Chemical exposure and susceptibility to systemic sclerosis
Dr Andrew Povey and Dr Ariane Herrick
The aim of this PhD research study is to investigate susceptibility to systemic sclerosis as a result of chemical exposure.
Systemic sclerosis (SSc) is a rare disease long associated with exposure to certain chemicals including silica and certain organic solvents. Not all individuals exposed to these agents develop SSc which suggests some underlying genetic component. The pathways leading to SSc are not fully characterized but may involve autoantigen formation and defective apoptosis.
In a previous study¹, we found that repeated exposure to sonicated silica can induce certain aspects of the SSc phenotype in a fibroblast cell line (namely a reduced fibroblast sensitivity to Fas induced apoptosis) and that differences in silica induced apoptosis and gene expression were observed between fibroblasts obtained from SSc patients and healthy individuals. The proposed study will continue and expand this work so as to determine its wider significance and may lead to the identification of novel biomarkers of SSc susceptibility
The over-riding aims of the research are to:
- Better characterise the cellular changes that occur following exposure to agents associated with SSc;
- Determine differences in how cells obtained from SSc cases and healthy individuals differ in their responsiveness.
This project would be ideally suited to an individual keen to engage in research that spans both laboratory and epidemiological components and is interested in toxicology. The study will be conducted jointly within the Centre for Occupational & Environmental Health and Musculoskeletal Research Group. Interlinked laboratory and epidemiological training will be provided in cell culture techniques, molecular analyses (e.g. real time PCR, Westerns), and toxicity assays (e.g. MTT, apoptosis) and the design, management and analysis of human population studies.
Upon completion, progression into a postdoctoral career within academia or industry would be anticipated.
Applicants should hold, or expect to obtain, a minimum upper-second honours degree (or equivalent) in biochemistry, molecular biology or a related area. An appropriate Masters degree and previous experience of cell culture and molecular biology techniques would be beneficial but are not essential.
This 3-year project is open to UK/EU and non-EU nationals but no funding is provided. Applicants must therefore be able to provide evidence of their ability to provide self-arranged funding. Annual tuition fees for this project are:
*UK/EU nationals: £17,000
Non-EU nationals: £27,300
Please direct applications in the following format to Dr Andy Povey:
- A CV, including full details of all University course grades to date.
- Contact details for two academic or professional 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 Povey.
*UK/EU nationals should note that the tuition fee is subject to an annual increase of approximately 1.5-2.5%.
¹ England H et al. Silica-induced resistance of cultured fibroblasts to fas-induced apoptosis: implications for scleroderma. Rheumatology 2008; 47 (suppl2) #298, ii88