A5011704747- Cellular transport and secretion
- SARS-CoV-2 and COVID-19 Research
- Lipid Membrane Structure and Behavior
- Cellular Mechanics and Interactions
- Advanced Electron Microscopy Techniques and Applications
- Extracellular vesicles in disease
- Muscle Physiology and Disorders
- interferon and immune responses
- Endoplasmic Reticulum Stress and Disease
- Genetics, Aging, and Longevity in Model Organisms
- Advanced Fluorescence Microscopy Techniques
- Photosynthetic Processes and Mechanisms
- Erythrocyte Function and Pathophysiology
- CRISPR and Genetic Engineering
- Force Microscopy Techniques and Applications
- RNA Interference and Gene Delivery
- Glycosylation and Glycoproteins Research
- Lipid metabolism and biosynthesis
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Antimicrobial Peptides and Activities
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Bacillus and Francisella bacterial research
- Advanced biosensing and bioanalysis techniques
Weizmann Institute of Science
2018-2025
Melodea (Israel)
2023
European Molecular Biology Laboratory
2015-2023
European Molecular Biology Laboratory
2015-2021
Technion – Israel Institute of Technology
2007-2014
Kennedy Center
2011
On 24th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, failed to neutralize. Titers against boosted third vaccine doses high both vaccinated individuals those Delta. Mutations knock out reduce...
During clathrin-mediated endocytosis (CME), plasma membrane regions are internalized to retrieve extracellular molecules and cell surface components. Whether occurs by direct clathrin assembly into curved lattices on the budding vesicle or initial recruitment flat membranes subsequent reshaping has been controversial. To distinguish between these models, we combined fluorescence microscopy electron tomography locate endocytic sites determine their coat shapes during invagination. The...
Correlative light and electron microscopy allows features of interest defined by fluorescence signals to be located in an micrograph the same sample. Rare dynamic events or specific objects can identified, targeted imaged tomography. To combine it with structural studies using cryo-electron tomography, must performed while maintaining specimen vitrified at liquid-nitrogen temperatures a dry environment during imaging transfer. Here we present instrumentation, software experimental workflow...
Abstract The Golgi is a dynamic organelle whose correct assembly crucial for cellular homeostasis. Perturbations in structure are associated with numerous disorders from neurodegeneration to cancer. However, whether and how dispersal of the apparatus actively regulated under stress, consequences dispersal, remain unknown. Here we demonstrate that 26S proteasomes cytosolic surface membranes facilitate Apparatus-Related Degradation (GARD) degradation GM130 response stress. dependent on p97/VCP...
Abstract Endosomes are compositionally dynamic organelles that regulate signaling, nutrient status and organelle quality by specifying whether material entering the cells will be shuttled back to cell surface or degraded lysosome. Recently, membrane contact sites (MCSs) between endoplasmic reticulum (ER) endosomes have emerged as important players in endosomal protein sorting, dynamics motility. Here, we show PDZD8, a Synaptotagmin-like Mitochondrial lipid-binding Proteins (SMP)...
Myoblast fusion is essential for muscle development and regeneration. Yet, it remains poorly understood how mononucleated myoblasts fuse with preexisting fibers. We demonstrate that ERK1/2 inhibition (ERKi) induces robust differentiation of primary mouse through a linear pathway involving RXR, ryanodine receptors, calcium-dependent activation CaMKII in nascent myotubes. results myotube growth via at fusogenic synapse. Mechanistically, interacts regulates MYMK Rac1, CaMKIIδ/γ knockout mice...
Summary On the 24 th November 2021 sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations Spike (S) than previously reported variants. Neutralization titres Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against boosted third vaccine doses high cases both vaccinated Delta. Mutations knock out...
Mature red blood cells (RBCs) lack internal organelles and canonical defense mechanisms, making them both a fascinating host cell, in general, an intriguing choice for the deadly malaria parasite Plasmodium falciparum (Pf), particular. Pf, while growing inside its natural host, human RBC, secretes multipurpose extracellular vesicles (EVs), yet their influence on this essential cell remains unknown. Here we demonstrate that Pf parasites, cultured fresh donor blood, secrete within such EVs...
Extracellular vesicles (EVs) transfer bioactive molecules between cells in a process reminiscent of enveloped viruses. EV cargo delivery is thought to occur by protein-mediated and pH-dependent membrane fusion the cellular membrane. However, there lack methods identify proteins resolve their mechanism. We developed benchmarked an vitro biophysical assay investigate fusion. The was standardized directly comparing viral with liposomes. show that EVs retroviruses fuse liposomes mimicking...
Abstract Cells modify their internal organization during continuous state transitions, supporting functions from cell division to differentiation. However, tools measure dynamic physiological states of individual transitioning cells are lacking. We combined live-cell imaging and machine learning monitor ERK1/2-inhibited primary murine skeletal muscle precursor cells, that transition rapidly robustly proliferating myoblasts post-mitotic myocytes then fuse, forming multinucleated myotubes. Our...
A Caenorhabditis elegans cell-surface fusion protein can promote viral with mammalian cells.
Abstract Malaria is the most serious mosquito‐borne parasitic disease, caused mainly by intracellular parasite Plasmodium falciparum . The invades human red blood cells and releases extracellular vesicles (EVs) to alter its host responses. It becomes clear that EVs are generally composed of sub‐populations. Seeking identify EV subpopulations, we subject malaria‐derived size‐separation analysis, using asymmetric flow field‐flow fractionation. Multi‐technique analysis reveals surprising...
Eukaryotic cells use clathrin-mediated endocytosis to take up a large range of extracellular cargo. During endocytosis, clathrin coat forms on the plasma membrane, but it remains controversial when and how is remodeled into spherical vesicle. Here, we 3D superresolution microscopy determine precise geometry at numbers endocytic sites. Through pseudo-temporal sorting, average trajectory remodeling during endocytosis. We find that coats assemble first flat membranes 50% area before they become...
Muscle regeneration is essential for vertebrate muscle homeostasis and recovery after injury. During regeneration, stem cells differentiate into myocytes, which then fuse with pre‐existing fibres. Hence, differentiation, fusion contraction must be tightly regulated during to avoid the disastrous consequences of premature myocytes actively contracting Cytosolic calcium (Ca 2+ ), coupled both induction myogenic differentiation contraction, has more recently been implicated in regulation...
Exocrine secretion commonly employs micron-scale vesicles that fuse to a limited apical surface, presenting an extreme challenge for maintaining membrane homeostasis. Using Drosophila melanogaster larval salivary glands, we show the membranes of fused undergo actomyosin-mediated folding and retention, which prevents them from incorporating into surface. In addition, diffusion proteins lipids between vesicle surface is limited. Actomyosin contraction crumpling are essential recruiting...
Interferon-induced transmembrane proteins (IFITMs) have been shown to strongly affect influenza A virus (IAV) infectivity in tissue culture. Moreover, polymorphisms IFITM3 associated with the severity of disease humans. appears act early infection, but its mechanism action and potential interactions incoming IAV structures are not yet defined. Here, we visualized endogenous human lung epithelial cell line A549 primary airway cells employing stimulated emission depletion super-resolution...
Imaging of cells and tissues has improved significantly over the last decade. Dual-beam instruments with a focused ion beam mounted on scanning electron microscope (FIB-SEM), offering high-resolution 3D imaging large volumes fields-of-view are becoming widely used in life sciences. FIB-SEM most recently been implemented fully hydrated, cryo-immobilized, biological samples. Correlative light microscopy workflows combining fluorescence (FM) exist, whereas cryo-FM cryo-FIB-SEM not yet commonly...
Drug delivery via nanovehicles is successfully employed in several clinical settings, yet bacterial infections, forming microbial communities the form of biofilms, present a strong challenge to therapeutic treatment due resistance conventional antimicrobial therapies. Liposomes can provide versatile drug-vector strategy for biofilm treatment, but are limited by need balance colloidal stability with penetration. We have discovered liposomic functionalization strategy, using membrane-embedded...
Abstract Lipids and proteins compartmentalize biological membranes into nanoscale domains which are crucial for signaling, intracellular trafficking many other cellular processes. Studying nanodomain function requires the ability to measure protein lipid localization at nanoscale. Current methods visualizing do not meet this requirement. Here, we introduce a correlative light electron microscopy workflow image lipids (Lipid-CLEM), combining near-native probes on-section labeling by click...
Membrane fusion is fundamental to biological processes such as fertilization and viral infection. However, studying mechanisms in live cells challenging due their complex composition topography. To address this, we developed a cell-free system based on giant plasma membrane vesicles (GPMVs), enabling us study the binding of SARS-CoV-1 Spike protein with human ACE2 receptor simplified yet physiologically relevant environment. We generated two distinct GPMV populations- one mimicking other...