Effect of Hypoxia (Low Oxygen) on Macrophage Gene Expression - Development of New Hypoxia Targeted Gene Therapy Strategies

Macrophages are white blood cells (leukocytes) which accumulate in hypoxic diseased sites such as cancer, atherosclerotic plaques, arthritic joints, infarcted heart tissue after heart attacks, and also in Tuberculosis granulomas. Recently it has been discovered that the hypoxia (low oxygen levels) present at such sites plays a vital role in these diseases.

Hypoxia and ischaemia (poor blood flow) alter the phenotype of macrophages in a way that can promote development of disease, for example by causing the macrophage to secrete pro-inflammatory and pro-angiogenic (blood vessel growth stimulating) proteins. However the range of genes upregulated and functions carried out by macrophages in such hypoxic tissues are not fully understood.

A greater understanding of the role macrophages play in disease processes will enable the development of strategies to block their ability to carry out pro-disease functions, in order to slow disease progression. An additional, alternative strategy has also been proposed: to make use of the tendency of macrophages to accumulate in diseased sites to use them as delivery systems to carry therapeutic molecules, such as gene therapy DNA constructs, into these sites.

This project will use the latest Molecular Biology techniques to investigate the responses of human macrophages to hypoxia, including such techniques as Real-Time RT PCR, Promoter / reporter gene analysis, and Western Blotting. The information obtained from these initial experiments will then be used to design, implement and test novel gene therapy strategies with a view to designing a Gene Therapy procedure to improve the outcome of diseases associated with hypoxia and macrophage accumulation.

This project would suit someone with an enquiring mind who wants to contribute to improvements in human health. Some knowledge of Molecular Biology and Cell Culture would be an advantage, although full training will be provided, both by the supervisor and the Department.

Department Information
The Centre of Applied Biological & Exercise Sciences furthers the understanding of fundamental biological pathways and processes; applying biological sciences to advance diagnosis and prevention of disease. This project will support theme 1 within the ABES centre, which focusses on cellular & molecular systems.

Candidate Specification
• A minimum of a 2:1 first degree in a relevant discipline/subject area (e.g. chemistry, biochemistry, electrochemistry) with a minimum 60% mark in the Project element or equivalent with a minimum 60% overall module average.
• or in the event of a first degree classification of less than 2:1, a Masters Degree in a relevant subject area (see above) will be considered as an equivalent. The Masters must have been attained with overall marks at merit level (60%). In addition, the dissertation or equivalent element in the Masters must also have been attained with a mark at merit level (60%).
• the potential to engage in innovative research and to complete the PhD within a three-year period of study.
• a minimum of English language proficiency (IELTS overall minimum score of 7.0 with a minimum of 6.5 in each component).
The most recent and highest award will be used for assessment in all cases

Additional:
• Knowledge of molecular biology and cell culture

How to Apply
Application form and full supporting documentation (as per the checklist) plus covering letter only

Eligibility
UK/EU/International students may apply with the academic requirements as listed on: http://www.coventry.ac.uk/research/research-students/research-entry-criteria/

Start date: September 2017 (ideally, but rolling otherwise)

Duration of study: Full-Time – three years fixed term

Application deadline: Ongoing- please be aware that this opportunity will only remain open until such time as a suitable candidate is identified therefore early application is highly recommended for this opportunity

Enquiries
Before completing the application documentation please contact the lead academic for an initial informal discussion about this opportunity: Dr Bernard Burke ([Email Address Removed])