    2017
    Lecture / Seminar
    Time: 10:30-11:00
    Location: Wolfson Building for Biological Research
    Lecturer: Ruth Khait
    Organizer: Department of Biomolecular Sciences
    Abstract: Protein-protein interactions play important roles in most cellular processes. Pr ...Protein-protein interactions play important roles in most cellular processes. Proteins interact through chemical and structural complementarity of their mutual binding sites. Amino acids found in physical proximity form non-covalent interactions that stabilize the complex. Here we studied the evolution of PPI interfaces applying directed in vitro evolution on a random TEM library expressed on yeast surface. Our study focused on two specific questions: 1) How plastic is a well-defined PPI interface? For that purpose the TEM library was softly selected against its high affinity binder BLIP and analyzed by deep sequencing. 2) Is it possible to evolve new PPIs? Here the monomeric TEM library was selected against TEM-WT and other proteins to create new binders. Our results show that PPI interfaces are plastic and easily formed, hence evolution must actively act to prevent promiscuous protein binding. One mechanism which seems to be applied by nature for that purpose is keeping wild type proteins below their potential stability in a way that they are easily destabilized upon mutation.

    Personalized medicine for type 2 diabetes: Are we there?

    Date:
    05
    Sunday
    March
    2017
    Lecture / Seminar
    Time: 15:00-16:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Hilla Knobler
    Organizer: Life Sciences

    G-INCPM-Special Seminar - Dr. Bruce Lefker, Medicinal Chemistry Specialist, Visiting Scientist, Pfizer - "Validation of Novel Biological Targets: A Medicinal Chemist's View

    Date:
    28
    Tuesday
    February
    2017
    Lecture / Seminar
    Time: 11:00-12:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Dr. Bruce Lefker
    Organizer: Faculty of Biochemistry
    Abstract: Validation of hypotheses is an essential part of the scientific process. To val ...Validation of hypotheses is an essential part of the scientific process. To validate novel biological targets, a range of powerful biological approaches have emerged and are being leveraged (eg CRISPR, siRNA, antisense, antibodies, etc). In addition to these biological approaches, small molecule “chemical probes” have proven to be an extremely valuable orthogonal approach for validation. Also, successful generation of a small molecule chemical probe increases the confidence that a target is druggable, and can enable demonstration of therapeutically useful effects in animal models and ultimately humans. Of note to this audience is that the majority of new biological targets that led to novel medicines were discovered in academia. The G-INCPM at the Weizmann has established a drug discovery unit which can screen large collections of small molecules against novel biological targets or phenotypes in whole cells. A medicinal chemistry capability has recently been added to the Institute with the goal of increasing the value that will be derived from these ongoing screening efforts. The newly formed Medicinal Chemistry Unit is working closely with Biologists (at the Weizmann and other Institutes in Israel), and the High Throughput Screening Unit to interpret the output from screens, triage the output, and then optimize the most attractive hit matter. This lecture will present a definition of a “chemical probe” and our rationale for generating chemical probes. We will also discuss some of the common pitfalls in following up HTS hits, and the approaches being utilized to generate quality probes from screening campaigns.

    G-INCPM-Special Seminar - Prof. Paul Brennan, Associate Professor of Medicinal Chemistry, Principal Investigator, SGC & Target Discovery Institute, Head of Chemistry, Alzheimer's Research UK Oxford Drug Discovery Institute

    Date:
    08
    Wednesday
    February
    2017
    Lecture / Seminar
    Time: 11:00-12:15
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Paul Brennan
    Organizer: Faculty of Biochemistry
    Abstract: Epigenetics is the study of heritable changes in phenotype that are not encoded ...Epigenetics is the study of heritable changes in phenotype that are not encoded in an organism’s DNA. Epigenetic effects due to persistent changes in gene transcription have been linked to chemical modification of DNA and the proteins that package and regulate DNA in the nucleus, histones. One of the major post-translational modifications of histones is acetylation of lysine residues prevalent in histone tails. The principal readers of histone acetyl lysine marks are bromodomains (BRDs), which are a diverse family of over sixty evolutionary conserved protein-interaction modules. Proteins that contain BRDs have been implicated in the development of a large variety of diseases, including cancer and inflammation. In order to decipher the complex biology of bromodomains and provide evidence linking specific bromodomain targets to disease, we are discovering selective, cell active small molecule inhibitors of bromodomains.

    Personalized Cancer Nano-Medicines

    Date:
    06
    Monday
    February
    2017
    Lecture / Seminar
    Time: 14:00-15:00
    Title: Special Guest Seminar
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Avi Schroeder
    Organizer: Department of Biological Regulation
    Abstract: The field of medicine is taking its first steps towards patient-specific care. O ...The field of medicine is taking its first steps towards patient-specific care. Our research is aimed at tailoring treatments to address each person’s individualized needs and unique disease presentation. Specifically, we are developing nanoparticles that target disease sites, where they perform a programmed therapeutic task. These systems utilize molecular-machines and cellular recognition to improve efficacy and reduce side effects. Nanoparticles have many potential benefits for treating cancer, including the ability to transport complex molecular cargoes, as well as targeting to specific cell populations. The talk will describe principles for developing lipid nanoparticles that can be remotely triggered to release their payload in disease sites. Two examples will be described: the first involves a nanoscale theranostic system for predicting the therapeutic potency of cancer medications. The system provides patient-specific drug activity data with single-cell resolution. The system makes use of barcoded nanoparticles to predict the therapeutic effect different drugs will have on the tumor microenvironment. The second system makes use of enzymes, loaded into a biodegradable chip, to perform a programed therapeutic task – surgery with molecular precision. Collagenase is an enzyme that cleaves collagen, but not other tissues. This enzyme was loaded into the biodegradable chip and placed in the periodontal pocket. Once the collagenase releases from the chip, collagen fibers that connect between the teeth and the underlying bone are relaxed, thereby enabling enhanced orthodontic corrective motion and reducing pain. This new field is termed BioSurgery. The clinical implications of these approaches will be discussed.

    From Single Nuclei RNA-Sequencing to Dynamics of Neuronal Regeneration

    Date:
    29
    Sunday
    January
    2017
    Lecture / Seminar
    Time: 11:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Naomi Habib
    Organizer: Department of Neurobiology
    Details: Host: Prof. Alon Chen alon.chen@weizmann.ac.il tel: 4490 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: Throughout adult life, adult neuronal stem cells (NSCs) continuously generate ne ...Throughout adult life, adult neuronal stem cells (NSCs) continuously generate neurons in discrete brain regions. I am interested in harnessing this natural regenerative process for repairing the diseased and aging brain. To effectively use this regenerative capacity in a clinical setting requires first an advanced understanding of NSCs, adult neurogenesis and neuronal regeneration during neurodegenerative diseases and aging. Study of these areas, however, is challenging, as it requires profiling rare continuous processes in the adult brain. To this end, I developed sNuc-Seq, a method for profiling RNA in complex tissues with single nuclei resolution by RNA-sequencing, and Div-Seq, for profiling RNA in individual dividing cells. I applied sNuc-Seq to study the adult hippocampus brain region, revealing new cell-type specific and spatial expression patterns. I then applied Div-Seq to track transcriptional dynamics of newborn neurons within the adult hippocampal neurogenic region and to identify and profile rare newborn GABAergic neurons in the adult spinal cord. I am currently developing follow-up technologies to sNuc-Seq and applying them to study the cross-talk between neurons, NSCs, glia and immune cells during neurodegenerative diseases and its role in inhibiting or promoting regeneration. I will continue to work towards advancing our ability to mitigate and even reverse neurodegenerative disease and age-related pathologies. Incorporating in my work techniques from molecular neuroscience, single cell genomics, genome engineering and computational biology.

    Molecular classification of cells in the mouse brain revealed by single-cell RNAseq

    Date:
    28
    Wednesday
    December
    2016
    Lecture / Seminar
    Time: 09:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Amit Zeisel
    Organizer: Department of Neurobiology
    Details: Host: Prof. Alon Chen alon.chen@weizmann.ac.il tel: 4490 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Abstract: The mammalian central nervous system is arguably the most complex system studied ...The mammalian central nervous system is arguably the most complex system studied in biology. Normal function of the brain relies on the assembly of a diverse set of cell-types, including most prominently neurons, but also glial cells and vasculature. We developed and applied large-scale single-cell RNA sequencing for unbiased molecular cell-type classification in various regions of the mouse brain. I will describe our initial work on the somatosensory cortex and hippocampus CA1, and later give examples about heterogeneity in the oligodendrocyte lineage across the CNS. These results and our ongoing efforts demonstrate how detailed information about cell-types in the brain may contribute to understand brain function.

    The regulatory role of short structural variants and the implication to neurodegenerative diseases in aging

    Date:
    22
    Thursday
    December
    2016
    Lecture / Seminar
    Time: 10:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Ornit Chiba-Falek
    Organizer: Department of Molecular Genetics
    Abstract: In the post genome-wide association studies (GWAS) era we are shifting gears tow ...In the post genome-wide association studies (GWAS) era we are shifting gears toward translation of genetic disease loci to molecular mechanisms of pathogenesis and pinpointing the causal genetic factors and their functional effects. It has been suggested that changes, even subtle, in the expression levels of wild-type genes in the brain can, over years, lead to neurodegenerative diseases. Moreover, differences in gene expression profiles between brain tissues from neurodegenerative disease patients compared to healthy controls have been reported. Short structural variants (SSVs) are short genomic variants (

    G-INCPM-Special Seminar - Dr. Fabien Vincent, Senior Molecular Pharmacology & Drug Discovery Scientist, Pfizer - "Practical Phenotypic Screening"

    Date:
    15
    Thursday
    December
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Michael and Anna Wix Auditorium
    Lecturer: Dr. Fabien Vincent
    Organizer: Faculty of Biochemistry
    Abstract: Phenotypic screening is experiencing a Renaissance in the pharmaceutical industr ...Phenotypic screening is experiencing a Renaissance in the pharmaceutical industry, based on its successful track record in delivering first-in-class medicines stemming from novel biology. Although phenotypic screening may appear at first sight to be similar to target-based screening, there are some significant differences between the two approaches. These need to be properly considered and addressed to ensure the greatest likelihood of success for phenotypic screening programs. This presentation will cover the following questions with the aim of providing practical information: What is the rationale for conducting phenotypic screens? When do they provide the most value? Not all phenotypic assays are created equal: What are the characteristics of the best assays? Which libraries should be screened and why? What are some key considerations and strategies for phenotypic hit triage? What are some key considerations and strategies for mechanism identification and validation?

    G-INCPM - Special Seminar - Mr. Daniel G. Sipes, Director, Advanced Automation Technologies, Genomics Institute of the Novartis, Research Foundation (GNF) - "Advances in Automation to Accelerate Drug Discovery at GNF"

    Date:
    30
    Wednesday
    November
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Mr. Daniel G. Sipes
    Organizer: Department of Biomolecular Sciences
    Abstract: At GNF, we have been developing and implementing high throughput miniaturized as ...At GNF, we have been developing and implementing high throughput miniaturized assays and robotic systems to enable drug discovery for over 15 years. This presentation will review how our platform systems have adapted to and incorporated the latest scientific and technical advancements. Our flagship high throughput screening systems, capable of running hundreds of thousands of compounds per day against cellular or biochemical assays, continue to demonstrate their effectiveness. We have continued to expand the utility of GNF-built automation, as well as other commercially available technologies, to enable cost effective and rapid cell-based profiling of small molecules as well as biologics. In addition, this approach has allowed scientists to run primary cell assays on a scale not otherwise practical. Examples will include instruments and automation to greatly accelerate high-content phenotypic assays and flow cytometry. The latest advancements in reagent dispensing, detection and robotics will further the deployment of these technologies into areas such as highly multiplexed transcriptional readouts and Next Gen Sequencing.

    In vivo veritas – Using CRISPR genome editing to model cancer in mice

    Date:
    17
    Thursday
    November
    2016
    Lecture / Seminar
    Time: 11:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Daniel Schramek
    Organizer: Department of Molecular Genetics
    Abstract: Modern Genetics is revealing virtually all the genetic and epigenetic alteration ...Modern Genetics is revealing virtually all the genetic and epigenetic alterations associated with human malignancies. Mining this information for Precision Medicine is predicated on weeding out ‘bystander’ mutation and identifying the ‘driver’ mutations responsible for tumor initiation, progression and metastasis, as only the latter have diagnostic and therapeutic value. Secondly, we have to elucidate how driver mutations alter the fundamental molecular pathways governing tissue growth and identify actionable nodes within a given cancer gene network that can be exploited therapeutically. The massive quantity of data emerging from cancer genomics therefore demands a corresponding increase in the efficiency and throughput of in vivo models to comprehensively assess all putative cancer genes. We therefore developed a versatile functional genomics toolbox that enables us to generate and analyze thousands of somatic gene knock-out or overexpression clones within a single animal in a matter of weeks. Ultrasound-guided in utero injections allow us to selectively transduce fluorescently-labeled lentiviral CRISPR or ORF libraries into various organs of living mouse embryos. Subsequent mosaic analysis, next-generation sequencing and library barcode deconvolution enables us to identify genes that regulate proliferation, differentiation and survival. Of note, this analysis not only assess the gene function in an physiological and immune-competent microenvironment, but can also be combined with any mouse model and treatment schedule to faithfully model human malignancies. Using this technique, we have completed several proof-of-concept screens and elucidated several novel tumor suppressor genes in Head&Neck. Currently, we are performing several multiplexed in vivo CRISPR screens to uncover context-specific cancer vulnerabilities, novel immune regulators and genes that confer resistance to chemo- or targeted therapies. In this seminar, I will highlight the utility of direct in vivo screening to integrate human cancer genomics and mouse modeling for rapid and systematic discovery of cancer driver mutations and novel cancer vulnerabilities.

    The Pan and Core Genome of Populus trichocarpa

    Date:
    07
    Monday
    November
    2016
    Lecture / Seminar
    Time: 10:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Gerald Tuskan
    Organizer: Department of Molecular Genetics
    Abstract: Abstract: The genetic diversity of a species is the sum of the diversity found i ...Abstract: The genetic diversity of a species is the sum of the diversity found in all individuals of that species. One way to estimate the diversity of species is by resequencing diverse accessions and aligning the reads to a reference genome. While this approach readily identifies SNPs and small indels with respect to a reference genome, it underestimates total genomic diversity contained within a species because highly divergent regions align poorly to the reference and any sequence not found in the reference will be missed entirely. There is a considerable amount of structural variation including copy number variants (CNVs) and presence/absence variants (PAVs), which alter the total amount of genomic sequence found in individuals. Thus, the true extent of diversity within a plant species is largely unknown. De novo genome assemblies and annotation can be used to more accurately estimate the true genomic diversity within a species. Pan-genomes in other plant species have been created before but at a smaller scale. Previous studies used around 50 genomes to create the pan-genome. Here we present one of the largest studies with more than a thousand genotypes of Populus trichocarpa. We applied both approaches of reference-based alignment, as well as de novo assembly of unmapped reads, to create a pan-genome that contains all the diversity found in the accessions sequenced. Analysis of this data yielded a high-confidence Populus trichocarpa pan-genome that includes more 20,000 additional gene models relative to the reference. We have also used RNA Sequencing for generating expression profiles of individual accessions, with ca. 75% of the new gene models having expression evidence. We have used this RNA-Seq data to generate the pan-transcriptome profile of Populus trichocarpa and have identified new splice-site variants, found alternate exon-intron structures within the reference gene models and promoted alternate splice-site variants as the primary gene model.

    G-INCPM - Special Seminar - Prof. Mag. Dr. Andreas J. Kungl, Institute of Pharmaceutical Chemistry, Karl-Franzens Univ. of Graz, Austria

    Date:
    19
    Monday
    September
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Title: "Therapeutically targeting glycosaminoglycans by chemokine decoys: evidence from in vitro, in vivo and phase 1 clinical data"
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Prof. Mag. Dr. Andreas J. Kungl
    Organizer: Department of Biomolecular Sciences
    Abstract: Glycosaminoglycans (GAGs) are linear, highly charged/sulfated polysaccharides wh ...Glycosaminoglycans (GAGs) are linear, highly charged/sulfated polysaccharides which were shown by us and others, applying pull-down proteomics, to be involved in binding and structurally activating a multitude of proteins. Specifically endothelial GAGs such as heparan sulphate (HS) play an important role in chemokine presentation to chemokine GPC receptors on leukocytes and transportation across the endothelial barrier. As such, the chemokine-GAG interaction interface is involved in a plethora of diseases like acute/chronic inflammation and tumorigenesis. We have engineered several chemokines with respect to their GAG binding and GPC receptor activity so that they become dominant-negative decoys thereby antagonising the biological activity of their wild type counterparts with excellent dose-response profiles in vitro and in vivo. Recent data from CXCL8, CXCL12, and CCL2 chemokine mutants in inflammatory and oncology models will be presented.

    G-INCPM - Special Seminar - Prof. Eran Hornstein, the Dept. of Molecular Genetics, Weizmann - "MicroRNA Dysfunction in Neurodegeneration"

    Date:
    07
    Wednesday
    September
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Prof. Eran Hornstein, Dept. of Molecular Genetics, Weizmann
    Organizer: Department of Biomolecular Sciences
    Abstract: Interest in RNA dysfunction in ALS recently aroused upon discovering causative m ...Interest in RNA dysfunction in ALS recently aroused upon discovering causative mutations in RNA-binding protein genes. Focusing on the causes and consequences of miRNA dysregulation in amyotrophic lateral sclerosis (ALS) we will understand how advances in sequencing and molecular technologies enable deciphering the contribution of noncoding RNAs to Neurodegeneration. In the past, we identified extensive down-regulation of miRNA levels is a common molecular denominator for multiple forms of human ALS. We further demonstrated that pathogenic ALS-causing mutations are sufficient to inhibit miRNA biogenesis at the Dicing step. These works position miRNAs downstream of the initiating mutations that drive ALS and encourage testing what are the specific miRNAs that play roles in motor neurons and whether mutations in miRNA genes will be able to causatively initiate the disease.

    Full humanisation of the mouse immunoglobulin loci

    Date:
    25
    Thursday
    August
    2016
    Lecture / Seminar
    Time: 10:00
    Location: Wolfson Building for Biological Research
    Lecturer: Prof. Allan Bradley
    Organizer: Department of Neurobiology
    Details: Host: Prof. Michal Schwartz michal.schwartz@weizmann.ac.il tel: 2467
    Abstract: Professor Bradley is internationally recognized as a pioneer in developing the t ...Professor Bradley is internationally recognized as a pioneer in developing the techniques, technology and tools for genetic manipulation in the mouse over more than 3 decades. He served as Director of the Welcome Trust Sanger Institute from 2000 to 2010. He was honored by election to the fellowship of the Royal Society in 2002. Among many projects that Dr. Bradley has established and led, is the international project to systematically knockout all genes in the mouse genome, the most ambitious use of ES-cell technology ever attempted. Over the last 30 years, Dr. Bradley has authored more than 280 publications. In his lecture, Dr. Bradley will be describing the scientific history and the technology behind the creation of the Kymouse strains which are transgenic for the total human immunoglobulin gene diversity. The platform provides a valuable means to isolate therapeutic monoclonal antibodies. Kymab has also developed single B cell-based methods to capture both the heavy and light chains of antibodies at scale. Combined with deep sequencing of millions of B cells we are able to build networks of histories of B cell families which we use to isolate rare antibodies with unique properties. The combined use of Kymouse with B cell network analysis, facilitates vaccine antigen discovery and predictive pre-clinical assessment of candidate vaccine antigens prior to clinical trials in humans.

    G-INCPM - Special Seminar - Prof. Matthias Nees, Institute if Biomedicine, Univ. of Turku, Finland - "Combining Speed of Analysis with Complex Tissue Models for Physiologically Relevant High-Content Screening"

    Date:
    24
    Wednesday
    August
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Prof. Matthias Nees
    Organizer: Department of Biomolecular Sciences
    Abstract: In vitro model systems used in drug discovery typically do not address the compl ...In vitro model systems used in drug discovery typically do not address the complex architecture of human disease tissues. Only few approaches aim to faithfully recapitulate the complexity, heterogeneity and cellular dynamics e.g. in epithelial tissues and carcinomas. The most important aspects relate to the (tumor-) microenvironment, including cell-cell and cell-matrix interactions, inflammation and the role of stromal components. All of these elements can have a significant, but often underestimated impact on differentiation, normal and abnormal tissue functions, or drug response versus drug resistance. The basis for performing informative high content screening campaigns with such complex tissue models in vitro is access to fast, automated image analysis. We have developed a software platform (AMIDA, Automated Morphometric Image Data Analysis) that captures a large number of morphometric features in an unsupervised fashion. This approach enables us to capture much of the inherent complexity and dynamics of microtissues, yet still allows high experimental throughput. This screening platform is ideally suited for investigating a broad spectrum of defined, biological questions in drug discovery as well as personalised medicine. Technology and screening platform are applicable for multiple types of research, such as quantitatively measuring the response of primary cancer cells or cell lines to drugs, siRNAs or other perturbations. Image analysis algorithms can also be adapted towards specific applications in neurodegenerative diseases, stem cell research, and to quantitate the interaction of epithelial cells with immune, adipocytes or mesenchymal stem cells.

    G-INCPM Special Seminar - Dr. Gad Asher, Dept. of Biomolecular Sciences, Weizmann - "A Circadian View of Nutrition and Metabolism

    Date:
    10
    Wednesday
    August
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Dr. Gad Asher
    Organizer: Department of Biomolecular Sciences
    Details: The seminar is being held in the Weissman Auditorium due to renovations at the site of the G-INCPM Auditorium
    Abstract: Circadian clocks are positioned at the cross road between nutritional cues and m ...Circadian clocks are positioned at the cross road between nutritional cues and metabolic control. Thus, studying metabolism from a temporal and spatial perspective provides a unique niche that is expected to unveil novel fundamental principles related to basic metabolism and their nutritional control. In recent years my lab employed different methodologies, from biochemical approaches that identify protein-metabolite interactions through measurements of metabolic outputs in intact cells and living animals to high-throughput proteomics and metabolomics, to examine temporal and spatial aspects of metabolism. During my talk, I will discuss several examples emerging from our work on different groups of metabolites (e.g., lipids, polyamines) and on cellular metabolic processes (e.g., mitochondrial function) that shed new light in respect to their temporal and spatial intracellular organization and their nutritional control by different dietary regimens.

    MCB - Student Seminar

    Date:
    05
    Tuesday
    July
    2016
    Lecture / Seminar
    Time: 12:15-14:00
    Title: The role of the G-protein coupled receptor PAC1 in the regulation of homeostasis and behavior and Understanding single-cell gene expression data using Pareto optimality theory
    Location: Wolfson Building for Biological Research
    Lecturer: Dr. Jakob Biran and Dr. Yael Korem
    Organizer: Department of Molecular Cell Biology

    Using single-cell transcriptomics to study cell fate decisions in early mammalian development

    Date:
    01
    Wednesday
    June
    2016
    Lecture / Seminar
    Time: 12:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Dr. John Marioni
    Organizer: Department of Immunology

    The ins and outs of subaerial lithotrophic biofilm in arid and hyper-arid environments

    Date:
    29
    Sunday
    May
    2016
    Lecture / Seminar
    Time: 11:00
    Location: Sussman Family Building for Environmental Sciences
    Lecturer: Nimrod Wieler
    Organizer: Department of Earth and Planetary Sciences
    Abstract: Rock surfaces support microbial communities that may be involved in weathering p ...Rock surfaces support microbial communities that may be involved in weathering processes. In arid and hyper-arid environments microbes dominate rock surfaces and were linked to weathering because the scarcity of water excludes classical mechanisms that erode rocks. We studied subaerial biofilms coating arid rocks, focusing on sedimentary rocks that feature comparable weathering morphologies but different lithologies. We hypothesized that weathering is fashioned by salt erosion and mediated by biofilms that play dual roles: stabilizing the rock surfaces by coating, and enhancing salt crystallization by preventing rapid desiccation (thus mitigating and facilitating erosion processes, respectively). We used a combination of microbial and geological techniques to characterize the rocks morphologies and their subaerial biofilms. Deep sequencing and microscopy analyses suggest that bacterial diversity is low, dominated by Proteobacteria, Cyanobacteria and Actinobacteria. Together these phyla formed laminar biofilms that secrete extracellular polymeric substances to aggregate microfabrics and mitigate desiccation, reducing water loss by over 40%. The biofilm was detected only in rocks exposed to the atmosphere, present distinct architecture and burrowed up to 9 mm beneath the surface, protected by sedimentary deposits. A closer inspection revealed that the composition of the biofilm was tightly linked to dust bacterial communities but distinct from soil communities. Moreover, the biofilm composition changed according to the rock location rather than its’ lithology, suggesting that microclimate (dew, relative humidity and radiation) play an important role in arid weathering. Our results contradict common dogmas that considered biofilms as degrading agents and propose their role as mitigators of geomorphic processes.

    G-INCPM-Special Seminar - Yael Malkinson Weiss, MD PhD, Executive Director Business Development, Ultragenyx Pharmaceutical, Novato CA - "Developing therapies for rare genetic diseases: weighing traditional versus novel therapeutic modalities"

    Date:
    29
    Sunday
    May
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Yael Malkinson Weiss, MD PhD
    Organizer: Department of Biomolecular Sciences
    Abstract: Developing therapies for the treatment of rare genetic disease is frequently per ...Developing therapies for the treatment of rare genetic disease is frequently perceived to be simpler and with a lower risk than that associated with larger indications. This perception stems from the fact that many of these are monogenic, with predictable genetic effects and clear mechanisms, thus it should be straightforward to replace the defective protein. Since the diseases are usually severe the benefit is large, and in many cases, the rarer the disease, the smaller the clinical trials that are required for registration are. However, there are over 7,000 genetic diseases with an even larger number of genes affected. The initial approach of protein replacement therapies can be successful but is limited to a relatively small diseases in which the defective proteins are localized in a subset of cellular organelles to which therapeutic proteins will naturally target (lysosome for example). Most of the diseases treatable with traditional protein replacement are becoming very crowded for how small the treatable patient population is. Thus - other solutions need to be considered for the thousands of diseases for which direct proteins replacement is not a viable approach. Ultragenyx is a biotech company focused on development of therapies for rare genetic diseases. The company’s approach to building its pipeline and deciding how and when to include traditional (protein replacement therapies, small molecules) or new (nucleic acid based therapies) therapeutic modalities will be presented and examples will be discussed.

    MCB Student Seminar

    Date:
    24
    Tuesday
    May
    2016
    Lecture / Seminar
    Time: 12:30
    Title: Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens Massively parallel interrogation of the effects of gene expression levels on cellular fitness
    Location: Wolfson Building for Biological Research
    Lecturer: Shelly Kalaora; Leeat Yankielowicz-Keren
    Organizer: Department of Molecular Cell Biology

    G-INCPM-Special Seminar - Prof. Rivka Inzelberg, Specialist in Neurology and Movement Disorders, Department of Neurology and Neurosurgery, Faculty of Medicine, Tel-Aviv University - "Parkinson’s disease: lessons from observations over time"

    Date:
    24
    Tuesday
    May
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Rivka Inzelberg
    Organizer: Department of Biomolecular Sciences
    Abstract: Epidemiological studies show an atypical cancer pattern in patients with Parkins ...Epidemiological studies show an atypical cancer pattern in patients with Parkinson’s disease. While many cancers are rarer than the general population in Parkinson’s cohorts, some cancers and especially melanoma are observed at higher than expected rates. Nowadays, several PARK genes have been found to be associated with familial and sporadic Parkinson’s disease. The possible contribution of PARK genes to the atypical cancer pattern of Parkinson’s disease patients and to melanoma co-occurrence will be discussed. The second part of the talk focuses on the awakening of novel artistic skills in patients with Parkinson’ disease. The appearance of previously unknown creativity may accompany neurodegeneration. Despite motor symptomatology, Parkinson’s patients develop fine artistic capabilities after the diagnosis of the disease. Observations form the clinic and mechanisms will be discussed.

    G-INCPM-Special Seminar - Alessandro Spada, Manager Southern Europe, Dotmatics Ltd.

    Date:
    24
    Tuesday
    May
    2016
    Lecture / Seminar
    Time: 09:00-12:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Alessandro Spada
    Organizer: Department of Biomolecular Sciences
    Abstract: Dotmatics would like to invite you to register to our upcoming seminar that will ...Dotmatics would like to invite you to register to our upcoming seminar that will take place in Rehovot on the 24th of May 2016 inside the Weizmann Institute (Botnar auditorium, Belfer building registration starting at 9.00 am). The event organized by Dotmatics in collaboration with the Weizmann Institute is an opportunity for an introduction to the Dotmatics Solutions in the space of: - Chemistry and Biologics Discovery Informatics Database Management - Electronic Laboratory Notebook for R&D - Compound and Reagent Management - Data Analysis and Visualization - Activities and Compound Progression Management - Scientific collaboration in shared research projects We believe this event will provide you an introduction on how Dotmatics, through its 10 year trajectory, has become one of the leader supplier of Informatics Solution in the challenging field of Life Science and Chemical/Agrochemical R&D. We will present use cases and we will answer to your questions bringing all our experience in implementing solutions from small biotech to large pharmaceutical industries. If you are interested please use the following link for registration: https://www.eventbrite.co.uk/e/dotmatics-seminar-israel-tickets-24314743051 The Agenda: 9.00 am Coffee and registration 9.30 am Open and welcome – Dotmatics - Alessandro Spada 9.45 am Dotmatics – Supporting “The Research Workflow” – Alessandro Spada and Ronen Peleg 10.15 am Compound Management using the Dotmatics Suite – Weizmann Institute of Science, Galit Choen, Compound Management HTS Unit 10.45 am Coffee Break 11.15 am Dotmatics – Streamline Collaborative Research – Alessandro Spada and Ronen Peleg 11.45 pm Wrap up and closing remarks For any inquiry please send an email to Alessandro.Spada@Dotmatics.com and we will be more than happy to answer any of your question/curiosity. Looking forward to meet you soon My best regards Alessandro Spada Manager Southern Europe

    Deciphering membrane-protein energetics using deep sequencing

    Date:
    17
    Tuesday
    May
    2016
    Lecture / Seminar
    Time: 10:30-11:00
    Location: Wolfson Building for Biological Research
    Lecturer: Dr. Assaf Elazar
    Organizer: Department of Biomolecular Sciences
    Abstract: Abstract (form the eLife paper:) ): Insertion of helix-forming segments into the ...Abstract (form the eLife paper:) ): Insertion of helix-forming segments into the membrane and their association determines the structure, function, and expression levels of all plasma membrane proteins. However, systematic and reliable quantification of membrane-protein energetics has been challenging. We developed a deep mutational scanning method to monitor the effects of hundreds of point mutations on helix insertion and self-association within the bacterial inner membrane. The assay quantifies insertion energetics for all natural amino acids at 27 positions across the membrane, revealing that the hydrophobicity of biological membranes is significantly higher than appreciated. We further quantitate the contributions to membrane-protein insertion from positively charged residues at the cytoplasm-membrane interface and reveal large and unanticipated differences among these residues. Finally, we derive comprehensive mutational landscapes in the membrane domains of Glycophorin A and the ErbB2 oncogene, and find that insertion and self-association are strongly coupled in receptor homodimers.

    G-INCPM-Special Seminar - Prof. Hagit Eldar-Finkelman, Dept. of Human Molecules Genetics & Biochemistry, Sackler School of Medicine, Tel-Aviv University - "Glycogen synthase kinase-3: From Evolution to Drug Discovery"

    Date:
    13
    Wednesday
    April
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Hagit Eldar-Finkelman
    Organizer: Department of Biomolecular Sciences
    Abstract: The serine threonine kinase glycogen synthase kinase-3 (GSK-3) is a promising dr ...The serine threonine kinase glycogen synthase kinase-3 (GSK-3) is a promising drug discovery target in diverse pathological disorders. GSK-3 was initially implicated in glycogen metabolism, however, the enzyme has surprised us with a host of additional regulated processes related to other disease states including cancer, psychiatric disorders, and neurodegenerative diseases. Indeed, treatment with GSK-3 inhibitors produces significant therapeutic benefits in multiple disease-animal models. How one enzyme can be involved in such diverse processes is not fully clear. It is possible that common targets regulated by GSK-3 have different biological impacts in different tissues and/or different cellular conditions. To tackle this problem we use cell systems that either overexpress GSK-3 or inhibit its activity selectively and screen for potential downstream factors in a ‘hypothesis free’ approach. Our studies identified the mammalian target of rapamycin (mTOR) as a GSK-3 target. Accordingly GSK-3 was found to regulate autophagy and lysosomal acidification. These findings suggested a new paradigm in which GSK-3 serves as a molecular switch of biosynthesis and protein turnover. Hence, inhibition of GSK-3 re-balances protein homeostasis, often impaired in pathogenesis, which in turn ameliorates disease severity and disease progression. An additional, and complementary, aspect of our work is development of selective GSK-3 inhibitors. We developed a pipeline of substrate competitive GSK-3 inhibitors that show high selectivity and excellent pharmacological properties. The strategy for design of selective GSK-3 inhibitors and screening for potential new inhibitors will be also discussed.

    G-INCPM International Workshop 2016

    Date:
    04
    Monday
    April
    2016
    -
    05
    Tuesday
    April
    2016
    Conference
    Time: 08:00
    Location: David Lopatie Conference Centre

    G-INCPM International Workshop 2016

    Date:
    04
    Monday
    April
    2016
    Conference
    Time: 00:00
    Location: David Lopatie Conference Centre

    TCR sequencing reveals the architecture of the T cells compartments

    Date:
    17
    Thursday
    March
    2016
    Lecture / Seminar
    Time: 14:30-15:00
    Title: THE OFER LIDER RESEARCH-IN-PROGRESS SEMINAR 2016 IMMUNOLOGY DEPARTMENT
    Location: Wolfson Building for Biological Research
    Lecturer: Michal Mark
    Organizer: Department of Immunology

    MCB Student Seminar

    Date:
    15
    Tuesday
    March
    2016
    Lecture / Seminar
    Time: 12:30-13:30
    Title: Dynamic proteomics of HSV-1 infected cells reveals effects of cellular heterogeneity on viral infection outcome Neuron-glia interactions in Drosophila melanogaster mushroom body development
    Location: Wolfson Building for Biological Research
    Lecturer: Dr. Nir Drayman & Neta Kollet
    Organizer: Department of Molecular Cell Biology

    G-INCPM-Special Seminar - Irit Paz, Ph.D, GLocal Sales Manager, Takara Bio Europe SAS - SMARTer® Solutions for Next-Gen Sequencing

    Date:
    02
    Wednesday
    March
    2016
    Lecture / Seminar
    Time: 10:00-11:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Irit Paz, Ph.D
    Organizer: Department of Biomolecular Sciences
    Abstract: Next-generation sequencing (NGS) has increased our understanding of biological p ...Next-generation sequencing (NGS) has increased our understanding of biological phenomena and human disease by enabling highly sensitive transcriptome analysis across a large dynamic range of RNA expression levels. As exciting new applications for NGS emerge, Clontech continues to develop powerful new tools for life science research by improving and building upon its core technologies. A common feature of Clontech® NGS kits is SMART® technology, which harnesses the template-switching activity of customized reverse transcriptases to enable researchers to analyze their most challenging samples, such as ultra-low input or single-cell RNA, noncoding RNA, and RNA from degraded samples. In particular, single-cell RNA-seq is one of the fastest-growing applications of NGS, and the SMARTer Ultra® Low mRNA-seq family of products, featuring a highly sensitive, dT-primed mechanism, has become the gold standard for this type of analysis. The newest generations of ultra-low input/single-cell mRNA-seq and picogram-input total RNA-seq kits have brought increased sensitivity to SMART technology by improving upon the SMART-Seq® method and incorporating locked nucleic acid (LNA) technology. Expanding applications for SMART technology have led to a ligation-free method for generating ChIP (chromatin immunoprecipitation) sequencing libraries. This seminar will take you on a tour of these new technologies and highlight ongoing research on a variety of NGS applications, including single-cell RNA-seq.

    G-INCPM-Special Seminar: Prof. Emeritus Ira Krull, Department of Chemistry and Chemical Biology, Northwestern University, USA - "Top-Down Protein Sequencing by Mass Spectrometry, Quo Vadis?

    Date:
    15
    Monday
    February
    2016
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Emeritus Ira Krull
    Organizer: Department of Biomolecular Sciences

    G-INCPM Special Seminar - Dr. Nir London, Dept. of Organic Chemistry, Weizmann - "Covalent Docking of Large Chemical Libraries for the Discovery of New Inhibitors"

    Date:
    03
    Wednesday
    February
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Dr. Nir London
    Organizer: Department of Biomolecular Sciences
    Abstract: Small molecules are invaluable tools for the investigation of biology. However, ...Small molecules are invaluable tools for the investigation of biology. However, discovering new molecules to specifically modulate a target protein is still one of the biggest challenges of chemical biology. Molecules that are able to form a covalent bond with their target often show enhanced selectivity, potency and utility for biological studies, but are yet harder to discover, as they are typically expunged from high throughput screening libraries. Computational methods can help bridge this gap. We developed a covalent docking method for the discovery of covalent probes. Applying this method prospectively to several protein targets we were able to discover potent covalent inhibitors (typically with

    G-INCPM Special Seminar - Prof. Yosef Yarden, Dept. of Biological Regulation, Weizmann - "Signaling and Therapy of Hard to Treat Cancers"

    Date:
    20
    Wednesday
    January
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Yosef Yarden
    Organizer: Department of Biomolecular Sciences
    Abstract: Tumor-specific combinations of oncogenic mutations often free cancer cells from ...Tumor-specific combinations of oncogenic mutations often free cancer cells from their reliance on growth factors. One important example comprises the epidermal growth factor receptor (EGFR) and its kin, HER2. In tumors, both EGFR and HER2 frequently display overexpression, internal deletions and point mutations. Accordingly, monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) specific to these receptors have been approved for clinical applications. My lecture will introduce EGFR and HER2 in the context of a signaling network comprising two additional receptors, HER3 and HER4, and 11 growth factors, all sharing an EGF-like structure and binding to HER family members. The principles of network biology, such as rewiring, robustness and pathway redundancy, translate to short–term responses to oncology drugs. In other words, patients treated with drugs intercepting EGFR or HER2 often develop resistance due to emergence of compensatory mechanisms. My lecture will exemplify these principles in context of several relatively hard to treat tumors. The tumors I will discuss include breast cancers, both HER2-enriched and triple-negative, ovarian cancer and advanced non-small cell lung tumors that acquired resistance to EGFR’s TKIs.

    G-INCPM Special Seminar - Prof. Karl Skorecki, MD FRCP (C) FASN, Annie Chutick Professor in Medicine (Nephrology), Technion & Director of Medical and Research Development, Rambam Health Care Campus - "Population Genetics of Kidney Disease"

    Date:
    06
    Wednesday
    January
    2016
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Karl Skorecki, MD FRCP (C) FASN
    Organizer: Department of Biomolecular Sciences
    Abstract: Karl Skorecki and his colleagues used a combination of population genetics and e ...Karl Skorecki and his colleagues used a combination of population genetics and evolutionary medicine approaches to identify two sets of genetic sequence variants in the APOL1 innate immunity gene which account for 70% of the 4-fold disparity in chronic kidney disease in populations of Sub-Saharan African ancestry. These variants rose to high allele frequency in the at-risk population due to past adaptive selection, which also facilitated population based disease risk gene discovery using admixture mapping. Odds ratios conferred by these variants range from 7 to 90 depending on epistatic and environmental interactions. Pathobiology, target identification, and drug discovery studies are now proceeding using a variety of experimental platforms and scientific collaborations which will be highlighted.

    A synthetic, single-cell approach to mammalian signaling, memory, and cell fate transition circuits

    Date:
    31
    Thursday
    December
    2015
    Lecture / Seminar
    Time: 10:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Michael Elowitz
    Organizer: Department of Molecular Genetics

    LC-MS/MS and Next Generation Sequencing for High-resolution analysis of the breadth and polarization of human antibody repertoires

    Date:
    15
    Tuesday
    December
    2015
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Dr. Yariv Wine
    Organizer: Department of Structural Biology

    Probabilistic inference of immune repertoires diversity

    Date:
    16
    Monday
    November
    2015
    Lecture / Seminar
    Time: 14:15
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Yuval Elhanati
    Organizer: Department of Physics of Complex Systems
    Abstract: The adaptive immune system can recognize many different pathogens by maintaining ...The adaptive immune system can recognize many different pathogens by maintaining a large diversity of cells with different membrane receptors. We study the complex stochastic processes that generate and shape this ensemble of immune receptors developing probabilistic models from statistical inference of high throughput sequencing data. Our technique based on transfer matrices learns the probabilistic properties of the generation process, and finds it to be amazingly universal across individuals. We then model also selection pressures on the generated cells, in terms of the composition of their receptors, again finding universality, and reduction in diversity. In general our methods allows us to characterize and study the diversity distribution of immune repertoires using available sample data. This can be invaluable as a baseline for future study of the system as well as clinical applications, but might also expand our knowledge on statistical properties of interacting ensembles.

    G-INCPM-Special Seminar - Prof. Miguel Weil, Head of the Cell Screening Facility for Personalized Medicine, Department of Cell Research and Immunology, Tel-Aviv Univ. - Novel approach for Personalized Medicine of rare diseases

    Date:
    04
    Wednesday
    November
    2015
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Miguel Weil
    Organizer: Department of Biomolecular Sciences
    Abstract: Personalized medicine aims the tailoring of strategies to detect, treat, and pre ...Personalized medicine aims the tailoring of strategies to detect, treat, and prevent disease based on an individual’s genetic fingerprint or makeup. Although several advances have been made in molecular profiling technologies to obtain and analyze vast amount of personal information, this technologies has yet to prove their use for drug-personalized treatment. We have developed a novel approach that could solve this existing gap between the identification of disease biomarkers within the acquired personalized biological data and their potential for drug-personalized treatment. We use image based high content analysis (HCA) to identify the disease phenotype in cells from patients with neurodegenerative and rare diseases. This technology obtains the personal biological information from multiple images taken from thousands of cells isolated from skin biopsies of patients allowing us to identify specific disease signatures or disease phenotypes based on the ! individual’s cell biology. These disease signatures will enable us to screen thousands of drugs on patient cells and to isolate potential drugs for personalized treatment. This approach will contribute a great deal to the evolving field of personalized medicine in general and to the field of diagnosis and treatment of incurable neurodegenerative and rare diseases. The Cell Screening Facility for Personalized Medicine (CSFPM) which is part of the new Blavatnik Center for Drug Development (BCDD) at TAU, aims to find potential drugs for treatment of rare diseases like Amyotrophic Lateral Sclerosis (ALS), Familial Dysautonomia (FD), Duchenne Muscular Dystrophy (DMD), Adult Polyglucosan Body Disease (APBD) and others.

    G-INCPM-Special Seminar - Prof. Alan Russell, Director, Disruptive Health Technology Institute, Carnegie Mellon University, Pittsburgh, PA - Polymer-Based Protein Engineering

    Date:
    13
    Tuesday
    October
    2015
    Lecture / Seminar
    Time: 14:00-15:30
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Alan Russell
    Organizer: Department of Biomolecular Sciences
    Abstract: The application of enzymes to solve important problems has evolved over hundreds ...The application of enzymes to solve important problems has evolved over hundreds of years but has still not yet reached its fullest potential. The activity of enzymes in their natural state, in their ideal environment, and with their natural substrates is often much greater than needed ex vivo, thus driving intense research in activity enhancement. The inability to reach highly effective catalytic rates in harsh environments and against unnatural substrates has led to a number of elegant methods to modify enzyme structure and function. Lessons learned from molecular genetics, adaptation to organic solvents, immobilization, and conjugation with small molecules and polymers have greatly increased the activity of enzymes outside of their natural environments. For some applications, current protein engineering technologies have resulted in highly productive reagents. For many other applications, optimized solutions have been elusive. An evolution of our understanding of enzyme immobilization and polymer-protein conjugation has led to the emergence of polymer-based protein engineering (PBPE). We have developed and applied techniques that allow us to design and synthesize polymers directly from the protein surface. The process allows us to saturate conjugation sites, and by growing the polymers using atom transfer radical polymerization (ATRP), to control polymer size and structure. PBPE thus offers an attractive method to predictably modify and enhance enzyme structure and function. Using polymers that respond to stimuli such as temperature and pH, enzyme activity and stability can be predictably modified without a dependence on molecular biology. We have demonstrated that temperature responsive enzyme-polymer conjugates show increased stability while retaining bioactivity and substrate affinity. We are currently working on specific modifications of a number of proteins for a wide variety of uses such as oral therapeutics, biofuel cells, molecular sieves, proteomic applications, and agent decontamination.

    G-INCPM Special Seminar - Dr. Michael Angelo, MD, Instructor, Department of Pathology, Stanford University School of Medicine - High dimensional, immunohistochemical imaging in clinical tissue biopsies using multiplexed ion beam imaging (MIBI)

    Date:
    02
    Wednesday
    September
    2015
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Dr. Michael Angelo, MD
    Organizer: Department of Biomolecular Sciences
    Abstract: Multiplexed ion beam imaging (MIBI) is a novel approach to immunohistochemistry ...Multiplexed ion beam imaging (MIBI) is a novel approach to immunohistochemistry (IHC) that uses secondary ion mass spectrometry (SIMS) and antibodies labeled with elemental mass tags to visualize dozens of proteins simultaneously in a single tissue section. MIBI is compatible with standard formalin-fixed, paraffin-embedded (FFPE) tissue specimens, the most common sample type in clinical repositories worldwide, and can achieve single molecule sensitivity across a five log dynamic range at resolutions equivalent to brightfield microscopy. In recent work, MIBI was validated for imaging breast tumor tissue sections stained with clinically relevant metal-conjugated antibodies via side-by-side comparison with an FDA-approved quantitative image analysis platform. Since that time, my lab has validated over sixty antibodies and has constructed a 45-plex MIBI panel for characterizing phenotypic and epigenetic features of epithelial, stromal, and infiltrating immune cells in clinical breast tumor biopsies. Analogous approaches with metal conjugated oligonucleotides have also been used for multiplexed DNA and RNA ISH. Finally, to permit broader use of this method, we have designed and constructed novel instrumentation optimized for MIBI that is capable of super resolution imaging and one hundred fold faster sample throughput. Taken together, these tools are being used by lab to comprehensively enumerate immune cell populations in normal and neoplastic solid tissues, to develop clinical classifiers for predicting disease progression in pre-invasive cancer lesions, and to discover epigenetic drivers of epithelial to mesenchymal transition.

    G-INCPM Seminar - Dr. Eran Elinav, Dept. of Immunology, Weizmann Institute - "Host Microbiome Interactions in Health and Disease"

    Date:
    05
    Wednesday
    August
    2015
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Dr. Eran Elinav
    Organizer: Department of Biomolecular Sciences
    Abstract: The mammalian intestine contains trillions of microbes, a community that is domi ...The mammalian intestine contains trillions of microbes, a community that is dominated by members of the domain Bacteria but also includes members of Archaea, Eukarya, and viruses. The vast repertoire of this microbiome functions in ways that benefit the host. The mucosal immune system co-evolves with the microbiota beginning at birth, acquiring the capacity to tolerate components of the community while maintaining the capacity to respond to invading pathogens. The gut microbiota is shaped and regulated by multiple factors including our genomic composition, the local intestinal niche and multiple environmental factors including our nutritional repertoire and bio-geographical location. Moreover, it has been recently highlighted that dysregulation of these genetic or environmental factors leads to aberrant host-microbiome interactions, ultimately predisposing to pathologies ranging from chronic inflammation, obesity, the metabolic syndrome and even cancer. We have identified various possible mechanisms participating in the reciprocal regulation between the host and the intestinal microbial ecosystem, and demonstrate that disruption of these factors, in mice and humans, lead to dysbiosis and susceptibility to common multi-factorial disease. Understanding the molecular basis of host-microbiome interactions may lead to development of new microbiome-targeting treatments.

    PacBio SMRT Sequencing overview

    Date:
    29
    Wednesday
    July
    2015
    Lecture / Seminar
    Time: 09:30
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Amos Grundwag, Eisenberg Bros. Ltd.
    Organizer: Department of Molecular Genetics
    Abstract: Recent advancements in our understanding of biological complexity have propelled ...Recent advancements in our understanding of biological complexity have propelled the development of new tools. In the field of DNA and RNA sequencing, next-generation sequencers have dramatically increased productivity and provided novel insights into the structure and function of the genome. The PacBio RS II sequencing technology resolves single molecules in real time, allowing observation of structural and cell type variation not accessible with other technologies. These unique capabilities of the PacBio RS II system are ideally suited for a variety of applications, from De Novo assembly and targeted sequencing to detecting base modifications.

    G-INCPM-Seminar - Dr. Jacob Hanna, Dept. of Molecular Genetics, Weizmann Institute - "Molecular Mechanisms for Assembling and Resolving Distinct Pluripotent States"

    Date:
    08
    Wednesday
    July
    2015
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Dr. Jacob Hanna
    Organizer: Department of Biomolecular Sciences
    Abstract: The identity of somatic and pluripotent cells can be epigenetically reprogrammed ...The identity of somatic and pluripotent cells can be epigenetically reprogrammed and forced to adapt a new functional cell state by different methods and distinct combinations of exogenous factors. The aspiration to utilize such ex vivo reprogrammed pluripotent and somatic cells for therapeutic purposes necessitates understanding of the mechanisms of reprogramming and elucidating the extent of equivalence of the in vitro derived cells to their in vivo counterparts. In my presentation, I will present my group’s recent advances toward understanding these fundamental questions and further detail our ongoing efforts to generate developmentally unrestricted human naive pluripotent cells. I will conclude by highlighting new avenues for utilizing epigenetic reprogramming to naïve pluripotency for unraveling critical gene regulatory mechanisms acting during early mammalian development and highlighting prospects for new platforms for human disease and developmental modelling.

    GeneAnalytics and VarElect: NGS Gene-Set Flavors and Phenotype-Based Prioritization

    Date:
    23
    Tuesday
    June
    2015
    Lecture / Seminar
    Time: 11:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Gil Stelzer and Tsviya Olender
    Organizer: Life Sciences
    Abstract: We present GeneAnalytics, a novel and simple to use gene-set analysis website, a ...We present GeneAnalytics, a novel and simple to use gene-set analysis website, and VarElect, a phenotype interpretation tool which provides phenotype-dependent variant prioritization. GeneAnalytics was developed for biological researchers, allowing them to get an impression of the underlying biological processes occurring in their input gene-sets, e.g. a list of differentially expressed genes. GeneAnalytics searches for shared function and expression, without the need for a bioinformatician. Its expression-based analysis is powered by LifeMap Discovery®, which associates between genes and specific tissues, cells and diseases through a sophisticated analysis of manually curated and proprietary gene expression data of normal and diseased tissues and cells. Function-based analysis is based on shared diseases, pathways, Gene Ontology terms, and compounds. VarElect prioritizes a gene list in relation to phenotype/disease related keywords, via disease association, gene function, publications and various other data. VarElect also finds indirect associations, such as through shared pathways or interacting proteins. Both GeneAnalytics and VarElect leverage: GeneCards® – the human gene database, MalaCards – the human diseases database, PathCards- the biological pathways database and LifeMap Discovery® – the embryonic development and stem cells database. This seminar will describe both systems, as well as highlight case studies from the Department of Molecular Genetics that were elucidated by their insights.

    G-INCPM-Special Seminar - Dr. Shmulik Motola, Lab Manager, Massachusetts Institute of Technology (MIT), BioMicro Center Genomics Core, The MIT BioMicro Center - making the genomics work for you

    Date:
    17
    Wednesday
    June
    2015
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Dr. Shmulik Motola
    Organizer: Department of Biomolecular Sciences
    Abstract: The MIT BioMicro Center is an integrated genomics facility that provides both ex ...The MIT BioMicro Center is an integrated genomics facility that provides both expertise and equipment for systems biology. We offer researchers comprehensive genomics services, from experimental design to data analysis. Samples represent broad basic and translational research projects done at MIT. During the talk, I will discuss the challenges we face applying next generation sequencing techniques to research at MIT and how we overcome them.

    G-INCPM-Special Seminar - Prof. Young-Tae Chang, Laboratory Bioimaging Probe Development, Singapore Bioimaging Consortium - Universal Fluorescent Probe Platform for Almost Everything

    Date:
    15
    Monday
    June
    2015
    Lecture / Seminar
    Time: 15:00-16:00
    Location: Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Lecturer: Prof. Young-Tae Chang
    Organizer: Department of Biomolecular Sciences
    Abstract: The conventional bioprobe design has been carried out by so-called hypothesis-dr ...The conventional bioprobe design has been carried out by so-called hypothesis-driven approach. The basic assumption of hypothesis-driven approach is that the scientist “knows the target” in advance, and then design the recognition motif for it. An alternative approach is diversity-driven approach, in which a broad range of fluorescence molecules in a library format are constructed by combinatorial chemistry, as a tool box for unbiased screening. Among several diversity sources, “Diversity Oriented Fluorescence Library Approach (DOFLA)” using fluorophore core with diverse recognition motives around has been the most fruitful in novel bioprobe generations. Using DOFLA, various colorful sensors for many different analytes and bioimaing probes from stem cells to neuron cells will be demonstrated. Whole body animal imaging will also be presented using NIR range of probes.

    ICSG2015 - Deep Sequencing Meets Structural Biology

    Date:
    07
    Sunday
    June
    2015
    -
    11
    Thursday
    June
    2015
    Conference
    Time: 00:00
    Location: David Lopatie Conference Centre

    G-INCPM-Special Seminar - Dr. Aya Soffer, Director, Information Management Analytics, IBM Research - Cognitive Systems – A New Era of Computing

    Date:
    13
    Wednesday
    May
    2015
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Michael and Anna Wix Auditorium
    Lecturer: Dr. Aya Soffer
    Organizer: Department of Biomolecular Sciences
    Details: The Jeopardy winning Watson system that lies at the intersection of many fields - machine learning, predictive analytics, natural language processing - heralds the dawn of an exciting new era in computing: the cognitive systems era. Trends in Mobile, Social and the Internet of Things are each creating exponentially growing waves of Big Data. What we have learned from Watson and learning systems in general is that Big Data is just a starting point for getting into a new kind of computing in which systems learn, make inferences, create hypotheses and penetrate complexity. This talk will describe the underlying technologies that are needed to enable the new era of cognitive systems, as well as demonstrate how these systems can learn and interact to provide expert assistance to scientists, engineers, lawyers, and other professionals in a fraction of the time it now takes.

    Cancer Meets Epitranscriptomics

    Date:
    04
    Monday
    May
    2015
    Lecture / Seminar
    Time: 14:00
    Location: Max and Lillian Candiotty Building
    Lecturer: PROF. GIDI RECHAVI
    Organizer: Department of Biological Regulation
    Abstract: In the last decade advances in Next Generation Sequencing and bioinformatics ena ...In the last decade advances in Next Generation Sequencing and bioinformatics enabled the unraveling of global RNA modifications and editing. The evolving field of epitranscriptomics proved to be important in cell fate decisions, normal development and disease. The lecture will deal with A to I editing-based mechanisms relevant to cancer and with the emerging role of m6A methylation in the precise regulation of early embryonic development.

    Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq

    Date:
    28
    Tuesday
    April
    2015
    Lecture / Seminar
    Time: 12:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Amit Zeisel
    Organizer: Department of Neurobiology
    Abstract: The mammalian cerebral cortex supports cognitive functions such as sensorimotor ...The mammalian cerebral cortex supports cognitive functions such as sensorimotor integration, memory, and social behaviors. Normal brain function relies on a diverse set of differentiated cell types, including neurons, glia, and vasculature. Here, we have used large-scale single-cell RNA sequencing (RNA-seq) to classify cells in the mouse somatosensory cortex and hippocampal CA1 region. We found 47 molecularly distinct subclasses, comprising all known major cell types in the cortex. We identified numerous marker genes, which allowed alignment with known cell types, morphology, and location.

    G-INCPM - Special Guest Seminar - Prof. Ray Cooper, Dept. Applied Biology & Chemical Technology, The Hong Kong Polytechnic Univ. - Chinese and Botanical Medicines: Myth or Treasure?

    Date:
    15
    Wednesday
    April
    2015
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Michael and Anna Wix Auditorium
    Lecturer:
    Organizer: Department of Biomolecular Sciences
    Abstract: There is a need to improve and promote the scientific inquiry on the study and u ...There is a need to improve and promote the scientific inquiry on the study and use of botanicals, natural products and Chinese Medicine, in order to secure global acceptance. Although there is an enormous history of use of Chinese medicines a better understanding of these preparations and formulae within the scientific and international community is needed. The aim is to present case studies on select botanicals and natural products to provide scientific data that could substantiate the health claims. One example is the inhibition of ENOX2 (tNOX), a molecular target to examine anticancer activity of green tea catechins. The relation between green tea catechins and cell protection through a cell surface protein, ENOX2 has been identified. When the ENOX2 of cells is inhibited, the cells fail to enlarge after division, cease to divide, and after a few days undergo apoptosis. To date, EGCg in green tea is the most effective polyphenol ENOX2 blocker found without any adverse effects on normal cells. Synergistic combinations of green tea concentrate and powdered Capsicum reduces oxidative stress as an approach to elimination of malignant cells in both cancer (HeLa) and non-cancer (MCF-10A) cells. Some preliminary data on green tea and other examples of well-known botanical medicines descibed in Chinese folklore will be presented.

    G-INCPM-Special Seminar - lecture will be in Hebrew - Dr. Ori Inbar, Researcher at Evogene & Chairperson of the Israeli CF Foundation - Kalydeco - breakthrough personalized medicine for Cystic Fibrosis (CF)

    Date:
    04
    Wednesday
    March
    2015
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Michael and Anna Wix Auditorium
    Lecturer:
    Organizer: Department of Biomolecular Sciences
    Abstract: Cystic Fibrosis (CF) is the most frequent life threatening genetic disorder in t ...Cystic Fibrosis (CF) is the most frequent life threatening genetic disorder in the western world. The disease is caused by mutations in the CFTR genes that encode a chloride membrane channel protein that is expressed in epithelial cells. Malfunction of this protein causes a multi system disorder: lungs, pancreas, intestine, liver, bones, sweat glands and male reproductive system. Two years ago the FDA approved Kalydeco, the first personalized drug which is mutation specific: for CF patients that have at least one copy of the mutation G551D. Binding of Kalydeco to the impaired CFTR protein restores its functionality. The following will be reviewed: CF-genetic basis, prognosis, treatments and genetic tests in Israel and Kalydeco - mode of action, clinical effect on patients, future development and its Israeli angle.

    Connectomes on Demand?

    Date:
    24
    Tuesday
    February
    2015
    Lecture / Seminar
    Time: 12:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Nir Shavit
    Organizer: Department of Neurobiology
    Abstract: Genomic sequencing has become a standard research tool in biology, going within ...Genomic sequencing has become a standard research tool in biology, going within 20 years from a high-risk global project into clinical use. Connectomics, the generation (at this point through electron microscopy), of a connectivity graph for a volume of neural tissue, is still in its infancy. This talk will survey the road ahead, the various technical and computational problems we face, and the joint MIT/Harvard effort to devise an automated pipeline that will allow researchers to have connectomes generated on demand.

    G-INCPM - Special Guest Seminar - Dr. Irit Paz, Global Sales Manager, Takara Clontech, France - SMARTer Solutions for Next Gen Sequencing (Danyel Biotech)

    Date:
    23
    Monday
    February
    2015
    Lecture / Seminar
    Time: 13:30-14:30
    Location: Camelia Botnar Building
    Lecturer:
    Organizer: Department of Biomolecular Sciences
    Abstract: Next-generation sequencing (NGS) has increased our understanding of biology by e ...Next-generation sequencing (NGS) has increased our understanding of biology by enabling highly sensitive RNA expression analysis across a wide dynamic range. As NGS applications continue to grow, so does the need for more powerful tools to work with less-than-ideal samples. As the core of the SMARTer kits for transcriptome analysis, Clontech’s patented SMART® technology utilizes the template switching activity of reverse transcriptase to enable researchers to analyze their most challenging samples, such as single cells, low-input RNA, noncoding RNA, and RNA from degraded samples. In particular, single-cell RNA-seq is one of the more difficult, and fastest growing, applications of NGS. The high sensitivity and dT-primed protocol of the SMARTer Ultra Low family has made these kits the industry standard for single-cell analysis. Applications of SMART technology are constantly expanding and now include a novel, ligation-free method for generating ChIP (chromatin immunoprecipitation) sequencing libraries. The purpose of this seminar is to take a deeper look into the new technologies being developed for single-cell RNA-seq and other sensitive NGS applications.

    G-INCPM special guest seminar - More physiologically relevant cellular models compatible with High Content Analysis

    Date:
    14
    Wednesday
    January
    2015
    Lecture / Seminar
    Time: 10:00-11:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Sebastien Degot
    Organizer: Department of Biomolecular Sciences
    Abstract: iPS-derived cells, primary cells and even immortal cell lines grown in standard ...iPS-derived cells, primary cells and even immortal cell lines grown in standard 2D culture conditions are valuable tools for basic research, drug discovery and drug safety. However, the selection and detection of active compounds based on such in vitro models has so far been of limited value. Two major limitations could explain this phenomenon. First, monolayer cells do not reflect properly native tissue morphology and second, available relevant readouts are limited. Consequently, there is increasing awareness that the development of cellular models with higher physiological relevance coupled to more informative readouts are prerequisite to improving cell-based assays. In this context, we have developed several models based on micropattern technology as well as dedicated image analysis that address individually or simultaneously the bottlenecks cited above. Examples of the different applications will be presented with a specific highlight on multi-cellular models where several key cellular features demonstrated higher maturation levels on micropattern compared to conventional 2D cultures. The apparent resuscitation and/or stabilization of cellular functions allowed implementation of innovative readouts that are more relevant to the physiology of the systems, using imaging and High Content Analysis. Furthermore, the micropatterned organ models consist of multiple homogeneous uniform structures per well, facilitating segmentation and identification of features such as width of myotubes for higher throughput automated image analysis. Alltogether, our work suggests that control of cell adhesion and cell-cell interactions promotes multi-cellular self-organization and enhances overall function, opening up access to novel cellular readouts. Micropatterns offer an opportunity to improve upon 2D cultures of several cellular models, even for cells that are the closest representatives of in vivo functionalities, further upgrading their usefulness for screening and mechanistic investigation of candidate drugs or signaling pathways.

    A novel approach to the study of neurodegenerative diseases:In vivo screening within the mouse CNS identifies modulators of Huntington disease

    Date:
    30
    Tuesday
    December
    2014
    Lecture / Seminar
    Time: 12:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Reut Shema
    Organizer: Department of Neurobiology
    Abstract: Understanding the molecular basis of neurodegenerative diseases (NDDs), and how ...Understanding the molecular basis of neurodegenerative diseases (NDDs), and how they interact with the aging process, is one of the greatest challenges in neuroscience. As the most common NDDs, including Alzheimer’s, Parkinson’s, and Huntington’s diseases remain essentially without a cure, the search for therapeutic targets becomes imperative. We have developed a novel platform for the study of NDDs, utilizing the disease-relevant cellular populations in their natural environment. For these screens, which we term SLIC (Synthetic Lethal In the Central nervous system), pooled libraries of lentivirus for knock-down, knock-out, or over-expression of all known genes in the genome are injected into the relevant disease regions in the mouse brain, with one barcoded virus infecting one cell. Comparison, by genomic sequencing, of lentiviruses that are retrieved from wild-type animals, but not from disease model littermates, after various times of incubation in the mouse brain, reveals target genes that function as enhancers of toxicity specific to the disease-associated mutation. We have implemented SLIC for the study of Huntington’s disease, which is the most common inherited NDD caused by abnormal CAG expansion in the Huntingtin gene. We identified the age-regulated glutathione peroxidase 6 (Gpx6) as a modulator of mutant huntingtin toxicity, and show that overexpression of Gpx6 can dramatically alleviate both behavioral and molecular phenotypes associated with a mouse model of Huntington’s disease. SLIC can, in principle, be used in the study of any neurodegenerative disease for which a mouse model exists, promising to reveal modulators of neurodegenerative disease in an unbiased fashion, akin to screens in simpler model organisms.

    Fine scale diversity in microbial populations and its impact on community resilience

    Date:
    16
    Tuesday
    December
    2014
    Lecture / Seminar
    Time: 11:15
    Location: Ullmann Building of Life Sciences
    Lecturer: Dr. Itai Sharon
    Organizer: Department of Plant and Environmental Sciences
    Abstract: Microbial communities often consist of many closely related strains or species t ...Microbial communities often consist of many closely related strains or species that exhibit small genomic differences compared with one another. These variations are thought to play crucial roles in maintaining community resilience and in the evolution of new species. Multiple examples now exist for the impact of species and strain variations on community outcome and its environment as in the cases of methicillin resistant Staphylococcus aureus (MRSA) and pathogenic Escherichia coli. However, very little is known about the scale and dynamics of these variations in natural environments. In this talk I will discuss species- and strain-variations in two distinct environments: the simple developing microbial community in the gut of newborns and the complex microbial communities in terrestrial sediments. Using new methods for the recovery of dozens of genomes from environmental DNA sequencing (metagenomics) data and an analysis of synthetic long reads we were able to thoroughly describe systems of species- and strain- variations in both environments. These include strain-specific phage predation during infant gut colonization, and also complex populations of dozens of species and strains in terrestrial sediments. The implications of our findings as well as future directions will also be presented.

    G-INCPM special guest seminar - Inflammatory links between obesity and type 2 diabetes

    Date:
    04
    Thursday
    December
    2014
    Lecture / Seminar
    Time: 10:00-11:30
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Dr. Alan Saltiel
    Organizer: Department of Biomolecular Sciences
    Abstract: Obesity is associated with chronic low-grade inflammation that negatively impact ...Obesity is associated with chronic low-grade inflammation that negatively impacts insulin sensitivity. High fat diet can increase NFB activation in mice, which leads to a sustained elevation in levels of the non-canonical IKKs, IB kinase  (IKK) and TBK1, in liver, adipocytes and adipose tissue macrophages. We explore the role of these enzymes by gene knockout and inhibitor studies. These data suggest that IKKand TBK1 play an important role in chronic inflammation in liver and fat, hepatic steatosis and whole-body insulin resistance. Blockade of the activity of these two kinases produces increased energy expenditure and thermogenesis, along with improved insulin resistance and fatty liver. We will discuss the role of inflammation and the NFkB pathway in the generation of insulin resistance and persistent obesity in metabolic disease.

    Fluidigm Technologies For Single-Cell Genomics and Proteomics

    Date:
    12
    Wednesday
    November
    2014
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Ullmann Building of Life Sciences
    Lecturer: Amy Hamilton
    Organizer: Department of Life Sciences Core Facilities
    Abstract: Introducing new applications and workflow enhancements for the C1 Single-Cell Au ...Introducing new applications and workflow enhancements for the C1 Single-Cell Auto Prep System. Methods for optimum cell preparation and cell qualification for the C1™ Single-Cell Auto Prep System. Understanding biological heterogeneity with CyTOF-2 Mass Cytometer.