This project will generate epigenetic and immunologic markers existing in whole blood samples that are predictive of clinical outcomes to underpin patient stratification and the selection of targets for drug development.
Through the analysis of whole blood RNAseq obtained from existing samples (500 patients and 100 controls – ongoing) we will determine (a) specific differences in gene expression in PAH from controls; (b) the relationship to non-coding variants from matched WGS patients (eQTL analysis); (c) the relationship to immune cell-type specific expression; (d) and deveop a multivariate classifier to stratify the patient cohort. Differentially expressed genes identified from RNAseq will be mapped to non-coding variants using epigenetic markers from ENCODE. Immune specific signatures from MsigDB will also be used to deconvolute the whole blood RNA signal to get relative proportions of immune cell components. Both the epigenetic and immune associated gene expression will be integrated with SomaLogic protein markers. Gene signatures will be generated using machine learning approaches to determine gene patterns relating to phenotype, treatment response and clinical outcome.
You will participate and develop in the exciting Donald Heath pulmonary hypertension research programme. This multi-disciplinary programme combines clinicians and clinician scientists with biologists, physicists and engineers based at the University of Sheffield and Royal Hallamshire Hospital, Sheffield towards the better understanding of the mechanisms driving Pulmonary Hypertension, and improved patient care. The successful candidate will undertake research towards a PhD in the Department of Infection, Immunity & Cardiovascular Disease, Faculty of Medicine Dentistry & Health. There is 1 fully funded PhD studentship available to work on one of the projects listed here - donaldheath.org/home/current-opportunities/
Interested candidates are encouraged to make contact with the primary supervisor to discuss their application. Further project details and additional Donald Heath PhD application form are available from - donaldheath.org/home/current-opportunities/
Please complete a University Postgraduate Research Application form available here: www.sheffield.ac.uk/postgraduate/research/apply
and a separate Donald Heath PhD application form available here: donaldheath.org/home/current-opportunities/