Objective
Here, I propose to study the structure and mechanisms of the cellular machineries mediating the shape and dynamics of the mitochondrial inner membrane (IM). The mitochondrial IM contains membrane invaginations called cristae. These are connected by tubular openings, the crista junctions, to the remaining IM. Mitochondrial shape constantly changes due to membrane fission and fusion events, and a balance of both processes is required for proper functioning of mitochondria. Abnormal mitochondrial shape and altered dynamics are associated with severe diseases, such as cancer and neurodegeneration.
Sourcing my group’s expertise in dynamin superfamily GTPases, I wish to understand the molecular mechanisms of how OPA1 can achieve mitochondrial IM fusion and cristae formation. To this end, the X-ray crystallographic structure of OPA1 will be determined and complemented by a comprehensive biochemical characterization. Cell-based assays will be employed to decipher the exact mechanism by which OPA1 carries out its two functions and how specific mutations in OPA1 disturb these processes and, thereby, induce human disease.
The multiprotein MINOS complex was recently shown to be involved in the formation of crista junctions. I propose to explore the architecture of the MINOS complex. To this end, X-ray crystallographic structures of single components, subcomplexes and, eventually, the complete complex will be determined. Based on these structures, the mechanism of MINOS in mitochondrial membrane remodeling and crista junction formation will be dissected using a structure-based mutagenesis approach.
Components of MINOS were shown to interact with OPA1 and with the sorting and assembly machinery (SAM) of the outer mitochondrial membrane. The interactions of MINOS with OPA1 and SAM will be biochemically mapped and structurally characterized. To understand their functions, the effect of disrupting mutations on crista junction formation and mitochondrial dynamics will be explored.
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
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
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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-2013-CoG
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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
13125 Berlin
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.