Download From SICSA website - Robert Gordon University

Institute for Health & Welfare Research
MRC CASE 4 Year PhD Studentship
Closing Date: Friday 25th May 2012.
Applications are invited from candidates who are interested in applying for a fully funded
MRC CASE scholarship, supervised by Professor Cherry Wainwright and in collaboration
with Astra Zeneca, Mölndal, Sweden, to study for a PhD in the Institute of Health &
Welfare Research at the Robert Gordon University in Aberdeen, Scotland, UK.
Title of project:
A transgenic approach to the elucidation of the role of the orphan receptor
GPR55 in cardiac remodelling induced by metabolic disease
Project detail:
Elevated blood glucose and high circulating cholesterol cause damage to the heart
resulting in changes in the structure and function of the heart muscle (myocardial
fibrosis), resulting in cardiac failure and increased morbidity. A key event in myocardial
fibrosis is an imbalance between the synthesis and degradation of extracellular matrix
material, in particular collagen. Moreover, the extent of collagen cross-linking
determines the elasticity of the extracellular matrix material and is pivotal to
determining the contractility of the heart. GPR55 is an orphan receptor activated by
endogenous cannabinoid-like ligands. Previous work has demonstrated an influence of
endocannabinoids in cardiac fibrosis, however the receptor(s) mediating this effect are
unknown. This studentship aims to determine the role of GPR55 in hyperglycaemia and
hyperlipidaemia-induced fibrosis using knockout mouse models for these metabolic
disorders with an additional gene deletion for GPR55.
By using a double knockout transgenic approach in mice, the project will explore the role
of the orphan receptor GPR55 in the development of cardiac dysfunction resulting from
hyperlipidaemia and metabolic syndrome. Combined in vivo (non-invasive Doppler
echocardiography and the measurement of pressure volume loops; PVL) and
histopathological studies will be used to determine the functional and structural
characteristics of these diseases in the presence and absence of GPR55. The concurrent
use of primary isolated cardiac fibroblasts from these mice will explore alterations in the
cellular mechanisms involved in fibrosis and will be used to develop a platform for drug
discovery of anti-fibrotic drugs. Finally, complimentary studies using cardiac fibroblasts
from patients with hyperlipidaemia and/or metabolic syndrome will be undertaken to
establish the mouse model as an appropriate model for human disease.
Candidates should be highly motivated with a strong commitment to academic research.
A First Class, or a 2.1 Honours Degree (or equivalent) or a Masters Qualification in a
relevant biomedical science discipline is absolutely essential. Enquiries about the project
can be sent to [email protected].
The studentship provides full university fees for UK/EU applicants, a tax-free
maintenance allowance of £16,090 per annum for 4 years (UK Research Council
Rates plus supplementary CASE allowance) and full running costs. The
successful candidate will be expected to spend some research time in the
laboraotires of the partner company in Molndal, Sweden. The studentship is
available to start in October 2012. Interviews will be held on the 7h / 8th June
2012.
Application process
Applicants should Apply Online at:
http://www.rgu.ac.uk/researchdegrees/applicants/page.cfm?pge=26828, uploading all
required documents, quoting “MRC CASE Award” to identify the project you are
applying for. Once an Apply Online account has been set up, please check the
Yes box to “Are you applying for an advertised studentship?” and then select
MRC CASE Award from the drop down list.