Objective
The objectives of this proposal are to determine atomic-resolution structures of mammalian mitochondrial respiratory chain supercomplexes (RCSs) by single particle electron cryo-microscopy (cryo-EM). It has been shown that the large protein complexes of the inner mitochondrial membrane responsible for electron transport from NADH to molecular oxygen (complexes I, III and IV) associate to form three major RCSs: I/III2, III2/IV2 and I/III2/IV. Currently, the physiological role of the RSCs is controversial and poorly understood. Atomic-resolution structures of the RSCs will be essential for fully understanding their physiology. Presently I have generated a 15 Å cryo-EM density map for RCS I/III2/IV from ~10,000 particles purified from Ovis aries mitochondria. Our preliminary data show that in order to push the resolution we will need to improve both the biochemical preparation of the RCS particles as well as the cryo-EM grid preparation. This will be done through systematic biochemical characterisation of the RCSs in different non-disruptive detergents and systematic grid preparation varying grid type and blotting conditions. In addition to RCS I/III2/IV, the structure of RCS I/III2 will be determined. High-resolution cryo-EM data will be collected at the Vienna Biocenter using the FEI Polara 300 mV microscope with Gatan K2 direct electron detector. In order to fully compare the make-up of the different RCSs mass spectrometric analysis will be carried out on the purified samples by our collaborators at the Laboratory for Molecular Biology (LMB). My previous experience in the laboratory of Dr Roderick MacKinnon mainly focused on membrane protein structure determination by X-ray crystallography and NMR spectroscopy. The opportunity to work at the IST Austria with Dr Leonid Sazanov will allow me to learn state of the art cryo-EM techniques, which are positioned to be the future of atomic-resolution structure determination for large macromolecular assemblies.
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 earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences physical sciences optics spectroscopy absorption spectroscopy
- natural sciences biological sciences molecular biology
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2015
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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.
3400 KLOSTERNEUBURG
Austria
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.