University of Dundee

"Turning multi-protein self-assembly by membrane localization"

Event Date: 
Monday, September 30, 2019 - 14:00 to 15:00
Event Location: 
Welcome Trust Seminar Rooms WTB-SRF and WTB-SRB
Dr David Murray
Event Speaker: 
Dr Margaret Johnson
Department of Biophysics Johns Hopkins University
Event Type: 



Clathrin-mediated endocytosis (CME) is an essential pathway used by all eukaryotes for transport across the plasma membrane; it is one of many diverse cellular pathways that require cytosolic proteins to localize and self-assemble on the membrane. A wealth of biochemical, structural, and in vivo imaging data has provided deep insight into the dynamics of endocytosis. Yet because of the complexity of the pathway, it is still remarkably difficult to predict how the stoichiometry of components, membrane bending, or coupling to ATP-driven reactions impacts cargo uptake, and this is where computational modeling can provide important insights. We recently developed novel reaction-diffusion algorithms and software that enable detailed computer simulations of nonequilibrium self-assembly over long time-scales. We have shown through theory and simulation how localization of protein binding partners to the membrane can dramatically enhance binding through dimensionality reduction, providing a trigger for assembly. As a result, we show how tuning the localization strength of proteins to the membrane, via either protein or lipid binding partners, can drive assembly and disassembly of clathrin-coated structures. This will help us to predict how the transition from early clathrin coated structures to productive vesicles is controlled in the cell. Lastly, our generalized computational methods can directly simulate a broad range of assembly processes at the cell-scale, providing a natural companion to quantitative cell biology.



Margaret Johnson joined the Biophysics faculty at Johns Hopkins University in 2013. She received her B.S. in Applied Math from Columbia University and her PhD in BioEngineering from UC Berkeley. She completed postdoctoral training in the Laboratory of Chemical Physics at the National Institutes of Health in Bethesda, MD.  Her research focuses on understanding how the individual interactions between thousands of diverse components in the cell generate order and collective function at the right time and the right place. She develops theoretical and computational approaches to study the evolution and mechanics of dynamic systems of interacting and assembling proteins.

In 2011 she received an NIH Pathway to Independence Award (K99/R00).