Anticipated start date for project: September 2013 or January 2014
Closing date for applications: 15 July 2013Â
The interplay between immune cells during respiratory inflammation has been studied at length using animal models. However, the translation of these findings to human, particularly in the context of Type 2 inflammation and respiratory diseases such as asthma, has been limited due to inability to perform similar studies in complex human multi-cellular systems. Airway epithelial cells are the first line of defence against inhaled material such as allergens. Further, interactions between epithelial cells (ECs) and dendritic cells (DCs) play a central role in shaping the local airway mucosal and systemic immune response. The aim of this project will be to establish a human bronchial co-culture model to study the outcome of crosstalk between ECs and DCs on their activation and function in response to inflammatory challenge. A better understanding of the mechanistic detail of pulmonary EC/DC interactions will ultimately lead to new and better treatments for respiratory inflammation.
We will use the 3 dimensional human air-liquid interface (ALI) bronchial EC system, supplemented with human monocyte derived DCs to develop a multi-cellular in vitro platform that shares some components of the human lung. We will expose this system to stimulation and characterize EC and DC activation phenotype by flow cytometry and qPCR. This readout will include key markers of activation and regulation, as well as profiling for molecules associated with epigenetic control. Once this system has been established, a more detailed characterization of EC and DC activation will be carried out by microarray or deep sequencing for mRNA and ÂµRNA changes post-challenge. Our initial focus will be respiratory allergens, with the potential to look at additional relevant stimuli.
This innovative project will develop a novel human multi-cellular platform that mimics the lung cellular environment to enable definition of the molecular consequences of crosstalk between epithelial cells and dendritic cells following exposure to respiratory stimuli.
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] via the ‘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