Lauren Rice, PhD Exit Seminar

Proteins require a ‘native’ fold to perform their essential cellular functions. However, often due to environmental or genetic factors, they can become misfolded and form aggregates.

The accumulation of these protein aggregates is associated with several diseases including Parkinson’s disease, Alzheimer’s disease and Cataracts. However, several cellular mechanisms act to maintain the folded and functional state of the proteome, including the highly conserved molecular chaperone proteins. These include the small heat shock proteins (sHsps) which prevent the aggregation of a range of client proteins, as well as the Hsp70 system which resolves misfolded states and disaggregates highly stable aggregates. The mechanistic details of how these chaperones prevent and resolve aggregated and misfolded states are not widely understood, due to the heterogeneous and dynamic nature of both molecular chaperones and aggregation. Single-molecule techniques are a powerful tool to study chaperone function and their interaction with their client proteins. This is largely owing to the capacity of single-molecule techniques to visualise rare or dynamic features in individual proteins which are typically masked in ensemble-averaging techniques. This presentation outlines the use of fluorescence-based single-molecule techniques to observe and quantify the interactions between molecular chaperones and their clients.