A single molecule view of signaling complexes in health and disease

by Prof. Eilon Sherman

Racah Institute of Physics, The Hebrew University

at Biological and soft-matter physics

Thu, 12 May 2022, 12:10
Sacta-Rashi Building for Physics (54), room 207

Abstract

Signaling complexes are out-of-equilibrium, heterogeneous multi-molecular structures and sites for intracellular signal transduction. Although they play a crucial role in cellular activation, current research techniques have not been able to resolve their structure and formation mechanisms in intact cells. I will briefly review recent advancements in far-field super-resolution optical microscopy and present a multi-color Single Molecule Localization Microscopy (SMLM) approach. This approach enables imaging of multiple types of single molecules in fixed and live cells, with resolution down to ~20nm. I will further describe a statistical framework to determine the nanoscale organization and cooperativity of molecular interactions in signaling complexes. Using these techniques, we observed that signaling complexes that determine immune (T) cell activation showed surprising patterns of nanoscale organization. Conditional second-order statistics revealed a hierarchical network of cooperative interactions between the constituent molecules. I will further describe the role of specific signaling complexes in other systems, including in melanoma cells and in viral assembly. Our results extend our understanding of the assembly, and function of signaling complexes and are relevant to studying a wide range of multi-molecular complexes.

Created on 09-05-2022 by Feingold, Mario (mario)
Updaded on 09-05-2022 by Feingold, Mario (mario)