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Quantitative approaches to unravel the molecular mechanisms of clathrin-mediated endocytosis

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SDBW04 - Spatially distributed stochastic dynamical systems in biology

Eukaryotic cells ubiquitously use clathrin-mediated endocytosis to internalize nutrients, receptors and recycle plasma membrane. Defects in endocytosis are implicated in multiple diseases such as cancer, neuropathies, metabolic syndromes, and the endocytic machinery can be hijacked by some pathogens to infect cells. During clathrin-mediated endocytosis, the endocytic machinery shapes a ~50-nm diameter vesicle from the flat plasma membrane in less than 20 seconds. When membrane tension is high, a dynamic actin cytoskeleton is necessary for endocytosis to proceed. Despite intensive studies on most of the endocytic proteins, it remains unknown how the actin network produces the forces necessary to deform the plasma membrane during endocytosis.

In this talk, we will show how the development of new quantitative methods can be key to unravel the molecular mechanisms of complex biological processes such as endocytosis. We will focus on new methods to measure the temporal evolution of a) the number of molecules of endocytic proteins, b) their residence times in the endocytic structure, c) the nanometer-scale deformations of the endocytic structure, and d) methods to increase the quality and the temporal resolution of noisy datasets. We will also show how these data are invaluable to constrain mathematical models that we have developed to test hypotheses and make experimentally testable predictions. 

This talk is part of the Isaac Newton Institute Seminar Series series.

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