Objective
"Cells use sensor pathways compartmentalized in subcellular organelles to recognize stress conditions, including aberrant protein folding, and in response activate gene expression programs aimed at maintaining cell survival and restoring homeostasis. Fine-tuning of the protein-folding environment in organelles like mitochondria is important for adaptive homeostasis and may participate in development of human diseases and ageing. Work in cultured mammalian cells and more recently in Caenorhabditis elegans has highlighted the importance of mechanisms linking perturbations in the protein-folding environment in the mitochondrial matrix to the expression of nuclear genes encoding mitochondrial proteins. This mitochondrial stress pathway is named mitochondrial unfolded protein response. Much of our knowledge regarding the organelle unfolded protein response (UPR) signalling comes from studies of the endoplasmatic reticulum stress response machinery. In contrast, a potential role of mitochondria in UPR pathway is far less defined, and physiologic regulators of this pathway have not been defined.
Here I propose three complementary strategies to identify molecular mechanisms and signalling pathways of the mitochondrial unfolded protein response (UPRmt) under different stress conditions and during ageing. My laboratory has experience in using transgenic mice and C. elegans as experimental tools and both of these powerful model systems will be used in this project.
Specific aims of this proposal are:
Aim 1. To identify specific substrates of UPRmt
Aim 2. To define mechanisms regulating mammalian UPRmt
Aim 3. To elucidate the role of UPRmt signalling in ageing"
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 biochemistry biomolecules proteins protein folding
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- medical and health sciences basic medicine physiology homeostasis
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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.
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.
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
50937 Koeln
Germany
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.