A new mathematical framework for AB peptide assembly in Alzheimer's disease

Lead Research Organisation: University of Sheffield
Department Name: Molecular Biology and Biotechnology

Abstract

Protein misfolding is responsible for some of the most prevalent aging diseases. Fibrillar "amyloid" species accumulate as extracellular plaques or intracellular tangles and act as sinks for neurotoxic soluble species. Our data show that current models of protein polymerisation are inapplicable to amyloids such as AB. This is because historical models were developed for proteins with a narrow range of folds, while amyloids have complex folding landscapes and a vast array of conformations.
Our proposal is to use techniques that will remove bias in our search for mechanisms, producing emergent behaviours from simulation rather than simply confirming or negating existing theories. This represents a step-change in our approach to amyloid formation. To date, theoreticians have not taken full advantage of structural and kinetic data. The novelty of this proposal is its "multi-scale" nature and the combination of top-down and bottom up approaches

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
2109094 Studentship BB/M011151/1 30/09/2018 29/09/2022 Lianne Gahan