A 3-year BHF Studentship is available within the Centre of Cardiovascular Genetics, Department of Medicine, University College London supervised by Professor Philippa Talmud. This studentship, which will commence in October 2008, has been specifically awarded in the area of cardiovascular genetics.

The proposed title of the project is `Genetic architecture of secretory PLA2 (sPLA2) genes and their impact on sPLA2 activity and mass and association with CHD risk.’

Outline of the project: Secretory PLA2 (sPLA2)-IIa, -V and -X, generate free fatty acids and lysophospholipids, precursors of pro-inflammatory mediators, and promote LDL retention. Observational studies have shown association of sPLA2 mass and activity with CAD risk, but there is uncertainty as to whether the link is causal. We have reported that tagging SNPs of PLA2G2A and PLA2G5 show strong association with plasma sPLA2 and CAD risk, and LDL levels, respectively. This PhD proposal will aim to validate the haplotype tSNP association with sPLA2 and CAD traits in three large studies with sPLA2 measures. Precise estimates will be made of the genetic effect on the sPLA2 level and activity, and in vitro assays will be carried out to identify the functional SNPs. Associations of measured sPLA2, PLA2G2A genotype with relevant cardiovascular risk factors will be examined to determine the extent to which genetic analyses may overcome potential confounding. Study of the genetic architecture of other sPLA2 genes clustered on Chr 1 will be undertaken to determine the full extent of the likely genetic contribution to variation in sPLA2 level at this locus. These data will be used to develop genetic tools and determine sample sizes required for gene disease association studies to assess whether the sPLA2-coronary event association is likely to be causal.

The research project will be based on the UCL Bloomesbury campus in Prof.Talmud’s research team that has a major focus on genetic determinants of cardiovascular disease.

The project will involve some research work with Prof Aroon Hingorani (in the Department of Epidemiology), with whom the lab has a long-standing collaboration. The scientific environment is excellent and the Centre for Cardiovascular Genetics, headed by Professor Steve Humphries, has international standing and is part of the British Heart Foundation Laboratories in UCL, which houses one of the largest collection of cardiovascular scientists in the UK and provides access to state-of-the-art communal facilities. More details can be found at http://www.ucl.ac.uk/medicine/cardiovascular-genetics/index.html

This exciting project will provide the successful candidate with broad training and expertise in molecular and cell biology, epidemiology and statistics. Applicants should have a background preferably in genetics, although a broader biological background will be considered. Only UK- or EU- residents should apply as the BHF do not sponsor non-UK or EU PhD fellows.

The work will lead to a PhD and the grant provides a (tax-free) stipend. University fees will be covered.

Only applicants with a good 2.1 or better honours degree will be considered. To apply, please send a letter explaining why you want to become a research student in this field and a CV including the contact details of two referees to Professor Philippa Talmud, Dept. of Medicine, The Rayne Institute, 5 University Street, London WC1E 6JF or by email to [email protected].

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The closing date for applications is Monday, 1st September 2008.