Objective
The need for mitochondria in the body is ubiquitous yet the shapes these organelles take vary widely across tissues and change rapidly in response to nutrient availability. How and why this occurs is not well understood. Therefore, we propose an interdisciplinary research program that will investigate the molecular basis and metabolic regulation of mitochondrial morphology. Mitochondrial morphology is defined by opposing events of fission and fusion, which must be tightly controlled. We discovered that accelerated mitochondrial fission impairs cardiac metabolism and causes heart failure in mice, revealing an intriguing link between mitochondrial dynamics and metabolism. Seeking to understand how metabolic signals drive mitochondrial fission, we will characterize the inner membrane protein MTP18, whose fission activity is controlled by the PI3K nutrient-signalling pathway. First, we will define the interactome of MTP18 to discover the molecular components of the inner membrane fission machinery. Second, we will investigate the how mitochondrial fission is regulated by PI3K nutrient-signalling pathway the heart, liver, and kidney. We will determine whether cardiac dysfunction, liver cancer, and kidney failure caused by over-active PI3K signalling in the mouse can be rescued by blunting the downstream activity of MTP18 and re-balancing mitochondrial dynamics. Third, we will determine the disease relevance of mitochondrial fission in humans. For the first time, mitochondrial morphology from patient-derived cells will be evaluated in automated, high content screens to identify human mutations that drive imbalanced mitochondrial dynamics in a truly unbiased manner. Genome-wide RNAi screens in these cells will reveal novel modulators of mitochondrial dynamics. Taken together, this work aims to understand the metabolic pathways that control mitochondrial morphology and to develop a new technology to identify yet unknown modulators of mitochondrial dynamics.
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.
- medical and health sciences basic medicine anatomy and morphology
- natural sciences biological sciences cell biology cell signaling
- natural sciences biological sciences cell biology cell metabolism
- natural sciences biological sciences molecular biology molecular neuroscience
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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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
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.
ERC-STG - Starting Grant
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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.
(opens in new window) ERC-2016-STG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75794 PARIS
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.