Translating biophysical insights of protein aggregation into understanding of disease

The formation of protein aggregates is a hallmark of a number of neurodegenerative diseases, including ALS, Parkinsons, and Alzheimers diseases. While this process can be studied in detail for purified proteins in the test tube, it has been difficult to translate the insights from such biophysical studies into an understanding of neurodegenerative disease and he rational design of effective cures. To address this challenge, my work focusses on the development of minimal mechanistic models, that based on our understanding of the underlying molecular interactions and can describe both in vitro biophysical measurements as well as the emergence and progression of disease. In this talk, I will show how such models not only enable determination of mechanisms from in vitro measurements, but also explain patterns seen at the cellular and tissue level in disease and thereby rationalise the effect of current therapeutic strategies. By analysing data on many different proteins and across diseases, we have been able to reveal some of the key determinants of pathogenicity and highlight the most promising targets for therapeutic intervention.