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Content archived on 2024-06-20

Study of amyloid formation by means of solid and liquid State NMR

Objective

Amyloidosis is a general term for several feared diseases such as Alzheimer's disease, Parkinson's disease, the spongiform encephalopathies (Creutzfeld Jacob, mad cow diseases), type-2 diabetes etc. These diseases have the same scheme: an aggregation of a given protein, depending on the specific disease, forming insoluble amyloid fibrils. Recently, the amyloid fibrils have been showed to be heterogeneous depending on the maturation process length.

This project will focus on the determination of the degree o f packing errors of amyloid fibrils from peptides of 6 to 8 residues derived from the Alzheimer peptide using:
- Liquid-state NMR:The deuterium/hydrogen exchange will give some structural information as well as indication on the heterogeneity of the amyloid fibrils.
- Solid-state NMR:
PISEMA experiments on 15N and (15N chemical shift / 15N-1H dipolar coupling) to characterize both the homogeneous fibril structure as well as the heterogeneous structure via the so-called PISA wheel.
Fast MAS 1H of largely deuterated samples combined with HETCOR experiments with 13C and 15N to get structural information.
2H NMR to determine the quadru-polar tensor, which is very sensitive to the homogeneous/heterogeneous character of the molecules.
14N overtone NMR to determined the homogeneity / heterogeneity of the amyloid that can be extracted from the 14N quadru-polar tensor. 14N NMR has never been done on biological molecules so far because of its very broad signal that will necessitate the use of overtone NMR with a micro-coil. All the solid-state NMR experiments will use a solenoid micro-coil recently developed in the group of Prof. Kentgens.

- In addition scanning probe microscopy will be used to check the liquid-state D/H studies. The combination of all these techniques should prove to give valuable insights into the molecular nature and degree of packing errors in amyloid fibrils, which might be the key to design a cure for these protein-misfolding diseases.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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Call for proposal

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FP6-2002-MOBILITY-5
See other projects for this call

Funding Scheme

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EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

STICHTING KATHOLIEKE UNIVERSITEIT
EU contribution
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Total cost

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