Enhancing meiotic recombination in wheat by modulating RECQ helicases


   Department of Genetics and Genome Biology

This project is no longer listed on FindAPhD.com and may not be available.

Click here to search FindAPhD.com for PhD studentship opportunities
  Dr James Higgins, Dr D Guttery  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

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 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 meiosis1. Arabidopsis does not contain a WRN ortholog, but we have identified one in wheat (RECQ7), that is a pro-CO factor2. 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.  

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 in wheat? 

Techniques that will be undertaken during the project

Super-resolution structured illumination microscopy, immunolocalization, fluorescence in situ hybridisation, PCR, cloning, DNA sequencing

Enquiries

Project Enquiries to [Email Address Removed]

Programme enquiries to [Email Address Removed]

To apply please refer to

https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp


Biological Sciences (4)

Funding Notes

All MIBTP students will be provided with a 4 year studentship.
This includes:
Tuition fees at the UK fee rate*
a tax free stipend which for 2023/4 is £18,622 (2024/25 stipend to be confirmed)
a travel allowance in year 1
a travel/conference budget
a generous consumables budget
use of a laptop for the duration of the programme.
The University of Leicester will provide full overseas fee waivers for the duration of their study to all international students accepted at Leicester. The funder, UKRI, allows us to appoint up to 30% overseas students.

References

1. Séguéla-Arnaud M, Crismani W, Larchevêque C, Mazel J, Froger N, Choinard S, Lemhemdi A, Macaisne N, Van Leene J, Gevaert K, De Jaeger G, Chelysheva L, Mercier R. (2015) Multiple mechanisms limit meiotic crossovers: TOP3α and two BLM homologs antagonize crossovers in parallel to FANCM. PNAS;112(15):4713-8.
2. Gardiner LJ, Wingen LU, Bailey P, Joynson R, Brabbs T, Wright J, Higgins JD, Hall N, Griffiths S, Clavijo BJ, Hall A. (2019) Analysis of the recombination landscape of hexaploid bread wheat reveals genes controlling recombination and gene conversion frequency. Genome Biology 20(1):69.