Genome-wide association studies (GWAS) have successfully mapped the loci underlying many economically important phenotypes and their underlying molecular causes, such as gene expression. The FarmGTEx consortium has recently identified quantitative trait loci that regulate gene expression (eQTLs) genome-wide across various livestock species, including cattle, pig and chicken. However, the vast majority of these loci are found in noncoding regions beyond the borders of currently annotated gene bodies which makes them challenging to interpret.
It is often assumed that those noncoding genomic regions which have been conserved across evolution are most likely to contain functionally important sequences but our recent work has revealed that – at regulatory loci known as promoters – it is those sequences which turn over between species which are actually most likely to harbour regulatory variants. Therefore, it is of much interest to understand how the variants we see today came to be and how evolutionary processes contribute to the genetics of complex phenotypes by integrating molecular and evolutionary biology.
This project will investigate the role of regulatory conservation and divergence between species and breeds on a genome-wide scale. The student will first reconstruct the evolutionary trajectories of eQTLs which have already been identified across the cattle, pig and human genomes. These data will be used to investigate the nucleotide substitution patterns at eQTLs and thereby identify the mutational mechanisms underlying their conservation/divergence. Simultaneously, publicly available data from the FANNG consortium will be used to characterise the epigenetic modifications at these loci and determine how epigenetic changes correlate with changes in eQTL content across species.
Whole-genome sequence alignments will later be used to test whether these events are the subject of natural selection. The student will investigate whether any evolutionary pressures are apparent only at the regulatory variant itself or extend throughout the broader locus. Once those variants which have experienced selection have been identified, the student will characterise their genomic and transcriptomic features (e.g. genetic architecture, contribution to complex trait variation). These analyses will reveal how such variation is created and maintained and how genetic and/or epigenetic manipulations can be used to manipulated to improve complex traits such as livestock productivity, welfare and health.
The student will become proficient in the integration of big ‘omics’ and population-scale genetics datasets using a range of computational and statistical tools. The student will be trained in various bioinformatics techniques required to study genomic variation.
Introduction to EASTBIO
The UKRI BBSRC East of Scotland Doctoral Training Partnership (EASTBIO DTP) comprises the Universities of Edinburgh, Aberdeen, Dundee, Stirling, St Andrews, along with SRUC, IBioIC, the James Hutton Institute and the Moredun Research Institute as Full Partners. The Cool Farm Alliance and SULSA are Associate Partners.
For the DTP3 funding, the EASTBIO programme will award standard 4-year Studentships and 4-year Collaborative Studentships - collaborative with industrial/non-academic organisations - to start in October 2022. For DTP3 we have developed a part-time doctoral study route, plus a flexible model for industry partnering that offers three routes for industrial studentships.
Application procedure
This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP) http://www.eastscotbiodtp.ac.uk/how-apply-0
This opportunity is open to UK and international students and provides funding to cover stipend and UK level tuition fees. The University of Edinburgh will cover the difference between home and international fees meaning that the EASTBIO DTP will offer fully-funded studentships to all appointees. However there is a cap on the number of international students the DTP can recruit. It is therefore important for us to know from the outset which fees status category applicants will fall under when formally applying for entry to our university.
Please refer to UKRI and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.
EASTBIO Application and Reference Forms can be downloaded via http://www.eastscotbiodtp.ac.uk/how-apply-0
List of documents to be submitted to [Email Address Removed] by 16 December 2021
- EASTBIO Application Form
- EASTBIO Reference Form
- Transcript of Degrees to date in PDF format
- CV
Following interview, the selected candidate will need to apply and be accepted for a place on the Usher Institute Population Health Sciences PhD programme. Details about the PhD programme can be found here: https://www.ed.ac.uk/studying/postgraduate/degrees?r=site/view&id=698
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