Seminar by Thomas Michaels

Spatiotemporal control of protein aggregation

Thomas Michaels (Cambridge University)

Over 30 medical disorders, including Alzheimer’s disease and 
Parkinson’s disease, are intimately connected with the aggregation of 
precursor peptides and proteins into pathological fibrillar structures 
known as amyloid fibrils. 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 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 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.