Download Nociceptin mediated microvascular inflammation during sepsis

The University of Sheffield
Faculty of Medicine, Dentistry & Health
Department of Cardiovascular Science
Determining the biological and prognostic significance in pulmonary arterial
hypertension of identified SNPs in osteoprotegerin.
Supervisor: Dr Allan Lawrie & Dr Martina Daly
Project:
Pulmonary Arterial Hypertension (PAH) is a rare disease defined by cardiac catheterisation as a mean pulmonary artery
pressure of at least 25 mmHg. Patients with PAH have significant morbidity and, if untreated, a median survival of 2.8 years.
Pathologically, PAH is characterised by progressive narrowing of small resistance pulmonary arteries and arterioles due to a
process of vascular cell proliferation and inflammatory cell infiltration. We have previously identified that the protein
osteoprotegerin (OPG) in upregulated in pulmonary vascular lesions and serum from patients with PAH. We have recently
demonstrated that OPG is required for the development of PAH in experimental models, and furthermore, that treatment with an
anti-OPG antibody reverses disease in these models. Preliminary data has identified 3 rare haplotypes of the gene encoding OPG
in patient samples obtained from the Sheffield Pulmonary Hypertension Biobank and shown that the rare allele of a nonsynonymous single nucleotide polymorphism (SNP) in Exon 1 of the gene is more common in Idiopathic PAH, associated with
higher serum levels of OPG and predicts a poor prognosis. The aim of this project is to study the genotype to phenotype
relationship of these SNPs using a combination of site-directed mutagenesis and expression studies.
Entry Requirements:
Candidates must have a first or upper second class honors degree or significant research experience.
Enquiries:
Interested candidates should in the first instance contact Allan Lawrie ([email protected]).
How to apply:
Please complete a University Postgraduate Research Application form and attach at least two references to your application.
To complete the application form please visit: www.shef.ac.uk/postgraduate/research/apply.
Please clearly state the prospective main supervisor in the respective box and select ‘Cardiovascular Science’ as the
department.
'The Medical School has received a Silver Athena SWAN award
for promoting gender equality’
Website: http://www.shef.ac.uk/cardiovascularscience
Closing date: 3rd February 2014