Objective
The project aims at unraveling the molecular pathophysiology of recessive ataxias, a heterogeneous set of severely disabling neurodegenerative disorders due to loss of function of proteins involved either in mitochondrial/metabolic pathways or DNA repair. Friedreich ataxia, the most common form, is due to partial loss of function of frataxin, a mitochondrial protein involved in iron-sulfur cluster (ISC) biogenesis. Furthermore, the rare X-linked sideroblastic anemia with cerebellar ataxia is caused by mutation in ABCb7, an ATP-binding cassette transporter of the mitochondrial inner membrane necessary for cytosolic ISC export. ISC are versatile co-factors of proteins involved in electron transport, enzyme catalysis and regulation of gene expression. The synthesis and insertion of ISC into apoproteins involve complex machineries that are still poorly understood in the mammalian cell. The objectives of this proposal are: 1) to elucidate ISC biogenesis and metabolism in the mammalian cell, with an emphasis on the role of frataxin and ABCb7; 2) to better understand the molecular pathways that are involved in neuronal dysfunction due to defects in mitochondrial ISC metabolism. These objectives will be accomplished by a multidisciplinary approach combining molecular and biochemical approaches to study the ISC assembly machineries, bioinformatic and proteomic studies to identify new Fe-S proteins, the development and pathological analysis of animal and cellular models to dissect the molecular mechanisms, and transcriptomic analysis to uncover the common pathways among recessive ataxias. A specific focus of the proposal will be the involvement of DNA damage response pathways in neuronal dysfunction, as several DNA repair enzymes have recently been identified as Fe-S proteins and thus might be directly affected by frataxin and ABCb7 deficiency. This proposal should lead to the identification of different pathways for therapeutic intervention for these devastating disorders.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine physiology pathophysiology
- medical and health sciences clinical medicine hematology
- natural sciences chemical sciences catalysis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
ERC-2007-StG
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.
Host institution
67404 Illkirch Graffenstaden
France
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.