Tessa Sinnige

Institute:Department of Chemistry, Cambridge University, UK
Title:Towards a molecular understanding of protein aggregation in vivo
Abstract:["Protein aggregation into amyloid fibrils is a hallmark of a variety of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases, yet the relationship between protein misfolding and cellular toxicity remains unclear. The nematode worm Caenorhabditis elegans is a useful model organism to study the molecular mechanisms of protein misfolding diseases, with the potential to directly correlate the biophysical state of the protein of interest to a behavioural read-out that reports on toxicity. However, obtaining a reliable and quantitative measure for protein aggregation in this system remains a challenge. To address this problem, we developed a fast approach for fluorescence lifetime imaging microscopy (FLIM) and used it to monitor protein aggregation throughout the lifespan of C. elegans models for Parkinson's and Huntington's diseases, leading to novel insights into the respective aggregation mechanisms. Whereas traditional animal models are based on tissue-wide protein overexpression, I will also present the generation of a new C. elegans model for Alzheimer's disease in which amyloid-beta is expressed at physiological levels in just two sensory neurons, allowing subtle perturbations in neuronal signalling to be studied."]
Host:Stefan RĂ¼diger