Enhancing meiotic recombination in wheat by modulating RECQ helicases

Qualification: PhD

Department: Genetics

Application deadline: 31 May 2021

Start date: 27 September 2021

Overview

Supervisors:

Dr James Higgins and Professor Ed Louis

Project description:

Wheat accounts for 20% of the calories and protein consumed by humans and is the largest crop in the UK, but yields have plateaued and are susceptible to decline due to extreme weather conditions. Wheat breeding is a numbers game; the more crosses generated, the greater the chance of generating useful trait combinations. 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, so even with a large number of crosses, desired combinations may not be attained. CO initiation sites are not limited in the genome by location or number, but only ~2% mature into COs, suggesting potential within the system to increase recombination.

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 cancer. RECQs are conserved throughout eukaryotes and repair DNA by homologous recombination. In Arabidopsis thaliana, the BLM orthologues (RECQ4a/RECQ4b) function redundantly as anti-recombinases during meiosis. Arabidopsis does not contain a WRN ortholog, but we have recently identified one in wheat (RECQ7), that is a pro-CO factor. RECQ4 is an anti-CO factor, so the two proteins may function antagonistically in processing DNA recombination intermediates. In wheat we have isolated knockout mutants of RECQ4 and RECQ7 as well as generating RECQ7 overexpression lines that require analysis for altered recombination 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. Molecular markers will also be utilised to monitor recombination frequency. To gain a fundamental insight into the function of the RECQ helicases, budding yeast will also 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 ortholog (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?

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 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.

Funding

Funding

The Studentship provides:

  • 3 Years of stipend at UKRI rates
  • 3 Years tuition fees at UK rates

Entry requirements

Entry requirements

UK Bachelor Degree with at least 2:1 in a relevant subject or overseas equivalent.

The University of Leicester English language requirements apply where applicable.

Informal enquiries

Informal enquiries

Project enquiries to Dr James Higgins jh555@le.ac.uk 

Application enquiries to pgradmissions@le.ac.uk

How to apply

How to apply

To submit your application, please use the Apply button at the bottom of the page and select September 2021 from the dropdown menu.

With your application, please include:

  • CV
  • Personal statement explaining your interest in the project, your experience and why we should consider you
  • Degree Certificates and Transcripts of study already completed and if possible transcript to date of study currently being undertaken
  • Evidence of English language proficiency if applicable
  • In the reference section please enter the contact details of your two academic referees in the boxes provided or upload letters of reference if already available
  • In the funding section please specify that you wish to be considered for the GGB Higgins 2021 studentship
  • In the research proposal section please provide the names of the project supervisors and project title (a research proposal is not required)

Eligibility

Eligibility

This PhD studentship is available to UK/EU applicants only.