BBSRC MRes/PhD Studentship: Nutrient modulation of gut inflammatory responses to microbial challenges, Newcastle University

• Doctoral Training Partnership (DTP)
• Reference Code: CB070

Name of the supervisors
Prof J Hesketh

Dr J Hall

Sponsor
This studentship is sponsored by BBSRC as part of the Doctoral Training Partnership (DTP).

Duration of the award
4 years (MRes Medical and Molecular Biosciences followed by a three year PhD)

Project description
Chronic disorders of the gastrointestinal tract such as inflammatory bowel disorders and colorectal cancer are associated with a dysregulated inflammatory response to microbes. Diet has an important role in maintaining health and inflammatory homeostasis in the gut; however the precise food components involved, their relationships with the gut microbiome and the immune signalling pathways associated with inflammation are not known. This project will investigate how micronutrients and phytochemicals, which are often reduced in diets, influence cell inflammatory mechanisms, particularly the responses of the gut colonic epithelial cells to microbial challenges.
Key components of the innate responses of the host gut epithelium include the TLRs that that sense inflammatory inducers ie microbes, and activate through the unfolded protein response, as well as the NF-κB and Nrf-2 signalling pathways, distinct inflammatory pathways that release effector elements; these effectors include the inflammatory cytokines TNF and interleukins, and the  defensins. Our hypothesis is that a combination of the micronutrient selenium and phytochemicals such as quercetins influence the response of colonic epithelial cells to microbial challenges by modulating inflammatory signalling pathways through effects on the inter-linked pathways that include miRNA, unfolded protein response, Nrf2 and NF-κB signalling pathways.
The student will test this hypothesis in the Caco-2 cell model by using functional genomic approaches to identify the signalling pathways affected by nutrients after an in vitro microbial challenge, and then investigate the changes using realtime PCR, western blotting and reporter gene assays.  The student will receive training in cell culture and general molecular techniques, RNA expression analysis as well as analysis of gut cell-microbe co-culture.

Value of the Award and Eligibility
Depending on how you meet the BBSRC’s eligibility criteria, you may be entitled to a full or a partial award. A full award covers tuition fees at the UK/EU rate and an annual stipend of £13,590 (2011/12).  A partial award covers fees at the UK/EU rate only.

Person Specification
Candidates should have or expect to achieve a 1st class or 2:1 Honours degree in a relevant biological science subject.  

How to Apply
You must complete the University's postgraduate application form. Select "Master of Research/Doctor of Philosophy (Medical Sciences) – Cell and Molecular Biosciences” as the programme of study. Only mandatory fields need to be completed (no personal statement required) but you must attach a copy of your CV and a covering letter, quoting the title of the studentship and reference number CB070.

Closing date for applications 
Prompt application is advised as this post is only available until a suitable candidate is appointed

Further Information
For further details, please contact:
Prof J Hesketh, j.e.hesketh@ncl.ac.uk, +44 (0) 191 222 8744