USC Monthly Biophysics Seminar Series: Aggregation of Proteins

University of Southern California Monthly Biophysics Seminar Series

“Aggregation of Proteins: Growth of Glucagon Fibrils and Bacterial Growth”

Andrej Kosmrlj, Ph.D.

Assistant Professor of Mechanical and Aerospace Engineering Princeton University

Date: Friday, January 27, 2017

Time: 2:00 PM

Location: Ahmanson Center for Biology (ACB 238)

Simulcast on HSC: Herklotz Seminar Room (ZNI)

Abstract:

Misfolding and aggregation of peptides and proteins are the hallmarks of many human diseases.

With the advancement of microscopes, it is now possible to observe the kinetics of individual aggregates and fibrils in vitro. Interestingly, in some cases the growth of fibrils is intermittent, where the periods of growth are interrupted by periods of stasis. In this talk I will focus on the intermittent fibrillation of glucagon and I will describe how E. coli bacteria deal with harmful aggregates of misfolded proteins. Glucagon is a peptide hormone that upregulates blood sugar levels and is used to treat diabetic patients in situations of acute hypoglycemia. When dissolved in a fluid state, glucagon can form fibrils and become useless, as the fibrils cannot be absorbed and used by the body. The observed intermittent growth of glucagon fibrils can be explained with a simple model, where fibrils come in two forms, one built entirely from glucagon monomers and one entirely from glucagon trimers. The opposite building blocks act as fibril growth blockers, and this generic model reproduces experimental behavior well. Finally, I will discuss how E. coli bacteria deal with harmful aggregates of misfolded proteins that develop, when bacteria are under heat or antibiotic stress. In order to maximize the fitness of the whole population, bacteria distribute aggregates asymmetrically between their daughters, such that one daughter inherits the whole aggregate, while the other daughter receives none of it. Over time such asymmetric distribution of aggregates produces many “rejuvenated” bacteria with small aggregates that are quickly dividing at the expense of a few bacteria with large aggregates that are dividing very slowly.=