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Weizmann Institute of Science

Weizmann Institute of Science

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524 Projects, page 1 of 105
  • Funder: European Commission Project Code: 249148
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  • Funder: European Commission Project Code: 949364
    Overall Budget: 1,499,880 EURFunder Contribution: 1,499,880 EUR

    Synapses are intercellular junctions specialized for coordinated cell-cell communication throughout the nervous system. They are organized by cell-adhesion molecules (CAMs) that bi-directionally orchestrate neuronal communication. Latrophilins (LPHNs) are a unique sub-family of CAMs that play critical roles in structuring the synaptic architecture through multifaceted interactions with a large variety of synaptic partners. Mutations in LPHN have been associated with neurodevelopmental and neuropsychiatric disorders. Despite their gravity, the mechanism governing LPHN synaptic activities remain elusive. To further our understanding of LPHN-mediated cell-cell communication, we suggest to characterize these receptors’ interactions with their intracellular and extracellular partners. For this purpose, we propose to adopt a hybrid approach driven primarily by cryo-EM, a state-of-the-art technique capable of dissecting the molecular mechanisms of super-molecular assemblies at extremely high spatial resolutions, which is our group’s main field of expertise. The cryo-EM studies will be complemented by cryo electron tomography (cryo-ET), fluorescence microscopy and biochemical approaches. Our specific aims are: Aim 1: Dissect the molecular mechanisms of LPHN activation by combining cryo-EM with biochemical methodologies. Aim 2: Characterize the LPHN interactome through cryo-EM and fluorescence microscopy. Aim 3: Resolve the architecture of the LPHN interactome at a close-to-native environment through cryo-ET. Our experimental strategy will generate a quantitative, near-atomic resolution view of LPHNs and the mechanism by which they interact with their synaptic partners and instigate trans-synaptic signal transduction. These data will be vital for understanding LPHN-mediated cell-cell communication as well as the mechanisms governing trans-synaptic interactions and could potentially highlight novel approaches to treat neurodevelopmental and neuropsychiatric disorders.

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  • Funder: European Commission Project Code: 633888
    Overall Budget: 150,000 EURFunder Contribution: 150,000 EUR

    This proposal aims at commercializing a new method that can improve the detection and diagnosis of breast cancer. Using ultrafast magnetic resonance (MR) acquisition schemes that span off our UltraNMR ERC AdG award, we have found ways to exploit our Spatiotemporally-Encoded (SPEN) principles together with diffusion measurements, for the rapid, safe and non-invasive diagnosis of breast malignancies. This SPENmr PoC could provide much cleaner, artifact-free alternatives than existing standards; porting these methods into clinical use could reduce unnecessary biopsies, eliminate side-effects associated from contrast agent injections, expand the base of subjects that can be diagnosed without surgery, and improve the specificity of methods based on either mammography, ultrasound or contemporary MRI. All these benefits would simply require operating acquisition and processing software packages that will arise from this project, on any of the tens-of-thousands of clinical MRI scanners used nowadays worldwide for breast scanning. We consequently envision a large potential market, and a product whose successive refinements could have a lifetime of decades. Moreover, preliminary results indicate that the principles discussed in this proposal could be extended from breast to other human organs possessing an organized ductal/glandular structures –kidneys, prostate, pancreas– to analyses of stroke and to functional MRI.

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  • Funder: European Commission Project Code: 268585
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  • Funder: European Commission Project Code: 101117863
    Overall Budget: 1,499,080 EURFunder Contribution: 1,499,080 EUR

    Bacteria are social organisms that interact and coordinate their behaviors to shape our world. Whereas their clonal populations are genetically identical, they contain phenotypically distinct members. This diversity provides resilience to unpredictable environmental changes, such as antibiotic exposure or nutrient depletion. It also facilitates cooperative interactions between different sub-population via specialization in costly activities such as virulence factor production, forming an extended basis for sociality. Yet, the phenotypic landscape in any given species remains largely unexplored due to the technical challenges of profiling individual bacteria, particularly in spatially structured biofilms and host tissues. Recent breakthroughs in microbial single-cell transcriptomics, developed by the PI of the current proposal (Dar et al., Science 2021), now provide a unique opportunity to illuminate this hidden complexity. This proposal seeks a systematic and experimentally derived view of phenotypic variation. We will comparatively study pathogenic and non-pathogenic Pseudomonas species in three settings, each illuminating distinct core principles of cell-cell variability. In Objective 1, we will focus on free-living populations, building on the massive multiplexing capacity of our method to comprehensively map phenotypic cell states, outline their interplay with physiological and environmental factors, and study their evolution. We will characterize the spatiotemporal dynamics of cell states directly within 3D biofilms in Objective 2, and contextualize our results in vivo during infection in Objective 3, simultaneously measuring host-and-microbe spatial expression. Comprehensively studying phenotypic heterogeneity is a critical next step for understanding how microbes survive in complex environments, socially interact, and subvert their hosts during infection. If successfully executed, this proposal will shed light on the plasticity that defines microbial li

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