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Chromatin and recombination landscapes in the hexaploid wheat genome

Supervisor: Dr Ian Henderson

Industrial Partner: KWS UK Ltd

Cambridge BBSRC DTP Industrial CASE (iCASE)

Project:

Meiotic recombination creates genetic diversity in the progeny of sexually reproducing species. For example, reciprocal exchange between homologous chromosomes (known as crossover) creates novel combinations of genetic variation. The variation-generating processes acting during meiosis remain a major tool for crop improvement, whereby useful characteristics from different backgrounds can be combined. Bread wheat is a major crop in the UK and globally, where meiotic recombination during breeding remains an essential tool for variety improvement. However, the wheat genome is extremely large (17 gigabases) and shows highly skewed recombination distributions, with most crossovers occurring in the distal regions of the chromosomes. This severely limits the ability of breeders to utilise variation located in the central regions of the chromosomes. Therefore, developing tools and technologies to control recombination in wheat has direct relevance for food security.

In this project the student will use chromatin immunoprecipitation (ChIP) followed by high throughput sequencing to profile the distribution of euchromatic and heterochromatic chromatin modifications throughout the wheat genome. These distributions will be related to high-resolution genetic maps from genotypes that differ in their genetic map lengths. These experiments will be conducted in backgrounds of interest to KWS and the student will identify chromatin patterns that correlate with altered frequencies and patterns of recombination. The recent public release of a high quality reference wheat genome assembly makes this project feasible and timely.

New reverse genetic resources (e.g. TILLING, CRISPR-Cas9) are available that allow genes of interest to be disrupted in bread wheat. To functionally investigate the role of chromatin on recombination the student will isolate mutations in epigenetic regulators. These mutants will be profiled using ChIP-seq in order to characterise how chromatin is altered genome-wide. Finally, these mutants will be used to measure effects on number and distribution of recombination events during meiosis.

This project will provide the student with advanced training in wheat genetics and genomics. They will generate data of basic importance for understanding wheat genome function and evolution. They will gain experience in wheat genetics relevant to both academic and industrial scientific contexts.

Industrial Partner:

KWS UK Ltd. is focused on breeding winter and spring wheat and barley and currently have over 40% market share in the UK for these crops. The KWS parent company (KWS SAAT SE) is one of the four world leading plant breeding companies, and has been breeding crops for temperate climates for more than 150 years. In fiscal year 2014/15, the KWS Group and its 60 subsidiaries generated net sales of over €1.1 billion. The annual expenses for R&D amount to around 15% of KWS’ net sales which represents a significant reinvestment in future productivity. As a result, across all crops, KWS is able to provide farmers with almost 300 new, higher-yielding market approvals every year.

The student will visit KWS for their placement and will have the opportunity to work and interact with members from all KWS departments, providing insight into the workings of a plant breeding company. Through the collaboration they will have access to the resources available at KWS UK in a more project specific manner. There will also be opportunity for the student to attend relevant internal scientific meetings and be part of the student cohort that exists within the KWS group.

To ensure that the training needs of the student are met, KWS will communicate closely with Dr Ian Henderson, the academic supervisor, to develop a program of work. KWS UK are very proud of their excellent record for hosting students and have acted as an industrial partner with an extremely high success rate in seeing PhD students to the completion of their qualifications and successful future careers in the agricultural sector.

Applications & Deadline:

Interested candidates should apply through Cambridge Graduate Admissions: http://www.graduate.study.cam.ac.uk/courses/directory/blpspdpsc by 01/01/2018. Eligibility is restricted to UK and EU residents. Enquiries can also be made directly to Dr Henderson irh25@cam.ac.uk.

The project will commence October 2018 and is 4 years in length.

The studentship will cover a stipend at the standard Research Council rate (£14,553 per annum for 2017/18), research costs and tuition fees at the UK/EU rate, and is available for UK and EEA students who meet the UK residency requirements. Students from EEA countries who do not meet the residency requirements may still be eligible for a fees-only award. Further information about eligibility for Research Council UK funding can be found at the following website:

The studentship is part of the BBSRC DTP Programme (http://bbsrcdtp.lifesci.cam.ac.uk/). The student will complete tailored training courses, a PhD and have the opportunity to spend time with the industrial Partner, KWS UK Ltd. The Programme organises a number of events, training courses and workshops to foster cohort development, skills enhancement and networking opportunities.

Relevant Publications:

  1. Choi, K., Zhao, X., Kelly, K.A., Venn, O., Higgins, J., Yelina, N., Hardcastle, T., Ziolkowski, P., Copenhaver, G.P., Franklin, C. McVean, G.A. and Henderson, I.R. (2013) ‘Meiotic crossover hotspots overlap with H2A.Z nucleosomes at Arabidopsis gene promoters.’ Nat. Genet. 45: 1327-1336.
  2. Yelina, N.E., Lambing, C., Hardcastle, T.J., Zhao, X., Santos, B. and Henderson, I.R. (2015) ‘DNA methylation epigenetically silences crossover hotspots and controls chromosomal domains of meiotic recombination in Arabidopsis’ Genes Dev doi/10.1101/gad.270876.115.
  3. Ziolkowski, P.A., Berchowitz, L.E., Lambing, C., Yelina, N.E., Zhao, X., Kelly, K.A., Choi, K., Ziolkowska, L., June, V., Sanchez-Moran, E., Franklin, C., Copenhaver, G.P. and Henderson, I.R. (2015) ‘Juxtaposition of heterozygous and homozygous regions causes reciprocal crossover remodeling via interference during Arabidopsis meiosis’ eLife 4: e03708.
  4. Yelina, N.E., Ziolkowski, P.A., Miller, N., Zhao, X., Kelly, K.A. Munoz, D.F. Mann, D.J., Copenhaver, G.E. and Henderson, I.R. (2013) ‘High throughput measurement of meiotic crossover frequency and interference via flow cytometry of fluorescent pollen in Arabidopsis thaliana.’ Nat. Protoc. 8: 2119-2134.
  5. Choi, K. and Henderson, I.R. (2015) ‘Meiotic recombination hotspots – a comparative view. Plant J. 83: 52-61.
  6. Dreissig S, Fuchs J, Cápal P, Kettles N, Byrne E, Houben A (2015) Measuring Meiotic Crossovers via Multi-LocusGenotyping of Single Pollen Grains in Barley. PLoS ONE 10(9): e0137677.doi:10.1371/journal.pone.0137677