This Dept of Chemistry seminar will host Prof Louise Serpell from the University of Sussex and Ying Ge (Imperial College London)
Louise will be available to meet with researchers on the day, please get in touch with Elena (e.de-vita17@imperial.ac.uk) if you would like to meet with her
Agenda
13:30 – 14:00 ECR speaker: Ying Ge (Imperial College London)
Targeting Post-translational Modifications in Alzheimer’s Disease
Abstract Protein aggregates called amyloids underly many neurodegenerative diseases (NDs). Proteomics revealed that post-translational modifications (PTMs), such as acetylation, are enriched in the brains of ND patients. Accordingly, certain PTMs alter aggregation kinetics and increase cytotoxicity. Probing PTMs will facilitate the development of diagnostics and therapeutics against NDs. Our work presents methods to generate and probe PTMs in vitro.
Amyloid-β (Aβ), associated with Alzheimer’s diseases, is particularly hard to modify, due to its high hydrophobicity and tendency to precipitate. Using a solubility-enhancing fusion construct, we successfully applied chemical mutagenesis to Aβ and introduced diverse mimetics of PTMs, using molecular biology and commercially available reagents. Kinetic and structural analyses demonstrated the effects of these PTM mimetics to be comparable to authentic PTMs. To target PTM-containing Aβ, we used display technologies of synthetic camelid-derived antibodies and identified hits that show strong specificity for PTM-Aβ. We also test the effect of antibodies on aggregation and select those targeting specific conformations of Aβ.
14:00 – 15:00 Main speaker: Louise Serpell (University of Sussex)
Untangling the misfolding proteins in Alzheimer’s disease
Abstract Protein misfolding is central to many diseases including Alzheimer’s disease. However, the mechanism by which conformational change is initiated remains elusive. Alzheimer’s disease is characterised by key proteins including Tau and Amyloid-beta. However, the role of each of these in the neurodegenerative disease cascade is unclear. Our work aims to explore the initiation events that lead to misfolding and the downstream effects on neuronal function, whilst clarifying the potentially toxic species. In this talk, I will describe work that aims to uncover fundamental mechanisms at the heart of the structural changes in Amyloid-beta and tau.
15:00 – 15:30 Coffee & networking