Objective
The question of how the sequence of amino acids dictates the final fold of globular proteins remains one of the fundamental riddles of structural biology. The objective of the present research plan is to identify sequence elements that contribute key local and non-local interactions that are effective during the initial steps of the folding process.
A series of experiments are proposed to identify critical residues that form such effective interactions. Initial phases of the misfolding of globular and natively unfolded proteins will be explored in order to explain these processes and ultimately to control negative consequences of misfolding, e.g. formation of amyloid plaques. An interdisciplinary approach aimed primarily at structural characterization of the rapidly changing ensembles of partially folded protein molecules will be adopted. A number of methods will be applied, in particular time resolved FRET, -FRET detected FCS; FRET detected fast-kinetic methods, (a novel high pressure jump and micromixing based double kinetics experiments); protein engineering and computational methods.
The hypothesis is that few very effective non-local contacts can direct the backbone into a native like fold at the early phase of the folding transition. This hypothesis will be explored to identify the essential key interactions and specific clusters of residues that contribute to those interactions. The response of the ensembles of conformers to changes of pressure; temperature; solvent composition and to the insertion of structure perturbation mutations will be monitored. Computational and bioinformatics methods will be applied in an attempt to generalize the experimental results.
In order to achieve these goals the host research group will bring in
- methods for construction of a pressure -jump and micromixing devices;
- methods of molecular dynamics simulations, and
- the technology enabling single molecule detection.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins protein folding
- natural sciences biological sciences genetics mutation
- natural sciences physical sciences classical mechanics fluid mechanics fluid statics
- natural sciences chemical sciences organic chemistry amines
- natural sciences physical sciences optics laser physics
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2004-MOBILITY-3
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
RAMAT GAN
Israel
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.