Understanding amyloid aggregation mechanisms of alpha- and gamma synuclein in vitro and in vivo

A key pathological hallmark of synucleopathies, including Parkinson’s Disease (PD) and Amyotrophic Lateral Sclerosis (ALS), is the formation of cytotoxic alpha-synuclein and gamma-synuclein aggregates respectively, that lead to neuronal cell death. An important mechanism how synucleopathies progress in vivo is cross-seeding and prion-like spreading from one cell-type to another. However, how syn/syn form aggregates in vivo and how they cross-seed from one neuronal cell to another is unclear. This project will combine biochemistry, structural biology and in vivo work using the C. elegans models of neurodegenerative diseases to capture how synucleopathies form during aging and how aggregate formation can be halted in the living organism. In addition to in vitro assays, we will utilize a range of bioimaging techniques (lightsheet and confocal microscopy) as well as molecule screening (affimers) to establish this. Thus, this project combines exciting areas of modern biochemistry and organismal biology that is of fundamental importance.


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http://www.astbury.leeds.ac.uk/people/staff/staffpage.php?StaffID=POH

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