Anticipated start date for project: September 2013 or January 2014
Closing date for applications: 15 July 2013Â
It has yet to be shown whether macrophages and dendritic cells (DCs) divide in the lung during pulmonary inflammation, and what the implications of this might be on disease progression or resolution. The level of involvement of key transcription factors or epigenetic regulators in these processes is also currently unknown.
The project will use well-established murine models of pulmonary inflammation to characterize the proliferation and activation of recruited vs. tissue resident macrophages and DCs ex vivo. Our initial focus will be on the respiratory allergen House Dust Mite (HDM) and, as a more reductionist and complementary approach, administration of the canonical Type 2 cytokine IL-4. Isolated macrophages and DCs will also be characterized by microarray or deep sequencing (mRNA and miRNA). Once established, proliferation and inflammation in WT animals will be compared to available genetically modified mice that are deficient in key transcription factors or proteins implicated in epigenetic regulation of innate cell activation and function.
To directly assess the relevance of the results generated using these murine experiments to the âreal worldâ situation, we will take advantage of published and in-house mRNA and miRNA profiling datasets from macrophages and DCs purified from stratified patient cohorts, in collaboration with Prof. Tracy Hussell. This will allow us to determine expression patterns of transcription factors and epigenetic regulators in human disease, which we can then relate back to our murine data.
These innovative experiments will allow us to determine whether or not macrophages and DCs proliferate during murine and human pulmonary Type 2 inflammation. In addition, they will reveal exciting new information about how key transcription factors and epigenetic mechanisms regulate these processes. This will inform rational design of therapeutics aiming to modulate pulmonary inflammation.
Qualifications applicants should have/expected to receive: Applicants should hold a minimum upper-second honours degree (or equivalent) in a biological/medical science, biochemistry, pharmacology or related area. A related Masters qualification or extensive research experience (> 2 years) would be an advantage.
Amount of funding available and eligibility: Each award provides an annual tax-free stipend of, Â£19,000 and covers tuition fees and research expenses. Whilst funding is limited to UK/EU tuition fee rates, MCCIR will consider applications from outstanding non-EU nationals if they can cover the difference in UK/EU and international fees.
How to apply: Please email Expression of Interest to [email protected]Â via theÂ Apply button below.
- Statement of support (outlining the applicantâs suitability for the research proposal, what the applicant hopes to achieve from the PhD and research experience to date)
- Contact details for two referees
- Academic transcripts