Student projects - Tessa Sinnige
A wide variety of human diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases, are associated with the deposition of insoluble protein aggregates containing amyloid fibrils. The conversion of monomeric protein into amyloid fibrils has been studied extensively in test tube reactions, but how protein aggregation takes place in living cells and organisms remains poorly understood. A key difference between in vitro and in vivo conditions is the presence of factors that control correct protein folding and prevent protein aggregation, such as molecular chaperones. In our lab, we use the roundworm C. elegans as a model organism to address the mechanisms of protein aggregation in vivo. C. elegans is relatively short-lived (~2 weeks) and optically transparent, allowing us to track the aggregation of fluorescently labelled proteins in real-time.
The goal of this project is to find out how protein aggregation mechanisms are affected by the presence of chaperones and other factors in vivo, using C. elegans expressing fluorescently labelled polyglutamine (polyQ, related to Huntington’s disease) as a model system.
Over the course of this project, you will obtain insights into the biophysical mechanisms of protein aggregation, and how these relate to disease. You will be trained to work with the model organism C. elegans, and obtain experience with various fluorescence microscopy techniques.
T. Sinnige, G. Meisl, T.C.T. Michaels, M. Vendruscolo, T.P.J. Knowles, R.I. Morimoto (2020) Kinetic analysis reveals the rates and mechanisms of protein aggregation in a multicellular organism. bioRxiv 249862, https://doi.org/10.1101/2020.08.13.249862
Tessa Sinnige studies protein aggregation using C. elegans as a model organism.