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Alpha-defensin haplotypes and IgA nephropathy risk


School of Life Sciences

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Prof J A L Armour , Prof O Hanotte Applications accepted all year round Self-Funded PhD Students Only

About the Project

The human alpha-defensin genes DEFA1 and DEFA3 encode short antimicrobial peptides that are important components of the innate immune system, and are subject to copy number variation (CNV) with individuals having between 3 and 18 copies. Association studies have demonstrated that genetic variants near to DEFA1 and DEFA3 are associated with the serious kidney disease IgA nephropathy. In collaboration with groups in Guangzhou and Singapore, Prof Armour’s group have shown that the association signal can be attributed to the CNV region, with two specific variants implicated: one variant provides protection against IgA nephropathy and is specific to Asian populations; the second variant predisposes to IgA nephropathy in both Europeans and Asians. The structures of the variants implicated in IgA nephropathy, and the features leading to the associations with disease, are currently unknown. This project will combine detailed analysis of publicly available sequence data (from the 1000 Genomes Project), novel approaches to long-read sequencing (using Nanopore devices) and examination of datasets from affected individuals to understand how alpha-defensin variants predispose to IgA nephropathy. This project would give the student experience in the analysis of genetic variation relevant to disease, high-resolution characterisation of copy number variation, and manipulation of large datasets.

The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.

Funding Notes

Home applicants should contact the supervisor to determine the current funding status for this project. EU applicants should visit the Graduate School webpages for information on specific EU scholarships http://www.nottingham.ac.uk/GraduateSchool/index.aspx. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University http://www.nottingham.ac.uk/studywithus/international-applicants/scholarships-fees-and-finance/index.aspx.

References

Ai, Z., Li, M., Liu, W., Foo, J.N., Mansouri, O., Yin, P., Zhou, Q., Tang, X., Dong, X., Feng, S., Xu, R., Zhong, Z., Chen, J., Wan, J., Lou, T., Yu, J., Zhou, Q., Fan, J., Mao, H., Gale, D., Barratt, J., Armour, J.A., Liu, J. and Yu, X. (2016). Low α-defensin gene copy number increases the risk for IgA nephropathy and renal dysfunction. Science Translational Medicine. 8, 345ra88.

Black H.A., Khan, F.F., Tyson, J. and Armour, J.A.L. (2014) Inferring mechanisms of copy number change from haplotype structures at the human DEFA1A3 locus. BMC Genomics 15, 614
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