About the Project
Wheat accounts for 20% of the calories and protein consumed by humans and is the largest crop in the UK. Despite substantial yield increases during the green revolution, yields have now plateaued and are susceptible to decline due to extreme weather patterns. Wheat breeding is a numbers game; the more crosses generated, the greater the chance the breeder has of generating useful combinations of genes (alleles) that lead to a desired phenotype. However, breeding is dependent on the frequency and distribution of crossovers (CO) that are few in number (1-3 per chromosome pair) and skewed towards the chromosome ends. CO initiation sites are not limited in the genome by location or number, but only ~2% mature into actual COs. Therefore, new approaches are needed to increase COs in cereal crops and improve the efficiency of breeding programmes.
In humans, mutations in the RECQ genes, Bloom’s syndrome helicase (BLM) and Werner’s helicase (WRN) are associated with premature ageing and early onset of cancer1. RECQs are conserved throughout eukaryotes and repair DNA by homologous recombination. In Arabidopsis thaliana, the duplicated RECQ4a/RECQ4b genes are the BLM orthologues2 and function redundantly as anti-recombinases during meiosis and by mutating these genes increased COs ~6.2-fold3. A WRN ortholog is not present in Arabidopsis, but we have recently identified one in wheat (RECQ7)4, as well as the BLM ortholog, RECQ4. We have determined that RECQ7 is a pro-CO factor, and RECQ4 is an anti-CO factor, so the two proteins may act antagonistically in processing DNA recombination intermediates down different repair pathways. We have generated knockout mutants of RECQ4 as well as wheat RECQ7 overexpression lines tagged with fluorescent proteins. The mutants and overexpressing lines require analysis as well as determining the mechanism behind altered CO patterns. We will use state-of-the-art super-resolution fluorescence microscopy in conjunction with immunolocalisation and a panel of antibodies developed in the lab that target specific proteins in the CO pathway. Using this approach we will be able to determine the spatio-temporal dynamics of recombination protein loading on meiotic chromosomes. We will also utilise a genomic approach to monitor CO frequency and distribution either through molecular markers or by whole genome skim-sequencing. As part of the training and to gain a fundamental insight into the function of the RECQ helicases, budding yeast will be employed as a model organism to determine the effect on recombination of RECQ4 and RECQ7 across two different kingdoms. Budding yeast possesses a RECQ4 orthlog (SGS1), but not a RECQ7 ortholog, similarly to Arabidopsis, which may reflect genome size, chromosome structure or chromatin environment. There are three outstanding questions that will be investigated in this PhD project:
Q1. How does RECQ7 function as a pro-recombinase in homologous DNA repair in wheat?
Q2. Does RECQ4 act as an anti-recombinase during meiosis in wheat?
Q3. Can we determine an antagonistic mechanism of action between RECQ4 and RECQ7 using both wheat and budding yeast?
The project will be directly translated into crops as well as providing a fundamental knowledge on homologous DNA repair mechanisms in eukaryotes. You will be trained in all modern techniques in an active research lab, with the opportunity for training in external collaborative labs.
• Those who have a 1st or a 2.1 undergraduate degree in a relevant field are eligible.
• Evidence of quantitative training is required. For example, AS or A level Maths, IB Standard or Higher Maths, or university level maths/statistics course.
• Those who have a 2.2 and an additional Masters degree in a relevant field may be eligible.
• Those who have a 2.2 and at least three years post-graduate experience in a relevant field may be eligible.
• Those with degrees abroad (perhaps as well as postgraduate experience) may be eligible if their qualifications are deemed equivalent to any of the above
• University English language requirementsapply. https://le.ac.uk/study/research-degrees/entry-reqs/eng-lang-reqs/ielts-65
To apply please go to https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp
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