Objective
Gene duplication followed by sequence divergence is recognized as a key mechanism in evolution to generate functional innovations and enrich the complexity of genetic networks. Though gene duplication is frequently observed, the ensuing process leading to functional differentiation among gene duplicates remains obscure. Lack of this critical information has limited not just our fundamental understanding of protein evolution, but the success in engineering enzymes for industrial applications and our ability to predict evolution, for instance, mutations accessible to pathogens against antibiotic treatments. To fill this knowledge gap, I propose an integrative approach to bring mechanistic insights into the functional diversification among flavoprotein disulfide reductases (FDRs), namely glutathione reductases, lipoamide reductases, soluble transhydrogenases, and mercuric reductases. Diverged before the split between prokaryotes and eukaryotes, these ancient gene duplicates now participate in distinct branches of cell metabolism but maintain remarkable sequence and structure conservation. Furthermore, they exhibit the ability to turn over secondary substrates (i.e. promiscuity). I will address the evolutionary history, functional divergence, and mechanistic basis of promiscuity of FDRs, and explore their utility for biotechnology through the following steps: (1) phylogenetic reconstruction of ancestral FDRs to examine the functional shift from ancestral to extant FDRs, (3) directed evolution of one or more FDRs toward novel functions, (4) replaying gene duplication and functional divergence of FDRs in real-time by microbial evolution experiments. This project is aimed at answering core questions in molecular evolution and exploring the utility of promiscuous enzymes by bringing the applicant’s expertise in evolutionary analysis and microbial genetics to the host group that masters enzymology, chemical biology, and cutting-edge directed evolution techniques.
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.
- humanities history and archaeology history
- natural sciences biological sciences cell biology cell metabolism
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences molecular biology molecular evolution
- 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.
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.
FP7-PEOPLE-2011-IIF
See other projects for this call
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.
Coordinator
CB2 1TN Cambridge
United Kingdom
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.