Objective
G-protein coupled receptors (GPCRs) are cell surface receptors that mediate the cellular responses to an enormous diversity of endogenous signaling molecules as well as environmental signals. GPCRs are a major target for the pharmaceutical industry as is reflected by the fact that more than 50% of all medicines available today act on a GPCR and represent about a quarter of the top-selling drugs worldwide. However, effective drug design and functional characterization of these receptors is strongly limited by the absence of high-resolution structural information because of the many practical problems of working with membrane proteins. Here, we propose to replace the lipid-exposed hydrophobic residues within the transmembrane domains of GPCRs with more hydrophilic residues to engineer water-soluble variants of GPCRs capable of folding in aqueous solutions. Moreover, detailed comparison of membrane proteins and soluble proteins by protein engineering will also lead to a deeper insight into membrane protein folding and stability with important consequences for the handling of drug targets. Redesigning a GPCR by substituting the hydrophobic amino acids of the protein/lipid interface with suitable polar or charged residues to produce a molecule that is able to fold and function in aqueous solution represents an ambitious protein-engineering problem of high combinatorial complexity. It is improbable that we will reach the desired result in a single step by rational design. Instead, we have chosen a highly interdisciplinary approach that combines the strengths of computational and experimental tools, of design, selection and in vitro evolution. The strategy, we propose to use, relies on the proven expertise of the Plückthun group in the rational design of protein libraries. From these libraries, functional molecules can efficiently be selected by ribosome display methods. Selected sequences can be further optimized using the techniques of directed in vitro evolution.
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.
- medical and health sciences basic medicine medicinal chemistry
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences biological sciences biochemistry biomolecules proteins protein folding
- natural sciences chemical sciences organic chemistry amines
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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.
FP7-PEOPLE-IEF-2008
See other projects for this call
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
8006 ZURICH
Switzerland
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.