Objective
The removal of misfolded proteins is an essential process in all cells. Failure to dispose of such proteins often results in disease. A particularly intriguing process serves to discard misfolded proteins from the endoplasmic reticulum (ER). The ER does not itself degrade proteins, so machinery has evolved that moves misfolded proteins into the cytosol where they can be degraded by the proteasome. This retro-translocation process is called ERAD (for ER-associated protein degradation). By comparison with other membrane translocation processes, the mechanism of ERAD is poorly understood. How are misfolded proteins distinguished from folding intermediates? How are proteins moved across the membrane? How is the energy for membrane translocation provided? To answer these fundamental questions I will use a combination of in vitro reconstitution experiments with purified proteins from S. cerevisiae and experiments in intact yeast cells. It appears that some ERAD components have been adapted to function in protein translocation in a very different setting. Many parasites like the malaria causing P. falciparum contain a plastid-like organelle, called the apicoplast. It is the site of several metabolic pathways essential for the parasite’s survival, and thus an important drug target. Like other organelles of endosymbiotic origin, the apicoplast lost most of its genetic information and has to import proteins. This is a particularly challenging endeavour because four membranes surround the apicoplast. It is thought that symbiont specific ERAD-like machinery (SELMA) mediates proteins translocation across the second-outermost membrane. However, not much is known about SELMA. What is its molecular composition? Which aspects of SELMA are conserved in comparison to the classical ERAD machinery? I will address these important questions using a completely novel combination of biochemical and genetic approaches.
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 health sciences infectious diseases malaria
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences cell biology
- natural sciences biological sciences biochemistry biomolecules proteins protein folding
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
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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-2015-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.
80539 MUNCHEN
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.