Mutations in one of two transcription factors, ZNF469 and PRDM5, result in brittle cornea syndrome (BCS), a rare genetic disease in which patients have abnormally thin corneas which can spontaneously rupture leading to blindness and eye enucleation.
Following our discovery of PRDM5 as the second BCS gene we have shown that the expression of several components of the extracellular matrix is adversely affected and that an epigenetic mark is dysregulated in the disease.
This PhD project will continue this research and further define the role of epigenetic regulation of PRDM5 target genes in corneal development and disease. In addition to having access to tissue and cell lines from BCS patients the successful candidate will use a Prdm5 knockout zebrafish model to study corneal development and the progression of any associated phenotype.
The project will be conducted within the Institute of Human Development, one of the UK’s leading centres for genetic research. The successful candidate will benefit from training in several cross-cutting skills, combining PCR, RT-PCR, qPCR, immunoblotting, immunofluorescence, histochemistry, expression microarray, pull-down, co-immunoprecipitation, bioinformatics and zebrafish handling.
Candidates are expected to hold a minimum upper-second (or equivalent) undergraduate degree in genetics or a related biomedical/biological science. A Masters qualification in a similar area would be an advantage as would experience of human genetics, epigenetics and/or molecular biology techniques.
This 3-year full-time PhD is open to candidates able to provide evidence of self-arranged funding/sponsorship. Annual fee rates for this project, due to commence from July 2016 onwards, are:
*UK/EU nationals: £18, 500
Non-EU nationals: £31, 500
There is a potential to start in January 2016 if this suits the successful candidate.
Please direct applications in the following format to Dr Forbes Manson ([email protected]
• Academic CV
• Official academic transcripts
• Contact details for two suitable referees
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date
• Evidence of funding.
Any enquiries relating to the project and/or suitability should be directed to Dr Manson. Applications are invited on an on-going basis but early expression of interest is encouraged.
Rohrbach M, Spencer HL, Porter LF, Burkitt-Wright EM, Bürer C, Janecke A, Bakshi M, Sillence D, Al-Hussain H, Baumgartner M, Steinmann B, Black GC, Manson FD, Giunta C. ZNF469 frequently mutated in the brittle cornea syndrome (BCS) is a single exon gene possibly regulating the expression of several extracellular matrix components. Mol Genet Metab. 2013 109:289-95.
Burkitt Wright EM, Porter LF, Spencer HL, Clayton-Smith J, Au L, Munier FL, Smithson S, Suri M, Rohrbach M, Manson FD, Black GC. Brittle cornea syndrome: recognition, molecular diagnosis and management. Orphanet J Rare Dis. 2013 8:68
Burkitt Wright EM, Spencer HL, Daly SB, Manson FD, Zeef LA, Urquhart J, Zoppi N, Bonshek R, Tosounidis I, Mohan M, Madden C, Dodds A, Chandler KE, Banka S, Au L, Clayton-Smith J, Khan N, Biesecker LG, Wilson M, Rohrbach M, Colombi M, Giunta C, Black GC. Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance. Am J Hum Genet. 2011 88:767-77