Bridging Time and Length Scales in Pathological Protein Aggregation

BIOENGINEERING SEMINAR
 
Abstract:
Over 50 medical disorders, including Alzheimer’s disease, Parkinson’s disease and Type-II diabetes, are intimately connected with the aggregation of precursor peptides and proteins into pathological fibrillar structures known as amyloids. To design rational therapeutic strategies against these protein aggregation diseases it is thus imperative to quantify the fundamental principles that control pathological aggregation into amyloid fibrils. The fundamental challenge in establishing such an understanding in a rigorous manner is the disparate nature of the spatial and temporal scales involved. In this talk, I will demonstrate how we can address this challenge by bringing the power of quantitative methods rooted in statistical physics and applied mathematics to protein aggregation. I will first discuss a unified theory of protein aggregation kinetics and show how it provides the basis for interpreting experimental aggregation kinetics data in terms of specific microscopic mechanisms controlling the proliferation of fibrils. I will then apply the resulting methods to shed light on the fundamental molecular mechanisms of the dynamics of toxic oligomers of the Amyloid-β peptide Aβ42 of Alzheimer’s disease. I will also discuss how theory can guide us in the development of rational strategies for controlling aberrant protein aggregation in time and space. In particular, I will bring together protein aggregation kinetics with optimal control theory to determine explicit optimal administration protocols for drugs that inhibit specific molecular events during the aggregation process. I will finally introduce modern ideas from liquid-liquid phase separation to investigate how liquid cellular compartments could be implicated in spatially regulating protein aggregation.

Bio:
Employment History:
07/2016 - Present:  Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA
Swiss National Science Foundation Postdoctoral Fellow in Applied Mathematics
10/2016 - Present:  Peterhouse, University of Cambridge, United Kingdom
Junior Research Fellow in Physics.

Eduation:
10/2012 - 06/2016:  PhD in Physical Chemistry, University of Cambridge, United Kingdom
09/2010 - 06/2012:  Master of Science ETH in Mathematics, ETH Zürich, Switzerland
09/2010 - 06/2012:  Master of Science ETH in Physics, ETH Zürich, Switzerland
09/2007 - 06/2010:  Bachelor of Science ETH in Physics, ETH Zürich, Switzerland.


Zoom link for attending remotely:  https://epfl.zoom.us/j/246384287