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

Date:
21
Monday
February
2022
-
23
Wednesday
February
2022
Conference
Time: 08:00
Location: David Lopatie Conference Centre

    Past

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    Plant immune system activation is necessary for efficient interaction with auxin secreting beneficial bacteria

    Date:
    12
    Tuesday
    October
    2021
    Lecture / Seminar
    Time: 15:00-16:00
    Title: Guest Seminar via Zoom
    Location: https://weizmann.zoom.us/j/97684910013?pwd=ai9wWUZQNWdVRVU2Y3laaUlWRmdwUT09 Password 973838
    Lecturer: Dr. Elhanan Tzipilevich
    Organizer: Department of Plant and Environmental Sciences
    Details: Host: Prof. Asaph Aharoni
    Abstract: Plants continuously monitor the presence of microorganisms through their immune ... Read more Plants continuously monitor the presence of microorganisms through their immune system to establish an adaptive response. Unlike immune recognition of pathogenic bacteria, mechanisms by which beneficial bacteria interact with the plant immune system are not well understood. Analysis of colonization of Arabidopsis thaliana by auxin producing beneficial bacteria revealed that activating the plant immune system is necessary for efficient bacterial colonization and auxin secretion. A feedback loop is established in which bacterial colonization triggers an immune reaction and production of reactive oxygen species, which, in turn, stimulate auxin production by the bacteria. Auxin promotes bacterial survival and efficient root colonization, allowing the bacteria to compete with other members of the root microbial community and inhibit fungal infection, promoting plant health.
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    Deciphering the role of brain- resident and infiltrating myeloid cells in Alzheimer’s disease

    Date:
    19
    Sunday
    September
    2021
    Lecture / Seminar
    Time: 14:00-15:30
    Lecturer: Raz Dvir-Szternfeld (PhD Thesis Defense)
    Organizer: Department of Brain Sciences
    Details: Zoom link to join: https://weizmann.zoom.us/j/97303536627?pwd=YXFQZUozb1hhMS9xY ... Read more Zoom link to join: https://weizmann.zoom.us/j/97303536627?pwd=YXFQZUozb1hhMS9xY3BzOFJPZU1Vdz09 Meeting ID: 973 0353 6627 Password: 503277
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    Abstract: Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, which i ... Read more Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, which is the most common cause of dementia. Among the key hallmarks of AD are neurofibrillary tangles, abnormal amyloid beta (A) aggregation, neuroinflammation and neuronal loss; altogether manifested in progressive cognitive decline. Numerous attempts were made to arrest or slow disease progression by directly targeting these factors, with a limited successes in having a meaningful effect on cognition. In the recent years, the focus of AD research has been extended towards exploring the local and systemic immune response. Yet, the role of the two main myeloid populations, the central nerve system (CNS) resident immune cells, microglia and blood-borne monocyte-derived macrophages (MDM) remain unclear. In my PhD, together with members of the teams, using behavioral, immunological, biochemical and single-cell resolution molecular techniques, we deciphered the distinct role of microglia and MDM in transgenic mouse models of AD pathology. Using single cell RNA sequencing (scRNA-seq) in 5xFAD amyloidosis mouse model, we have identified a new state of microglia, which we named disease associated microglia (DAM) that were found in close proximity to A plaques. The full activation of these cells was found to be dependent on Triggering receptor expressed on myeloid cells 2 (TREM2), a well-known risk factor in late onset AD. To get an insight to the role of MDM relative to microglia, we used an experimental paradigm of boosting the systemic immunity by modestly blocking the inhibitory immune checkpoint pathway, PD-1/PD-L1, which was previously shown to be beneficial in ameliorating AD in 5xFAD mice, via facilitating homing of MDM to the brain. We found that the same treatment is efficient also in mouse model of tauopathy and that the MDM homing to the brain following the treatment expressed a unique set of scavenger molecules, including macrophage scavenger receptor 1 (MSR1). We found that MDM expressing MSR1 are essential for the disease modification. Using the same immune-modulatory treatment in a mouse model deficient in TREM2 (Trem2-/-5xFAD) and thus in DAM, allowed us to distinguish between the contribution to the disease modification of MDM and DAM. We found, that MDM display a Trem2-independent role in the cognitive improvement. In both Trem2-/-5xFAD and Trem2+/+5xFAD mice the treatment effect on behavior was accompanied by a reduction in the levels of hippocampal water-soluble Aβ1-42, a fraction of A that contains toxic oligomers. In Trem2+/+5xFAD mice, the same treatment seemed to activate additional Trem2-dependent mechanism, that could involve facilitation of removal of Aβ plaques by DAM or by other TREM2-expressing microglia. Collectively, our finding demonstrates the distinct role of activated microglia and MDM in therapeutic mechanism of AD pathology. They also support the approach of empowering the immune system to facilitate MDM mobilization as a common mechanism for treating AD, regardless of primary disease etiology and TREM2 genetic polymorphism.
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    Conservation of TIR immune signaling in bacteria and plants

    Date:
    06
    Tuesday
    July
    2021
    Lecture / Seminar
    Time: 11:30-12:30
    Title: Guest Seminar via Zoom
    Location: https://weizmann.zoom.us/j/94920680518?pwd=MDhOVUZsQWRaMGZSYndIME5lZGtRdz09 Password 151190
    Lecturer: Gal Ofir
    Organizer: Department of Plant and Environmental Sciences
    Details: Host: Prof. Avraham Levy

    IMM Guest seminar- Dr. Michael Brusilovsky, will lecture on "Unlocking the mechanisms of innate-immune sensory systems."

    Date:
    03
    Monday
    May
    2021
    Lecture / Seminar
    Time: 13:00-14:00
    Lecturer: Dr. Michael Brusilovsky
    Organizer: Department of Immunology
    Details: the lecture will take place via ZOOM: https://weizmann.zoom.us/j/91805575177?pw ... Read more the lecture will take place via ZOOM: https://weizmann.zoom.us/j/91805575177?pwd=MWtRSy9KTmp3MXBNUnlHU2g3dzY4QT09 password: 181113
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    Rapid mass spectrometry investigation of overproduced proteins from crude samples

    Date:
    22
    Monday
    February
    2021
    Colloquium
    Time: 11:00-12:00
    Location: https://weizmann.zoom.us/j/98063488104?pwd=N3VqTC9sU1A4RHVDZ1dhOGVxbU1iUT09
    Lecturer: Prof. Michal Sharon
    Organizer: Faculty of Chemistry
    Abstract: Analysis of intact proteins by native mass spectrometry has emerged as a powerfu ... Read more Analysis of intact proteins by native mass spectrometry has emerged as a powerful tool for obtaining insight into subunit diversity, post-translational modifications, stoichiometry, structural arrangement, stability, and overall architecture. Typically, such an analysis is performed following protein purification procedures, which are time consuming, costly, and labor intensive. As this technology continues to move forward, advances in sample handling and instrumentation have enabled the investigation of intact proteins in crude samples, offering rapid analysis and improved conservation of the biological context. This emerging approach is expected to impact many scientific fields, including biotechnology, pharmaceuticals, and clinical sciences. In my talk I will discuss the information that can be retrieved by such experiments as well as the applicability of the method by presenting the characterization of engineered proteins, drug binding, antibody specificity and protein-protein interactions.
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    FIXING A BROKEN IMMUNE SYSTEM- Immunology Symposium in Honor of PROF. MICHAEL SELA

    Date:
    14
    Monday
    December
    2020
    Conference
    Time: 09:30-12:30
    Location: Zoom Meeting
    Organizer: Department of Immunology
    Details: מכונות ביולוגיות, הנדסת-ננו וחיישנים ביו-מו ... Read more מכונות ביולוגיות, הנדסת-ננו וחיישנים ביו-מולקולריים הם חידושים שנועדו להצעיד אותנו אל עתיד הרפואה, התחבורה, התקשורת והעיצוב.
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    Host Pathogen Club, December 7th at 12:15 PM

    Date:
    07
    Monday
    December
    2020
    Lecture / Seminar
    Time: 12:15
    Title: "?How has African Salmonella become so dangerous"
    Lecturer: Prof. Jay Hinton
    Organizer: Life Sciences
    Details: zoom link: https://weizmann.zoom.us/j/93489345354?pwd=cHdtRUxvZ1VXanU5UndLd1NEM ... Read more zoom link: https://weizmann.zoom.us/j/93489345354?pwd=cHdtRUxvZ1VXanU5UndLd1NEMVVIZz09 Password: 047542
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    Cancer evolution, immune evasion and metastasis

    Date:
    19
    Thursday
    November
    2020
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Charles Swanton MD PhD FMedSci FRS
    Organizer: Dwek Institute for Cancer Therapy Research
    Details: https://weizmann.zoom.us/j/5065402023?pwd=a3Z6KzRCU0xJaUFoM2Y5emZwZm1oZz09

    Love thy neighbor - unraveling the tumor microenvironment by multiplexed imaging

    Date:
    17
    Tuesday
    November
    2020
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Dr. Leeat Keren
    Organizer: Department of Biomolecular Sciences
    Abstract: Tumors are spatially organized ecosystems that are comprised of distinct cell ty ... Read more Tumors are spatially organized ecosystems that are comprised of distinct cell types, each of which can assume a variety of phenotypes defined by coexpression of multiple proteins. To underscore this complexity, and move beyond single cells to multicellular interactions, it is essential to interrogate cellular expression patterns within their native context in the tissue. We have pioneered MIBI-TOF (Multiplexed Ion Beam Imaging by Time of Flight), a platform that enables simultaneous imaging of forty proteins within intact tissue sections at subcellular resolution. In this talk, I will describe our application of multiplexed imaging to study the tumor immune microenvironment in triple negative breast cancer. Our work reveals archetypical organizations, linking molecular expression patterns, cell composition and histology, which are predictive of patient survival.
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    Immune therapy for Alzheimer’s disease and Dementia: From the bench to the bedside

    Date:
    03
    Tuesday
    November
    2020
    Lecture / Seminar
    Time: 12:30
    Lecturer: Prof. Michal Schwartz
    Organizer: Department of Brain Sciences
    Details: Seminar on Zoom https://weizmann.zoom.us/j/93371812582?pwd=VEpIZHB1U0QwMWNhY05F ... Read more Seminar on Zoom https://weizmann.zoom.us/j/93371812582?pwd=VEpIZHB1U0QwMWNhY05FWWtZcVZnQT09 Meeting ID: 933 7181 2582 Password: 610265
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    Abstract: With increased life expectancy, the incidence of patients suffering from Alzheim ... Read more With increased life expectancy, the incidence of patients suffering from Alzheimer’s disease (AD) and dementia has been steadily increasing. Currently, there is not a single treatment that can change the diseases course. Our team, over more than two decades, has demonstrated that the brain needs support from the immune system for its life-long functional plasticity and repair. Furthermore, using immunological and immunogenomic tools, we demonstrated that in AD, the immune system dysfunctions and perpetuates the pathology. Based on these observations and numerous others, we proposed that boosting the systemic immune system might facilitate mobilization of immune cells to help the brain. We found that the optimal way to activate such a reparative immune response is by reducing the restraints on the immune system, by blocking the PD-1/PD-L1 inhibitory immune checkpoint pathway. This therapy facilitates translocation of phagocytic cells to the brain; based on their transcriptomic profile, we demonstrated that these cells express molecules that can uniquely remove the toxic forms of misfolded proteins plaques, dead cells, and cell debris, and can thereby rescue synapses, change the disease course and improve brain function. Overall, our results indicate that targeting systemic and local immune cells rather than brain-specific disease-escalating factors provides a multi-dimensional disease-modifying therapy for AD and dementia, regardless of the primary disease etiology. Our approach is under an expedited development process towards clinical trial.
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    Reversing personalized medicine

    Date:
    10
    Thursday
    September
    2020
    Lecture / Seminar
    Time: 13:30-14:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Gal Markel
    Organizer: Department of Biological Regulation
    Details: the link for the lecture's zoom room https://weizmann.zoom.us/j/5065402023?pwd= ... Read more the link for the lecture's zoom room https://weizmann.zoom.us/j/5065402023?pwd=a3Z6KzRCU0xJaUFoM2Y5emZwZm1oZz09
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    Abstract: Personalized medicine in oncology is focused on fitting drugs to the appropriat ... Read more Personalized medicine in oncology is focused on fitting drugs to the appropriate patients, mainly by identifying unique mutations in tumor genomics and development of highly selective drugs. The main challenge is that the relevant populations grow smaller, while development costs are constant, leading to significant reduction in effective drug development. The immune system provides personalized anti cancer response, and immune checkpoint inhibitors enable decent responses over a wide array of tumors. The outstanding challenge is that efficacy is observed in less than a third of the patients. Here we explore strategies to alter the patient in a way that will enable standard of care immunotherapy to exert its full potential, i.e. fitting the patients to the existing immunotherapeutic medications.
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    The power of ONE: Immunology in the age of single cell genomics

    Date:
    02
    Thursday
    July
    2020
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Ido Amit
    Organizer: Dwek Institute for Cancer Therapy Research

    Departmental Seminar by Aya Shkedy

    Date:
    14
    Sunday
    June
    2020
    Lecture / Seminar
    Time: 13:00-14:00
    Title: "The intricate host-pathogen interactions: Protection from trypanosomes by the ApoL1 heritable mutations turns on specific cell death mechanisms"
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Organizer: Department of Molecular Genetics
    Details: Seminar via zoom, to join: https://weizmann.zoom.us/j/96661412610

    SARAF as a regulator of store-operated calcium entry

    Date:
    09
    Tuesday
    June
    2020
    Lecture / Seminar
    Time: 10:00-10:45
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Anna Meshcheriakova
    Organizer: Department of Biomolecular Sciences
    Abstract: Calcium signaling serves as a means of regulation of virtually all processes in ... Read more Calcium signaling serves as a means of regulation of virtually all processes in a cell throughout the life of an organism, from fertilization to death. One of the multiple aspects of calcium signaling is store-operated calcium entry (SOCE) that has been raising a great interest in the last 30 years. Disregarded first for its allegedly negligible effect on calcium changes inside a cell, it is being reconsidered nowadays as a ubiquitous phenomenon regulating pivotal processes, such as transcription, immune response and others. As other pathways of calcium signaling, SOCE is regulated by multiple proteins, required for adjusting calcium levels to current cellular needs. Among them is SARAF, a protein that has been shown to negatively regulate SOCE, thus preventing calcium excess inside a cell. I will try to elaborate on my attempts to decipher the mysterious mechanism of its regulation.
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    Computational design of enzyme repertoires

    Date:
    26
    Tuesday
    May
    2020
    Lecture / Seminar
    Time: 10:00-10:45
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Rosalie Lipsh-Sokolik
    Organizer: Department of Biomolecular Sciences
    Abstract: Antibodies are produced to target any antigen using a finite set of gene fragm ... Read more Antibodies are produced to target any antigen using a finite set of gene fragments generating a huge diversity (>1010) distinct structures. In contrast, we are unaware of a system that can produce analogous diversity in enzymes. Inspired by antibody repertoires, I have developed the first strategy to design, synthesise, and experimentally test repertoires comprising millions of enzymes. Using evolution-guided atomistic design simulations, I designed thousands of protein fragments that exhibited high structure and sequence diversity, including within the active-site pocket, which can be genetically assembled into full-length enzymes. I also developed an ML-based algorithm to select a subset of the designed fragments that would give rise to stable and active proteins. Applied to a family of xylanases (sophisticated enzymes which are critical in biomass degradation) I designed a repertoire comprising a million enzymes at a cost of 0.3¢ per enzyme. Screening with an activity-based probe revealed thousands of functional xylanases based on nearly 1,000 unique backbones. Advanced machine-learning methods uncovered important elements that discriminate active from inactive designs, enabling us to design even more effective enzyme repertoires targeting, in principle, any desired substrate. Thus, enzyme repertoire design will enable a new generation of highly efficient and selective enzymes, while teaching us essential rules in biomolecular design.
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    Resistance Mechanisms of Salmonella Typhimurium to Antimicrobial Peptides

    Date:
    19
    Tuesday
    May
    2020
    Lecture / Seminar
    Time: 10:00-10:45
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Gal Kapach
    Organizer: Department of Biomolecular Sciences
    Abstract: Bacterial resistance to antibiotics is a major concern worldwide, leading to an ... Read more Bacterial resistance to antibiotics is a major concern worldwide, leading to an extensive search for alternative drugs. Promising candidates are antimicrobial peptides, innate immunity molecules, which were shown to be highly efficient against multidrug resistant bacteria. Therefore, it is essential to study bacterial resistance mechanisms against them. In Salmonella Typhimurium (S.Typhimurium), a pathogenic bacterium that causes inflammation of the gastrointestinal tract, resistance to antimicrobial peptide is mainly mediated by surface modifications. These reduce the molecular interactions between the bacterial surface and the peptides. Searching for new resistance mechanisms to antimicrobial peptides, we revealed two novel strategies that evolved in a S. Typhimurium resistant line. One involves mutations in the AcrAB-TolC efflux pump and the second is acquired by the loss of the periplasmic chaperone Skp. Our data provide a deeper understanding on the role of the AcrAB-TolC system and Skp in S. Typhimurium.
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    POSTPONED: Frontiers in Immunology (EFIS onTour)

    Date:
    17
    Sunday
    May
    2020
    Conference
    Time: 08:00
    Location: David Lopatie Conference Centre
    Organizer: Department of Immunology

    Chemistry Colloquium

    Date:
    11
    Monday
    May
    2020
    Colloquium
    Time: 11:00-12:15
    Title: The Macromolecular Structure of Mucus, Our Bodies’ First Line of Defense Against Pathogens
    Location: https://weizmann.zoom.us/j/92049901272
    Lecturer: Prof. Debbie Fass
    Organizer: Faculty of Chemistry
    Abstract: Respiratory viruses such as coronavirus spread from person to person through dro ... Read more Respiratory viruses such as coronavirus spread from person to person through droplets of saliva or mucus. Face masks decrease the dissemination of such droplets and thereby minimize viral propagation from someone who may be contagious. Mucus did not evolve, though, to help pathogens spread. Quite the opposite. Mucus arose early in the evolution of multicellular animals to exclude undesirable bacteria from body tissues, a primitive type of immunity. The cooperation between cilia* and mucus also helped prevent aquatic organisms from being smothered by sediments and enabled them to clean or collect particulate matter from their exteriors. Producing mucus was likely a prerequisite for evolution of the gut and of the types of respiratory organs necessary for terrestrial life. Today, mucus protects the large, exposed interior surfaces of our respiratory and gastrointestinal tracts from bacteria, viruses, parasites, and chemical/physical hazards. But what material is mucus? Mucus is a hydrogel made of heavily glycosylated protein molecules called “mucins,” each of which is nearly 3 megadaltons in size. Individual giant mucin molecules are disulfide bonded to one another, generating an extended mesh. Using cryo-electron microscopy and X-ray crystallography, we have discovered the three-dimensional structure of mucins and gained insight into the mechanism by which they assemble step-wise into hydrogels. ______________________________________________________ * cell-surface, rope-like structures that beat in coordinated waves
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    Resistance Mechanisms of Salmonella Typhimurium to Antimicrobial Peptides

    Date:
    17
    Tuesday
    March
    2020
    Lecture / Seminar
    Time: 10:00-10:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Gal Kapach
    Organizer: Department of Biomolecular Sciences
    Abstract: Bacterial resistance to antibiotics is a major concern worldwide, leading to an ... Read more Bacterial resistance to antibiotics is a major concern worldwide, leading to an extensive search for alternative drugs. Promising candidates are antimicrobial peptides, innate immunity molecules, which were shown to be highly efficient against multidrug resistant bacteria. Therefore, it is essential to study bacterial resistance mechanisms against them. In Salmonella Typhimurium (S.Typhimurium), a pathogenic bacterium that causes inflammation of the gastrointestinal tract, resistance to antimicrobial peptide is mainly mediated by surface modifications. These reduce the molecular interactions between the bacterial surface and the peptides. Searching for new resistance mechanisms to antimicrobial peptides, we revealed two novel strategies that evolved in a S. Typhimurium resistant line. One involves mutations in the AcrAB-TolC efflux pump and the second is acquired by the loss of the periplasmic chaperone Skp. Our data provide a deeper understanding on the role of the AcrAB-TolC system and Skp in S. Typhimurium.
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    Azrieli Institute for Systems Biology

    Date:
    04
    Wednesday
    March
    2020
    Lecture / Seminar
    Time: 14:00-15:00
    Title: “Does host-pathogen coevolution explain extraordinary genetic diversity”
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Prof. Dieter Ebert
    Organizer: Azrieli Institute for Systems Biology

    Uncovering a ‘Quorum Sensing-Like’ Mechanism of Malaria Parasites

    Date:
    03
    Tuesday
    March
    2020
    Lecture / Seminar
    Time: 10:30-11:00
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Anna Rivkin
    Organizer: Department of Biomolecular Sciences
    Abstract: The ability of pathogens to sense and respond to changes enables them to adapt a ... Read more The ability of pathogens to sense and respond to changes enables them to adapt and survive in hostile environments. In particular, microbes have developed a mechanism called quorum sensing, in which they produce, detect and respond to small, secreted molecules. One of the deadliest pathogens in humans is the parasite Plasmodium falciparum (Pf), the infectious agent of the malaria disease, accounting for the death of about half a million people annually. Here, we reveal that these parasites employ a quorum sensing-like mechanism to respond to their own density and coordinate their asexual growth during the blood stage of their life cycle. Namely, Pf parasites govern their own cell density by secreting active molecule(s). Using a combination of biochemical techniques, we chemically characterized the active fraction (autoinducer-like molecule) and revealed it to be a hydrophilic, positively charged molecule of a size ranging from 100Da to 4,000Da. Further purification using high-pressure liquid chromatography (HPLC) enabled the putative detection of two metabolites. Our finding suggests that malaria parasites signal each other to coordinate their asexual growth pattern is a previously unrecognized survival strategy. Identification and further investigation of the active secreted molecule can potentially lead to the development of anti-malaria drugs.
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    Special Guest Seminar with Prof. Detlef Wiegel

    Date:
    12
    Wednesday
    February
    2020
    Lecture / Seminar
    Time: 11:30-12:30
    Title: “Epistasis; the spice of life (and evolution): Lessons from the plant immune system”
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Detlef Wiegel
    Organizer: Department of Molecular Genetics
    Details: My group is addressing fundamental questions in evolutionary biology, using both ... Read more My group is addressing fundamental questions in evolutionary biology, using both genome- and phenotype-first approaches. A few years ago, we discovered that Arabidopsis thaliana is a great model for the study of hybrid necrosis. This widespread syndrome of hybrid failure in plants is caused by plant paranoia – regardless of the presence of enemies, plants “think” they are being attacked by pathogens. Over the past decade, we have studied in detail the underlying genetics, finding that often one or two loci encoding NLR immune receptors are causal. NLRs make up the most variable gene family in plants, and it is not surprising that they are often involved in genome-genome conflicts. Hybrid necrosis results when NLR genes meet that have not been co-adapted. This has in turn raised the question of the scale of NLR diversity, and our goal for the next decade is to understand the genomic and geographic patterns of immune system and especially NLR diversity. In 2018, we initiated a project, PATHO(gens in Arabi)DOPSIS, in which we aim to describe genetic diversity in the host A. thaliana and two of its important pathogens, the generalist Pseudomonas sp. and the specialist Hyaloperonospora arabidopsidis. The long-term vision is to produce maps of resistance alleles in the host, and of effector alleles in the pathogens, in order to learn when the pathogens win in a wild plant pathosystem – and when the hosts prevail. Detlef Weigel, a German-American scientist, is currently Executive Director of the Max Planck Institute for Developmental Biology. He is a member of the US National Academy of Sciences, the German National Academy of Sciences Leopoldina and the Royal Society, and recipient of several scientific awards. The first major finding from his lab was that an Arabidopsis gene could dramatically accelerate flowering of trees; this established a proof of concept for Arabidopsis genetics as a platform for biotechnological discoveries. His group later discovered the first plant microRNA mutant and identified the factor that we now know to be the long sought-after mobile flower-inducing signal. Detlef was also one of the first to exploit natural genetic variation for understanding how the environment affects plant development. In recent years, this work has come to incorporate questions at the interface of evolution and ecology: How can wild plants adapt to climate change, and how do they manage to keep their pathogens at bay? In addition to hypothesis-driven research, his group has a long history of providing new technologies and resources to the community. This has culminated in a collaborative effort to sequence the genomes of over 1,000 natural A. thaliana strains (The 1001 Genomes Project). Detlef has an extensive record of service to the scientific community, having served on a series of editorial and advisory boards. He is a forceful advocate of open access publishing and founding Deputy Editor of eLife. He is a co-founder of three biotech startups.
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    Next Gen Immunology 2020

    Date:
    02
    Sunday
    February
    2020
    -
    05
    Wednesday
    February
    2020
    Conference
    Time: 08:00
    Location: Michael Sela Adutitorium
    Organizer: The M.D. Moross Institute for Cancer Research,Azrieli Institute for Systems Biology,The Nancy and Stephen Grand Center for Sensors and Security

    Chemical and Biological Physics Dept Seminar

    Date:
    28
    Tuesday
    January
    2020
    Lecture / Seminar
    Time: 11:00
    Title: Wide-Field Single Photon-Counting Imaging for Fast and Highly Sensitive In Vivo Cell Tracking
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr Rinat Ankri
    Organizer: Department of Chemical and Biological Physics
    Abstract: Biomolecular imaging at the preclinical stage is an essential tool in various bi ... Read more Biomolecular imaging at the preclinical stage is an essential tool in various biomedical research areas such as immunology, oncology or neurology. Among all modalities available to date, optical imaging techniques play a central role, while fluorescence, in particular in the NIR region of the spectrum, provides high sensitivity and high specificity with relatively cheap instrumentation. Several whole-body optical pre-clinical NIR imaging systems are commercially available. Instruments using continuous wave (CW or time-independent) illumination allow basic small animal imaging at low cost. However, CW techniques cannot provide fluorescence lifetime contrast, which allows to probe the microenvironment and affords an increased multiplexing power. In the first part of my talk I will introduce our single photon, time-gated, phasor-based fluorescence lifetime Imaging method which circumvents limitations of conventional techniques in speed, specificity and ease of use, using fluorescent lifetime as the main contrast mechanism. In the second part of my talk I will present the tracking and multiplexing of two different cell populations, based on their different lifetimes (following their fluorescent dyes-loading). Despite major advantages of optical based NIR imaging, the reason that NIR imagers are not clinically used, is that only very few such fluorescent molecules absorb and emit in the NIR (or in the shortwave infrared, SWIR region), and even fewer have favorable biological properties (and FDA approval). I will introduce small lung cancer and dendritic cells tracking using small polyethylene glycol/phosphatidylethanolamine (PEG–PE) micelles loaded with NIR dyes (using commercial dyes as well as dyes synthesized in Prof. Sletten’s lab, UCLA Chemistry Dept.). Micelles’ endocytosis into cells affords efficient loading and exhibits strong bio stability, enabling to track the loaded cells for several days using these formulations, even though dyes were diluted by cells division (leading to reduced dye concentration within the dividing cells). Moreover, fluorescent lifetime contrast (achieved through our time-gated imaging method), significantly improved these cells detection. These advances in NIR fluorescence based imaging open up new avenues toward NIR and SWIR imaging for biomedical applications, such as tracking and monitoring cells during immunotherapy and/or drug delivery (treatment monitoring) for various types of disease.
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    Regulating the regulators:

    Date:
    23
    Thursday
    January
    2020
    Lecture / Seminar
    Time: 14:00
    Title: Regulation of NK cell intracellular inhibitory immune checkpoint to govern anti-tumor immunity
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Mira Barda-Saad
    Organizer: Department of Biological Regulation

    Guest seminar- Dr. Livnat Jerby-Arnon, will lecture on "Dissecting immune evasion mechanisms in cancer using single-cell technologies”

    Date:
    19
    Sunday
    January
    2020
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Wolfson Building for Biological Research
    Organizer: Department of Immunology

    Malaria Parasites Secrete Proteasome-Containing Vesicles to Alter its Red Blood Cell Host

    Date:
    07
    Tuesday
    January
    2020
    Lecture / Seminar
    Time: 10:00-10:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Elya Dekel
    Organizer: Department of Biomolecular Sciences
    Details: Elya Dekel - Dept. of Biomolecular Sciences-WIS
    Abstract: Malaria, caused by Plasmodium falciparum (Pf), is a devastating parasitic diseas ... Read more Malaria, caused by Plasmodium falciparum (Pf), is a devastating parasitic disease affecting hundreds of millions of people worldwide. Many pathogens use Extracellular Vesicles (EVs), to manipulate their hosts by diverting host signaling pathways to facilitate infection. In this study, we investigated the role of EVs secreted from Pf-infected red blood cells (RBCs) in altering their residing host. Using AFM-based assay, we found that the parasitic EVs significantly modify the host membrane and make it softer. Importantly, we demonstrate that the cytoskeletal structure of the RBC is being disrupted upon treatment with these EVs. Remarkably, by proteomic analysis we identified the 20S proteasome in Pf-derived EVs and further verified this complex is active within the parasitic-EVs. We further demonstrated the involvement of the 20S proteasome in host cytoskeleton degradation. This cytoskeleton degradation by the 20S proteasome leads to “priming” of naive RBC (uRBC) and thus to elevated parasitemia levels. Our results demonstrate, for the first time, that Pf-derived EVs alter both mechanical and molecular properties of their immediate host, the RBCs, by delivering active 20S proteasome and for the benefit of the parasite.
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    Adaptation of bacteria with CRISPR and adaptation on a rugged fitness landscape

    Date:
    06
    Monday
    January
    2020
    Lecture / Seminar
    Time: 14:15
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Marija Vucelja
    Organizer: Department of Physics of Complex Systems
    Abstract: I will tell you two stories of adaptation of populations aided and enriched by s ... Read more I will tell you two stories of adaptation of populations aided and enriched by statistical physics approaches. The first story is about the adaptation of bacteria with CRISPR. CRISPR-Cas is a famous biology buzz word, due to its applications to gene editing. However, CRISPR-Cas is also a prokaryote immune system. It works as a “library” of previous infections. This library contains snippets of exogenous genetic material. With a new infection, the library is consulted, and if a match is found, the attempt will be made to neutralize the intruding genome. Bacteria use CRISPR-Cas as an immune system against phages and plasmids. Such immunity is hereditary and dynamic — it can be gained and lost during the lifetime of the single bacteria. Also, the process of acquiring snippets when exposed to the same phage is stochastic, and the same strain bacteria in a population contain different CRISPR loci content and thus variable immunity to the phage. We use dynamical systems approaches to predict the shape of this diverse distribution of CRISPR loci content within a bacterial population as a function of two crucial parameters — the rate of acquisition and the immunity to the phage. The second story is about adaptation on a rugged fitness landscape. A crude measure of adaption to a new environment called fitness. Often one defines fitness as the expected growth rate. The higher the fitness, the more thriving is a population. What happens over long times for a population with a finite genome — when all beneficial, fitness mutations, are exhausted? Contrary to expectations, the experiments show that fitness does not reach a plateau. Here we introduce a spin-glass microscopic model, where a genome can be represented as a spin configuration, and individual spins are genes. The fitness plays the role of minus the Hamiltonian of the system. We use numerical approaches and estimates to study hopping between metastable states on a rugged fitness landscape. We show that with gene interactions (interacting spins), double beneficial mutations (flipping of pairs of spins) can lead to a slow, logarithmic increase of fitness in a wide class of cases.
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    Adaptation of bacteria with CRISPR and adaptation on a rugged fitness landscape

    Date:
    06
    Monday
    January
    2020
    Lecture / Seminar
    Time: 14:15
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Marija Vucelja
    Organizer: Department of Physics of Complex Systems
    Abstract: I will tell you two stories of adaptation of populations aided and enriched by s ... Read more I will tell you two stories of adaptation of populations aided and enriched by statistical physics approaches. The first story is about the adaptation of bacteria with CRISPR. CRISPR-Cas is a famous biology buzz word, due to its applications to gene editing. However, CRISPR-Cas is also a prokaryote immune system. It works as a “library” of previous infections. This library contains snippets of exogenous genetic material. With a new infection, the library is consulted, and if a match is found, the attempt will be made to neutralize the intruding genome. Bacteria use CRISPR-Cas as an immune system against phages and plasmids. Such immunity is hereditary and dynamic — it can be gained and lost during the lifetime of the single bacteria. Also, the process of acquiring snippets when exposed to the same phage is stochastic, and the same strain bacteria in a population contain different CRISPR loci content and thus variable immunity to the phage. We use dynamical systems approaches to predict the shape of this diverse distribution of CRISPR loci content within a bacterial population as a function of two crucial parameters — the rate of acquisition and the immunity to the phage. The second story is about adaptation on a rugged fitness landscape. A crude measure of adaption to a new environment called fitness. Often one defines fitness as the expected growth rate. The higher the fitness, the more thriving is a population. What happens over long times for a population with a finite genome — when all beneficial, fitness mutations, are exhausted? Contrary to expectations, the experiments show that fitness does not reach a plateau. Here we introduce a spin-glass microscopic model, where a genome can be represented as a spin configuration, and individual spins are genes. The fitness plays the role of minus the Hamiltonian of the system. We use numerical approaches and estimates to study hopping between metastable states on a rugged fitness landscape. We show that with gene interactions (interacting spins), double beneficial mutations (flipping of pairs of spins) can lead to a slow, logarithmic increase of fitness in a wide class of cases.
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    Host Pathogen Club

    Date:
    01
    Wednesday
    January
    2020
    Lecture / Seminar
    Time: 14:00-16:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Gili Rosenberg and Neta Schlezinger
    Organizer: Department of Biological Regulation

    Sela Symposium

    Date:
    19
    Thursday
    December
    2019
    Conference
    Time: 08:00
    Location: David Lopatie Conference Centre
    Organizer: Department of Immunology

    At the Interface between Organic and Inorganic Matter: Interactions and Design of Simple Functional Coatings

    Date:
    18
    Wednesday
    December
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Meital Reches
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Several natural processes are mediated by the interactions between organic and ... Read more Several natural processes are mediated by the interactions between organic and inorganic materials. The immune response towards an implant inserted into the body is mediated by proteins. Composite materials are formed by the interactions of organic materials (usually proteins) and minerals. Biofouling, the process in which organisms attached to surfaces, is also mediated by organic molecules. Understanding the nature of interactions between organic and inorganic materials will bring to the development of improved implants, new composites and antifouling materials. This lecture will present single-molecule force spectroscopy measurements of the interactions between individual biomolecules (either amino acid residues or short peptides) and inorganic surfaces in aqueous solution. Using this method, we were able to measure low adhesion forces and could clearly determine the strength of interactions between individual amino acid residues and inorganic substrates. Our results with peptides also shed light on the factors that control the interactions at the organic-inorganic interface. Based on our knowledge from single molecule experiments, we designed a short peptide (tripeptide) that can spontaneously form a coating that resists biofilm formation. Our results clearly demonstrate the formation of a coating on various surfaces (glass, titanium, silicon oxide, metals and polymers). This coating prevents the first step of antifouling, which involves the adsorption of bioorganic molecules to the substrate. In addition, it significantly reduces the attachment of various organisms such as bacteria and fungi to surfaces. Another variation of this peptide can encourage the adhesion of mammalian cells while preventing biofilm formation.
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    In vivo multimodality imaging of immune-vascular interactions in cardiovascular disease

    Date:
    12
    Thursday
    December
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Katrien Vandoorne
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Cardiovascular disease is a result of genetic and environmental risk factors tha ... Read more Cardiovascular disease is a result of genetic and environmental risk factors that together generate arterial and cardiac pathologies. Blood vessels connect multiple organ systems throughout the entire body allowing organs to interact via circulating messengers. Multimodality imaging achieves integration of these interfacing systems’ distinct processes, quantifying interactions that contribute to cardiovascular disease. Noninvasive multimodality imaging techniques are emerging tools that can further our understanding of this complex and dynamic interplay. Multichannel multimodality imaging including optics, CT, PET and MRI, are particularly promising because they can simultaneously sample multiple biomarkers. As the opportunities provided by imaging expand, mapping interconnected systems will help us decipher the complexity of cardiovascular disease and monitor novel therapeutic strategies.
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    Engage and Evade, or Perish – A Viral Quest for a Host Cell while Eluding Immune Responses

    Date:
    25
    Monday
    November
    2019
    Colloquium
    Time: 11:00-12:15
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Ron Diskin
    Organizer: Faculty of Chemistry

    Chemical Physiology of Antibody Conjugates and Natural Products

    Date:
    19
    Tuesday
    November
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Dr. Goncalo Bernardes
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Our research uses chemistry principles to address questions of importance in lif ... Read more Our research uses chemistry principles to address questions of importance in life sciences and molecular medicine. This lecture will cover recent examples of emerging areas in our group in: (i) methods developed for site-selective chemical modification of proteins at cysteine, disulfide and lysine and their use to build stable and functional protein conjugates for in vivo applications [1–4] (ii) bioorthogonal cleavage reactions for targeted drug activation in cells [5,6] (iii) by identifying on- and off-targets for anti-cancer entities using our own machine intelligence platform, unveiling the underlying molecular mechanisms of target recognition and linking drug target binding to modulation of disease, we explore the use of natural products as selective cancer modulators [7] Recent Publications: 1. Bernardim B; Cal PMSD; Matos MJ; Oliveira BL; Martínez-Sáez N; Albuquerque IS; Corzana F; Burtoloso ACB; Jiménez-Osés G; Bernardes GJL* Stoichiometric and Irreversible Cysteine-selective Protein Modification using Carbonylacrylic Reagents. Nat. Commun. 2016, 7, 13128. 2. Martínez-Saez N; Sun S; Oldrini D; Sormanni P; Boutureira O; Carboni F; Compañón I; Deery MJ; Vendruscolo M; Corzana F; Adamo R; Bernardes GJL* Oxetane Grafts Installed Site-Selectively on Native Disulfides to Enhance Protein Stability and Activity In Vivo. Angew. Chem. Int. Ed. 2017, 47, 14963–14967. 3. Freedy AM; Matos MJ; Omar Boutureira O; Corzana F; Guerreiro A; Somovilla VJ; Rodrigues T; Nicholls K; Xie B; Jiménez-Osés G; Brindle KM; Neves AA; Bernardes GJL* Chemoselective Installation of Amine Bonds on Proteins Through Aza-Michael Ligation. J. Am. Chem. Soc. 2017, 139, 18365–18375. 4. Matos MJ; Oliveira BL; Martínez-Sáez N; Guerreiro A; Cal PMSD; Bertoldo J; Maneiro M; Perkins E; Howard J; Deery MJ; Chalker JM; Corzana F; Jiménez-Osés G; Bernardes GJL* Chemo and regioselective lysine modification on native proteins. J. Am. Chem. Soc. 2018, 140, 4004–4017. 5. Stenton BJ; Oliveira BL; Matos MJ; Sinatra L; Bernardes GJL* A Thioether-directed Palladium-cleavable Linker for Targeted Bioorthogonal Drug Decaging. Chem. Sci. 2018, 9, 4185–4189. 6. Sun S; Oliveira BL; Jiménez-Osés G; Bernardes GJL* Radical-mediated thiol-ene strategy for photoactivation of thiol-containing drugs in cancer cells. Angew. Chem. Int. Ed. 2018, DOI: 10.1002/anie.201811338. 7. Rodrigues T; Werner M; Roth J; da Cruz EHG; Marques MC; Akkapeddi P; Lobo SA; Koeberle A; Corzana F; da Silva Júnior EN; Werz O; Bernardes GJL* Machine intelligence decrypts β-lapachone as an allosteric 5-lipoxygenase inhibitor. Chem. Sci. 2018, 9, 6885–7018.
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    The prospect of immunotherapy to combat Alzheimer's disease and dementia: the key role of the brain's choroid plexus

    Date:
    12
    Tuesday
    November
    2019
    Lecture / Seminar
    Time: 12:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Michal Schwartz
    Organizer: Department of Brain Sciences
    Details: Host: Dr. Meital Oren meital.oren@weizmann.ac.il tel: 6479 For assistance w ... Read more Host: Dr. Meital Oren meital.oren@weizmann.ac.il tel: 6479 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
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    Abstract: The brain is no longer considered a completely autonomous tissue with respect t ... Read more The brain is no longer considered a completely autonomous tissue with respect to its immune activity. Rather, immune surveillance is required for supporting brain functional plasticity and repair. Essential immune cells include the microglia, the resident immune cells of the brain, and circulating immune cells. Both the resident microglia and the circulating immune cells are under tight regulatory control to allow risk-free benefit from immunological interventions. We found that access of circulating immune cells to the brain is controlled by the brain’s epithelial barrier, the blood cerebrospinal barrier. Using immunological and immunogenomic tools, we discovered that in brain aging and under neurodegenerative conditions, this barrier does not optimally function to enable brain repair. We further showed in mouse models of Alzheimer’s disease (AD), that activating the immune system by immunotherapy directed against the inhibitory PD-1/PD-L1 immune checkpoint pathway drives an immune-dependent cascade of processes that start in the periphery and culminate with recruitment of monocyte-derived macrophages to the brain, which contribute to disease modification, reversing and slowing-down cognitive loss, reducing brain inflammation, and mitigating disease pathology in a mouse models of AD and Dementia (tauopathy). Overall, our results indicate that targeting the immune system outside the brain, rather than brain-specific disease-escalating factors within the central nervous system, can potentially provide a multi-dimensional disease-modifying therapy for AD and dementia.
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    The Departments of Immunology and Molecular Genetics- Special Guest Seminar:Dr. Eric Shifrut ,will lecture about "Engineering human T cell therapies using CRISPR discovery platforms”

    Date:
    02
    Tuesday
    July
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Wolfson Building for Biological Research
    Lecturer: Dr. Eric Shifrut
    Organizer: Department of Immunology

    Automated optimisation of antibody variable fragments directly from sequence.

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

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

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

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

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

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

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

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

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

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

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

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

    Date:
    31
    Sunday
    March
    2019
    Lecture / Seminar
    Time: 15:30-16:30
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Istvan Furo
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: The seminar summarizes three recent studies (1,2,3) since that share some comm ... Read more The seminar summarizes three recent studies (1,2,3) since that share some common elements: they concern porous materials and the method used is NMR spectroscopy. Yet, the aims differ. In the first study (1), the unknown is the pore structure. In particular, pore structure in hydrogels is difficult to access as water cannot be removed without affecting the pores and in the presence of water the well-honed gas sorption and mercury porosimetries just do not work. The method we invented to remedy this situation is called size-exclusion quantification (SEQ) NMR and it can be seen as the multiplexed analogue of inverse size exclusion chromatography. In effect, we sample by diffusion NMR the size distribution in a polydisperse polymer solution before and after it had been equilibrated with a porous matrix. Size-dependent polymer ingress reveals the pore structure. The method has several advantages over possible alternatives, not least its speed. In the second study (2), we sample the self-diffusion of neat water and other molecules like dimethyl sulfoxide (DMSO) and their mixtures by NMR diffusion experiments for those fluids imbibed into controlled pore glasses (CPG, pore size range 7.5 to 73 nm). Their highly interconnected structure is scaled by pore size and exhibits pore topology independent of size. Relative to the respective diffusion coefficients obtained in bulk phases, we observe a reduction in the diffusion coefficient that is independent of pore size for the larger pores and becomes stronger toward the smaller pores. Geometric tortuosity governs the behavior at larger pore sizes, while the interaction with pore walls becomes the dominant factor toward smaller pore diameters. Deviation from the trends predicted by the popular Renkin equation and variants (4) indicates that the interaction with the pore wall is not just a simple steric one. In the third study (3), the porous material is hydrated cellulose. In that matrix, we identify by using 2H MAS NMR two different groups of water molecules being in slow exchange with each other. Water molecules in one of the groups exhibit anisotropic molecular motions with a high order parameter. Based on, among other things, the observed behavior with increasing vapor pressure, we argue that this water is an integral structural element of the cellulose fibril, that itself is an aggregate of the basic units, the cellulose nanofibrils.
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    glucose-dependent insulinotrophic polypeptide (GIP )regulates whole body energy homeostasis via its effects on immune cells

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

    The clever way Vibrio invades, forming a protective, intracellular niche in host cells.

    Date:
    18
    Monday
    March
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Title: Host-pathogen interactions club
    Location: Max and Lillian Candiotty Building
    Lecturer: Prof. Kim Orth
    Organizer: Department of Biological Regulation

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

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

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

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

    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 ... Read more 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.
    Close abstract

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

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

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

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

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

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