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ERA-CAPS 13 Delineating the crossover control networks in plants (DeCOP)

Reference	BB/M004902/1
Principal Investigator / Supervisor	Professor Chris Franklin
Co-Investigators / Co-Supervisors	Dr Eugenio Sanchez-Moran
Institution	University of Birmingham
Department	Sch of Biosciences
Funding type	Research
Value (£)	422,537
Status	Completed
Type	Research Grant
Start date	01/04/2014
End date	30/09/2017
Duration	42 months

Abstract

Meiotic recombination is initiated by programmed DNA double-strand breaks (DSBs). The positions of the DSBs define loci of mutual genetic exchange. However, in a single meiotic cell only a small subset of DSBs are destined to form genetic crossovers (COs), while the remainder are repaired via non-CO pathways. CO formation itself is subject to stringent control, which ensures that each homologue pair receives at least one obligate CO. A phenomenon known as CO interference then ensures that most (~85%) additional COs do not occur in an adjacent chromosomal region. As a result multiple COs are spaced well apart along the homologues. Understanding the factors that control DSB formation and processing to form COs is of fundamental scientific interest, moreover this knowledge will have important implications for manipulating meiotic recombination in crop plants. In recent years meiosis research in plants has largely focussed on the identification of meiotic genes/proteins involved in recombination pathways or the organization of the chromosome axes and synaptonemal complex. Although these studies clearly demonstrate the importance of these proteins, it remains mostly enigmatic how their activities are coordinated to ensure the controlled formation of COs. This collaborative project seeks to shift emphasis to focus on how recombination, chromosome organisation and remodelling are orchestrated to control the frequency and distribution of COs. Specifically, we propose to 1) perform an innovative screen to identify novel factors that modulate CO formation and interference, 2) investigate the role of chromosome axis-associated proteins in CO maturation and interference, 3) determine the role of (ATM/ATR mediated) phosphorylation in coordinating meiotic DNA repair and CO formation and 4) to identify proteins involved in the final step of CO formation. These studies will significantly enhance our understanding of the networks that govern CO formation in plants.

Summary

Meiosis is a specialized type of cell division required for sexual reproduction. It ensures the reduction of the genome and the recombination of maternal and paternal chromosomal segments prior to the formation of generative cells. Understanding the factors that control the initiation of recombination and processing recombination intermediates to form crossovers is of fundamental scientific interest, moreover this knowledge will have important implications for manipulating meiotic recombination in crop plants. In recent years meiosis research in plants has largely focussed on the identification of meiotic genes/proteins involved in recombination pathways or the organization of the chromosome axes and the synaptonemal complex, a specialized proteinaceous structure transiently formed during meiosis between the pairs of homologous chromosomes. Although these studies clearly demonstrate the importance of these proteins, it remains largely enigmatic how their activities are coordinated to ensure the controlled formation of crossovers. Key questions relate to how recombination is controlled such that each pair of homologous chromosomes receives at least one genetic crossover and how any additional crossovers are prevented from occurring in an adjacent chromosomal region; a phenomenon termed crossover interference. This collaborative project seeks to shift emphasis to focus on how recombination, chromosome organisation and remodelling are orchestrated to control the frequency and distribution of crossover events. Specifically, we seek to identify the protein networks that determine the fate of the individual DNA double-strand breaks that initiate recombination and establish when CO interference is established. We aim to identify novel factors that modulate crossover formation and interference; to investigate the role of chromosome axis-associated proteins in CO maturation and interference, to determine the role of protein phosphorylation in coordinating meiotic DNA repairand crossover formation; to identify proteins involved in the final step of crossover formation. We anticipate the factors and processes studied in the project will significantly enhance our understanding of the networks that govern crossover formation in plants. We therefore believe that our findings will strongly stimulate future crop breeding programmes.

Impact Summary

Who will benefit The proposed project fulfils several BBSRC strategic aims: "maintaining world-class UK Bioscience by supporting the best people and best ideas", "providing skilled researchers needed for academic research". It has particular relevance to BBSRC's strategic priorities in regard to crop breeding/food security. In addition to academic beneficiaries we have strong links with plant breeding companies such as KWS, Sesvanderhave, Limagrain, Rijk Zwaan. We regularly participate in annual meetings of the UK-Brassica Research Community (UK-BRC) and Monogram, and international conferences eg PAG where we have presented talks. We propose to continue this as these meetings provide an ideal forum to present our work to wider crop research community and to plant breeders. Realizing the importance of scientific outreach we have also established links with NIAB Experimental Farm, Cambridge and Birmingham Thinktank Science museum. We intend that the PIs and staff appointed on the ERA-CAPs DeCOP project will work in close collaboration with partners and doctoral students in an EU funded Marie-Curie project (COMREC - PITN-GA-2013-606956 coordinated by Franklin) on a number of outreach events aimed at the general public and end-users. This will include: Developing information pack for schools explaining the role of meiosis research and plant breeding in delivering Food Security for the 21st Century; school visits, University open days; a Thinktank Meet the Scientist Event: Breeding crops to meet the challenges of the 21st century; and dissemination event at NIAB Experimental Farm aimed at end-users. How will they benefit? Plant breeding is reliant on the creation of genetic variation that arises during meiotic recombination. Important challenges remain fro plant breeders. For example, it has been known for some time that large segments of chromosomes in crop species, notably cereals, rarely recombine. This is a serious barrier to the breeding of lines with new traits.Thus there is a real need to understand the major factors that control the frequency and distribution of meiotic crossovers during recombination. The work in ERA-CAPs DeCOP will provide fundamental knowledge that can be directly incorporated in on-going work on crop species in the partners laboratories and by the plant breeding companies. We are already making in-roads into the development of strategies for manipulating recombination (eg Higgins et al 2012 Plant Cell doi: 10.1105/tpc.112.102483) and would anticipate these can be harnessed by breeders over the next few years following further refinement. Dr Kim Osman the named postdoc on the grant will develop and acquire additional skills to match her extensive experience in molecular cytogenetics. This will include developing live imaging; application of super-resolution microscopy and developing ChIP seq on meiocytes. She will take an active role in the engagement activities providing her with experience in interacting with the general public and plant breeding industry.

Committee	Research Committee B (Plants, microbes, food & sustainability)
Research Topics	Plant Science
Research Priority	X – Research Priority information not available
Research Initiative	ERA-NET on Coordinating Action in Plant Sciences (ERA-CAPS) [2013-2014]
Funding Scheme	X – not Funded via a specific Funding Scheme

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