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Molecular basis of misfolding diseases - human lysozyme as an amyloidogenic protein model

Objective



Research objectives and content
Amyloidosis is associated with a range of major diseases such as Alzheimer's and Creutzfeld-Jabob's. Amyloid fibril formation is due to the accumulation of a normally soluble protein in a non soluble conformation. Different results suggest that this abnormal aggregation is due to misfolding of the protein which forms the aggregates. For this reason the study of the folding pathways involded in systemic amyloidosis due to lysozyme mutants seems to be a major way to understand the amyloidosis process common to every amyloidic disease. Lysozyme folding has been extensively studied, and the comparison of wild type protein and mutant proteins forming the aggregates should allow to identify the intermediate responsible for aggregation, and probably to design an inhibitor to stop this aggregation. Denis Canet will be involved in this project for its kinetic expertise, to study the unfolding and refolding kinetics of the human lysozyme mutants, and to characterize the structure of the folding intermediate leading to aggregation. His ability to run rapid kinetic experiments, and to interprete the data collected, particularly with the help of computer simulations, will be of great interest for this project, in a work in collaboration with protein structure and amyloidosis specialists.
Training content (objective, benefit and expected impact)
Insight into the amyloidic aggregation process. Training in protein folding and structure, and new techniques such as real time NMR.

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Address
South Parks Road
OX1 3QT Oxford
United Kingdom

Participants (1)

Not available
France