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Content archived on 2024-06-18

Structural study of a potassium channel, KirBac3.1, using electron microscopy

Objective

Ion channels, proteins that allow the passage of ions across the membrane, have crucial roles in many important physiological processes, such as nerve and muscle excitation, cell proliferation, hormone secretion and blood pressure regulation. Thus, defects in their function cause serious diseases. Moreover, their position on the cell surface, their heterogeneity and the localized expression in particular tissues make ion channels an attractive target for many drug therapies. The study of structures and functions of ion channels may elucidate their working mechanisms and allow an efficient drug design. Potassium channels are a family of ion channels involved in the diffusion of K+ ions through the cell membrane and widely distributed in most cell types. The inwardly rectifying potassium (Kir) channels comprise a superfamily of K+ channels that regulate membrane potential and K+ transport in many cell types. In order to completely elucidate how K channels open and close it is essential to obtain a structure for the same channel in both the open and closed states. The aim of the present project is to harness cryo electron crystallography to determine the structure of KirBac3.1 channel, at sufficient resolution to identify transmembrane helices and secondary structure motifs, with a view to understand how Kir channels open and close. In the case of KirBac3.1 open state, it is possible to produce relatively large 2D crystals that can be used to calculate the 3D structure from high tilted angle images. But the growth of these large crystals is not yet reproducible. So, for the present project, the applicant, Dr. R. De Zorzi, will join the research group of Dr. C. Vénien-Bryan of the Oxford University and will test various 2D crystallization conditions in order to produce reliably lager 2D crystals. Afterwards, the researcher will take pictures of the 2D crystals with the microscopes of the Oxford and Basel laboratories, in collaboration with Prof. H. Stahlberg (Basel).

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2009-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
€ 172 740,80
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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