Project description
A genetic tool for studying mitochondrial DNA
Our mitochondria contain a separate genome (mtDNA) which we inherit from our mothers and has been associated with several metabolic diseases. Various technological obstacles have limited the study of mtDNA and hence of many aspects of its biology. The EU-funded Mito-recombine project has developed innovative genetic tools that allow the manipulation and analysis of mtDNA in the Drosophila fruit fly. Researchers are interested to delineate the process of homologous recombination of mtDNA and build a genetic tool for further functional studies. This tool will pave the way towards a better understanding of the implications of mtDNA mutations in disease.
Objective
Mitochondrial DNA (mtDNA) is a multi-copy genome that works with the nuclear genome to control energy production and various cellular processes. To date, disorders associated with mutations in mtDNA are among the most common genetically inherited metabolic diseases1. However, our knowledge regarding many aspects of mtDNA biology remains limited, and we know even less about how it influences development and organismal traits. This is largely due to our inability to manipulate mtDNA. Recently, a colleague and I developed novel genetic tools in Drosophila that allowed us to isolate animal mitochondrial mutants for the first time, and to create heteroplasmic organisms containing two mitochondrial genotypes2,3. These advances make Drosophila a powerful system for mtDNA studies. Importantly, I showed that Drosophila mtDNA could undergo homologous recombination. Furthermore, I established a system to induce recombination at specific sites and select for progeny containing only the recombinant genome4. Thus, my work has demonstrated the existence of recombination in animal mitochondria, and opens up the possibility of developing a recombination system for functional mapping and manipulating animal mtDNA. Here I propose to 1) identify components of the mitochondrial recombination machinery by a candidate RNAi screen; 2) develop a recombination toolkit to map trait-associated mtDNA sequences/SNPs; and 3) build a site-directed mutagenesis system by establishing robust ways to deliver DNA into fly mitochondria. Given the essential functions of mitochondria and their involvement in incurable diseases, the genetic tools developed in this proposal will transform the field by making it possible to link mtDNA variations to phenotypic differences and introduce specific mutations into mtDNA for functional studies at organismal level. These advances will open many possibilities to accelerate our understanding on how mtDNA impacts health, disease and evolution.
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 genetics DNA
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics genomes
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Programme(s)
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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)
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Topic(s)
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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
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2018-STG
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B15 2TT Birmingham
United Kingdom
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