Objective
Spinal and bulbar muscular atrophy (SBMA) is one of nine polyglutamine diseases and is caused by expansion of CAG in the androgen receptor (AR) gene. Despite the widespread distribution of polyglutamine proteins in the central nervous system, specific populations of neurons are vulnerable in each disease, suggesting that selective neuronal vulnerability arises from intrinsic properties of the mutant proteins. The central hypothesis of this proposal, based on preliminary data, is that neurotoxicity is influenced by protein context, aberrant protein-protein interactions and cell context. The applicant will test this hypothesis at the Italian Institute of Technology (Genoa, Italy) in collaboration with the National Institutes of Health (MD, USA), from where she returns, and the St Jude Children’s Hospital (TN, USA), by pursuing the following Aims: 1) To characterize the impact of phosphorylation on mutant AR toxicity. The applicant will test the hypothesis that protein kinase A reduces mutant AR toxicity by a mechanism that involves modification of mutant protein phosphorylation in SBMA cells. 2) To characterize the role of FOXO in polyglutamine disease. The applicant will test the hypothesis that IGF-1/Akt signalling promotes neuronal survival through inhibition of FOXO in mouse models of SBMA. 3) To determine the impact of tissue-specificity of mutant protein expression. The applicant will test the hypothesis that expression of the disease protein in a tissue-specific fashion influences SBMA pathogenesis. The applicant will use the LoxP-Cre system. Transgenic LoxP-AR mice have been generated in Memphis. This collaboraive project between the host Institution, the Italian Institute of Technology and the Institution from which the fellow returns, NIH USA, and the St Jude Children Hospital, USA, is expected to provide novel insights into the mechanisms of disease pathogenesis in neurodegenerative diseases and to contribute to the transfer of knowldge to Europe.
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.
- natural sciences biological sciences neurobiology
- medical and health sciences clinical medicine oncology prostate cancer
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
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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-2009-RG
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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.
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
16163 Genova
Italy
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.