A5078646809- Cellular transport and secretion
- Cell Image Analysis Techniques
- Advanced Fluorescence Microscopy Techniques
- Lipid Membrane Structure and Behavior
- Pancreatic function and diabetes
- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Erythrocyte Function and Pathophysiology
- Retinal Development and Disorders
- Calcium signaling and nucleotide metabolism
- Gene Regulatory Network Analysis
- Endoplasmic Reticulum Stress and Disease
- Hippo pathway signaling and YAP/TAZ
- Neuroscience and Neuropharmacology Research
- AI in cancer detection
- Pediatric Hepatobiliary Diseases and Treatments
- Medical Image Segmentation Techniques
- RNA Interference and Gene Delivery
- Advanced Electron Microscopy Techniques and Applications
- Mathematical Biology Tumor Growth
- Diabetes and associated disorders
- Photoreceptor and optogenetics research
- Diabetes Management and Research
Max Planck Institute of Molecular Cell Biology and Genetics
2016-2025
Lomonosov Moscow State University
2013-2024
Max Planck Institute for the Physics of Complex Systems
2007-2018
Moscow State University
2015-2018
Max Planck Society
2009-2014
University of Geneva
2007
The first community competition designed to objectively compare the performance of particle tracking algorithms provides valuable practical information for both users and developers. Particle is key importance quantitative analysis intracellular dynamic processes from time-lapse microscopy image data. Because manually detecting following large numbers individual particles not feasible, automated computational methods have been developed these tasks by many groups. Aiming perform an objective...
In the developing fly wing, secreted morphogens such as Decapentaplegic (Dpp) and Wingless (Wg) form gradients of concentration providing positional information. Dpp forms a longer-range gradient than Wg. To understand how range is controlled, we measured four key kinetic parameters governing morphogen spreading: production rate, effective diffusion coefficient, degradation immobile fraction. The had different values for versus addition, Dynamin-dependent endocytosis was required spreading...
Delivery of exogenous mRNA using lipid nanoparticles (LNPs) is a promising strategy for therapeutics. However, bottleneck remains in the poor understanding parameters that correlate with endosomal escape versus cytotoxicity. To address this problem, we compared distribution six LNP-mRNA formulations diverse chemical composition and efficacy, similar to those used mRNA-based vaccines, primary human adipocytes, fibroblasts, HeLa cells. Surprisingly, found total uptake not sufficient predictor...
Binding of epidermal growth factor (EGF) to its receptor leads dimerization, assembly protein complexes, and activation signaling networks that control key cellular responses. Despite their fundamental role in cell biology, little is known about complexes associated with the EGF (EGFR) before stimulation. We used a modified membrane yeast two-hybrid system together bioinformatics identify 87 candidate proteins interacting ligand-unoccupied EGFR. Among them was histone deacetylase 6 (HDAC6),...
An outstanding question is how receptor tyrosine kinases (RTKs) determine different cell-fate decisions despite sharing the same signalling cascades. Here, we uncovered an unexpected mechanism of RTK trafficking in this process. By quantitative high-resolution FRET microscopy, found that phosphorylated epidermal growth factor (p-EGFR) not randomly distributed but packaged at constant mean amounts endosomes. Cells respond to higher EGF concentrations by increasing number endosomes keeping...
A prerequisite for the systems biology analysis of tissues is an accurate digital three-dimensional reconstruction tissue structure based on images markers covering multiple scales. Here, we designed a flexible pipeline multi-scale and quantitative morphological architecture from microscopy images. Our includes newly developed algorithms that address specific challenges thick dense reconstruction. implementation allows workflow, scalable to high-throughput applicable various mammalian...
Endocytosis allows cargo to enter a series of specialized endosomal compartments, beginning with early endosomes harboring Rab5 and its effector EEA1. There are, however, additional structures labeled by the APPL1 whose role in endocytic transport remains unclear. It has been proposed that vesicles are intermediates convert into EEA1 endosomes. Here, we tested this model analyzing ultrastructural morphology, kinetics transport, stability compartment over time. We found resides on...
Bile, the central metabolic product of liver, is transported by bile canaliculi network. The impairment flow in cholestatic liver diseases has urged a demand for insights into its regulation. Here, we developed predictive 3D multi-scale model that simulates fluid dynamic properties successively from subcellular to tissue level. integrates structure canalicular network mouse lobule, as determined high-resolution confocal and serial block-face scanning electron microscopy, with measurements...
Localized translation is vital to polarized cells and requires precise robust distribution of different mRNAs ribosomes across the cell. However, underlying molecular mechanisms are poorly understood important players lacking. Here, we discovered a Rab5 effector, five-subunit endosomal RNA/ribosome intermediary (FERRY) complex, that recruits early endosomes through direct mRNA-interaction. FERRY displays preferential binding certain groups transcripts, including encoding mitochondrial...
Key cellular functions and developmental processes rely on cascades of GTPases. GTPases the Rab family provide a molecular ID code to generation, maintenance transport intracellular compartments. Here, we addressed design principles endocytosis by focusing conversion early endosomes into late endosomes, which entails replacement Rab5 Rab7. We modelled this process as cascade functional modules interacting demonstrate that intermodule interactions share similarities with toggle switch...
Early endosomes are organized in a network of vesicles shaped by cycles fusion, fission, and conversion to late endosomes. In yeast, endosome fusion regulated, among others, CORVET, hexameric protein complex. the mammalian endocytic system, distinct subpopulations early labelled Rab5 effectors APPL1 EEA1 present. Here, function CORVET with respect these endosomal was investigated. Tgfbrap1 as CORVET-specific subunit functional ortholog Vps3p identified, demonstrating that it is...
Exploring the cell biology of hepatocytes in vitro could be a powerful strategy to dissect molecular mechanisms underlying structure and function liver vivo. However, this approach relies on appropriate culture systems that can recapitulate biological metabolic features whilst being accessible experimental manipulations. Here, we adapted protocols for high-resolution fluorescence microscopy quantitative image analysis compare two primary hepatocyte systems, monolayer collagen sandwich, with...
Significance Insulin is key for control of glucose homeostasis in vertebrates. Insufficient insulin secretion relative to metabolic needs causes diabetes. Pancreatic beta cells store into secretory granules (SGs), which release extracellularly upon fusion with the plasma membrane. SGs exist different functional pools, newly generated being preferentially secreted. Here we show that aged display reduced competence glucose-stimulated microtubule-mediated transport and are disposed within...