Abstract
Filamentous protein aggregation underlies a number of functional and pathological processes in nature. This talk focuses on the formation of amyloid fibrils, a class of beta-sheet rich protein filament. Such structures were initially discovered in the context of disease states where their uncontrolled formation impedes normal cellular function, but are now known to also possess numerous beneficial roles in organisms ranging from bacteria to humans. The formation of these structures commonly occurs through supra-molecular polymerisation following an initial primary nucleation step. In recent years it has become apparent that in addition to primary nucleation, secondary nucleation events which are catalysed the the presence of existing aggregates can play a significant role in the dynamics of such systems. This talk describes our efforts to understand the nature of the nucleation processes in protein aggregation as well as the dynamics of such systems and how these features connect to the biological roles that these structures can have in both health and disease. A particular focus will be on the development of new microfluidic approaches to study heterogeneous protein self-assembly and their application to explore the molecular determinants of amyloid formation from peptides and proteins.
Biography
Tuomas Knowles studied Biology at the University of Geneva, and Physics at ETH Zurich. He moved to Cambridge in 2004 to work towards his PhD in the Cavendish Laboratory and the Nanoscience Centre. In 2008 he was elected to a Research Fellowship at St John’s College, Cambridge, and was then appointed to a University Lectureship in Physical Chemistry in 2010, joining the faculty at the Department of Chemistry in Cambridge. He then successively held a University Readership between 2013 and 2015 and a Professorship since 2015 in the Department of Chemistry. Since 2016 he is Professor of Physical Chemistry and Biophysics in the Department of Chemistry and at the Cavendish Laboratory, and is co-director of the Cambridge Centre for Protein Misfolding Diseases in Cambridge.