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The non-coding genome in cardiovascular disease


   Faculty of Biology, Medicine and Health

  ,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Cardiovascular disease is the leading cause of death worldwide. Inherited DNA sequence variants play a role in conferring risk for disease, yet we can only predict the harmful effects of mutations in the protein-encoding portion of a gene. The vast majority of sequence variants associated to disease reside elsewhere in the genome, but it has proven very difficult to understand the importance of these variations and their contribution to biological mechanisms. The aim of this project is to characterize the non-coding functional genome that instructs formation of the outflow tract of the heart and the great vessels. We will analyse available datasets in a developmental time course of human embryogenesis (epigenomic profiling of chromatin features, single cell RNA-seq and ATAC-seq) to map regulatory information on the human genome. Integration with genome-wide association studies (GWAS) will prioritize underlying causal mechanisms and predict cell-type–specific effects of GWAS variants located in non-coding regions. Abnormal development of the outflow tract of the heart and the great vessels can lead to congenital heart disease, and increased risk of cardiovascular disease in adulthood. We expect that the results of this project will lead to the discovery of genetic variants associated to congenital heart disease and clinical phenotypes disease risk, and will eventually expand diagnostic and therapeutic capacities.

1.     Candidates are expected to hold a minimum upper-second (or equivalent) undergraduate degree in bioinformatics or a closely related field. Masters qualification in a similar area would be an advantage as would experience of human genetics and genomics.

2.     For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the PhD title.

3.     For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk


Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website View Website
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website View Website

References

Gerrard DT, Berry AA, Jennings RE, Birket MJ, Zarrineh P, Garstang MG, Withey SL, Short P, Jiménez-Gancedo S, Firbas PN, Donaldson I, Sharrocks AD, Hanley KP, Hurles ME, Gomez-Skarmeta JL, Bobola N, Hanley NA (2020). Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders. Nat Commun 11(1):3920. doi: 10.1038/s41467-020-17305-2.
Gerrard DT, Berry AA, Jennings RE, Hanley KP, Bobola N, Hanley NA (2016). An integrative transcriptomic atlas of organogenesis in human embryos. eLife 2016;5:e15657 DOI: 10.7554/eLife.15657

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