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Content archived on 2024-06-18

"Development of selective antagonists and subtype selective ligands for the D-myo-inositol 1,4,5-trisphosphate receptors."

Objective

"The overall aim of this project is the development of novel ligands to probe the role of D-myo-inositol 1,4,5-trisphosphate receptors (InsP3Rs) in intracellular calcium signalling. Two key goals are the development of selective and potent non-inositol InsP3R antagonists and the development of ligands that bind selectively to one of the three subtype of InsP3Rs. Using hits from an in silico screen, we will develop and then employ thermal shift analysis, surface plasmon resonance and isothermal titration calorimetry assays to identify promising lead compounds. We will determine whether these compounds act as agonists or antagonists using a fluorescence-based sea urchin egg homogenate assay before data are obtained in further, more intact, cellular assays. In order to facilitate the use of these compounds in cells they will be rendered cell permeant using previously developed technology. X-ray crystallographic studies with these compounds, in particular the antagonists, will be undertaken in order to shed light the molecular mechanism of InsP3R activation. Subtype selective ligands will be useful in determining the particular role of each of the InsP3R subtypes in normal cellular function and cellular dysfunction, which underlies diseases such as heart arrhythmia and cardiac hypertrophy. This project has been designed to capitalise on the skills of the fellow in chemical synthesis and her knowledge of phosphate bioisosteres. Further advanced training will be provided in chemical synthesis, biophysical techniques and molecular biology in addition to cooperation with industrial collaborators Inhibox. Consequently, the fellow will significantly enhance and diversify her skills in this highly multidisciplinary project."

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.

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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.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2011-IEF
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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.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
EU contribution
€ 200 371,80
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

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