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Synthesizing Meiotic Crossover Hotspots in Arabidopsis

Objective

The majority of eukaryotes reproduce sexually via meiosis. During meiosis homologous chromosomes pair and undergo reciprocal genetic exchange termed crossover. Meiotic recombination is a major evolutionary force and has a profound effect on patterns of genetic diversity in sexual species. Crossovers distributions are highly non-random and are typically focused in narrow hotspots. Study of hotspots throughout eukaryotes has revealed combinations of genetic and epigenetic factors that contribute to their distributions. In this proposal we will use the extensive genetics and genomics tools available in Arabidopsis to comprehensively dissect hotspot patterning. The strategic aim of the proposal is to use this knowledge to direct de novo hotspots to loci of choice. In the first aim we will use functional genomics to profile the chromosomal distributions of key recombination proteins and test the role of chromatin and higher-order structures in driving these patterns. In the second aim we will study individual hotspots at the fine-scale, to the resolution of individual polymorphisms, using amplification and sequencing of recombinant molecules from gamete DNA. To test genetic versus epigenetic control of hotspots we will use genome-editing to delete hotspot-associated CTT-repeat DNA sequence motifs, in addition to directing DNA methylation in order to epigenetically silence recombination. In the final aim we will use our combined knowledge of hotspot control to implement genome-editing technologies (TALENs & CRISPR-Cas9) during meiosis. This will allow us to rationally control hotspot locations, which will be definitive proof that our models for recombination control are correct. This technology will also accelerate breeding and genome-engineering of our most important crops, where recombination can be limiting. Finally, mapping hotspots will allow us to better understand patterns of natural genetic diversity, including detecting the signatures of selection.

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Keywords

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Programme(s)

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Topic(s)

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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.

ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2015-CoG

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Host institution

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution

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.

€ 1 999 953,00
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN Cambridge
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 1 999 953,00

Beneficiaries (1)

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