Objective
To elucidate the biological role of the mitochondrial outer membrane (MOM), I propose to determine structures and functions of integral MOM protein complexes at atomic resolution, involving the three proteins VDAC, Bax and Sam. These are key elements of vital cellular functions: the regulation of bioenergetics, mitochondrial biogenesis, apoptosis and cancer. Our results will give new insights into the biology of eukaryotes and will open up new avenues for pharmaceutical applications.
My research group will pursue the following objectives:
A. Determination of the structures of the VDAC–NADH, the VDAC–cholesterol, and the VDAC–hexokinase complexes. These structures will provide the molecular basis for metabolism regulation by the voltage-dependent anion channel VDAC and for its role in the “Warburg effect”, a crucial step of cancerogenesis of most cancers.
B. Determination of the structure and insertion mechanism of the Bax transmembrane-pore and its formation and inhibition by drug candidates. The formation of the Bax pore in the MOM is the final, deadly step in mitochondrial apoptosis and the structure will thus elucidate a key regulatory element of multicellular organisms.
C. Determination of the structure and function of the sorting and assembly machinery (Sam), including its core protein, the beta-barrel protein Sam50, and its interactions with substrates. These results will explain the insertion of membrane proteins during the biogenesis of the MOM, an essential for eukaryotic life.
Structure determinations of membrane proteins are still major technical challenges and so far, with VDAC, only a single structure of an integral MOM protein is known, determined by the present author and colleagues. While bringing groundbreaking biological insights, our research will further extend the methodological approaches for membrane protein structure determination by nuclear magnetic resonance (NMR) spectroscopy to a new level.
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.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences molecular biology structural biology
- natural sciences physical sciences optics spectroscopy
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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-2011-StG_20101109
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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
4051 Basel
Switzerland
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.