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Understanding Amyloid Post-Translational Modification at the Nanoscale

   Institute of Chemical Biology

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  Dr F Aprile, Prof R Vilar, Dr L Ying  Applications accepted all year round  Funded PhD Project (Students Worldwide)

About the Project

Alzheimer’s disease is a fatal and incurable form of dementia, affecting 40 million people worldwide. Despite the high prevalence of Alzheimer’s disease, currently, there is no cure or biometric diagnostic test for it. Small aggregates of the amyloid-beta peptide, called oligomers, cause toxicity in Alzheimer’s disease, and are associated with the disease’s onset and progression. Increasing evidence suggest that post-translational modifications alter the propensity of amyloid-beta to aggregate. However, there is currently no information on the implications of such modifications for oligomers’ structure and mechanisms, as oligomers are too heterogeneous and sparse to be studied with standard methods. To overcome this challenge, we will deliver a novel analytical platform to study oligomers at the single-molecule level. We will combine ultra-sensitive antibody detection with super-resolution microscopy and rational drug design to determine how pathological post-translational modifications affect the structure, toxicity, and druggability of amyloid-beta oligomers. Our results will provide unprecedented information on key mechanisms of Alzheimer’s disease and open new clinical intervention.

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