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Content archived on 2024-06-18

Protection against reactive oxygen species in neurodegeneration

Objective

Oxidative stress (OS) is implicated in the pathogenesis of some of the most devastating neurological diseases. Therefore, identification of pathways that counteract oxidative damage may lead to therapeutic strategies applicable to a wide range of disorders. I have recently identified the importance of the mitochondrial oxidation resistance 1 (Oxr1) gene for neuronal survival; loss of Oxr1 causes neurodegeneration in mice, whereas over-expression in vitro is able to confer protection against OS.
Deregulation of this protein is also observed in human ALS and additional mouse models of in neurodegeneration. Despite the apparent high level of conservation of Oxr1-related proteins, virtually nothing is known about their function in vivo. This proposal will establish an independent research programme to understand the role of Oxr1 and related proteins as part of novel pathways that provide protection against both OS and neurodegeneration.

Preliminary data I have generated has identified proteins that interact with Oxr1 in neurons; significantly, a number of these binding partners are mutated in neurodegenerative disease. Therefore, using a combination of mutational and biochemical analysis the relationship of these interactions to neuronal cell death will be investigated . Studies will also focus on the role of Oxr1 in mitochondria, examining the significance of this localisation to the control of the OS response. This will be complemented by in vivo studies in the mouse to to determine whether the loss or disruption of Oxr1-related proteins is critical for CNS function.

Using the latest techniques in molecular genetics and in vivo modelling this project has major translational opportunities and will provide an excellent opportunity to answer one of the key questions in neurodegenerative research.

Fields of science (EuroSciVoc)

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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

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ERC-2012-StG_20111109
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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.

ERC-SG - ERC Starting Grant

Host institution

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
EU contribution
€ 1 328 956,00
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.

No data

Beneficiaries (1)

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