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Contenido archivado el 2024-05-07

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

Objetivo



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.

Ámbito científico (EuroSciVoc)

CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.

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Convocatoria de propuestas

Data not available

Coordinador

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Aportación de la UE
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Dirección
South Parks Road
OX1 3QT OXFORD
Reino Unido

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Coste total
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Participantes (1)