Identifying a novel diagnostic test to predict clinical response to treatment with biological drugs in Crohn’s disease patients

Background:

Crohn’s disease (CD) is a chronic relapsing incurable inflammatory bowel disease (IBD) affecting approximately 165/100000 people in the UK. The cytokine milieu in the intestine is an important factor in the maintenance of the immune balance, and in gut inflammation, this balance is dysregulated resulting in mucosal inflammation. The gastrointestinal tract interacts with a huge variety of diverse microbiota. Changes in the diversity of this microbiota (dysbiosis) is associated with changes in the cytokine profile and considered to be an important factor in the aetiology of CD.

Monoclonal antibody therapy has revolutionised the treatment of IBD. However, many patients do not respond to the drugs and some develop serious side effects and/or recurrence after the treatment is discontinued. Furthermore, information on the effect of biological drugs on the bacterial composition in relation to the systemic cytokine profile in CD is still unknown.

Hypothesis:

Dysbiosis in CD correlates with systemic changes in the production of pro- and anti-inflammatory cytokine.

Aims:

To characterise dysbiosis in CD and examine concurrent changes in gut bacteria and serum cytokine profiles in response to treatment with biological drugs including vedolizumab and infliximab.

Research Plan:

Pro- and anti-inflammatory cytokines, immune cell phenotype and activation will be assessed by flow cytometry on serum and blood immune cell samples obtained from CD patients. Bacterial DNA will be extracted from stool samples and dysbiosis of gut microbiota will be assessed before and after biological treatment using Luminex technology and GA-map Dysbiosis Test. 

Advanced statistics and bioinformatics will be used to determine the relation between the cytokine levels and dysbiosis.

Outcome:

The data obtained will potentially help predict patient response to biological drugs and will bring closer the notion of personalised medicine.

For further information regarding the project or an informal discussion please contact Director of Studies, Dr Hafid Omar [Email Address Removed]

Applications

To apply for the PhD Research Studentship applicants must hold a first class/distinction at Master and/or Bachelor level of study.

Applications to include one identified project, a full CV (including 2 referee names and contact details), transcripts and a letter of application outlining the motivation for applying (maximum of 2 pages). Applicants from outside UK must provide evidence of English Language requirement as stated in https://www.wlv.ac.uk/research/research-degrees/

Application submission deadline is 10:00am BST 19 June 2023 to [Email Address Removed]

A shortlist of candidates will be prepared from the pool of applicants, in line with Faculty of Science and Engineering Post Graduate Research (PGR) studentship selection criteria, who will be invited to attend an interview with a panel of academic staff, week commencing 26 June 2023.

Following this process all successful candidates will be notified to enrol in July 2023 on a PhD degree programme. The studentship award will include tuition fees at home level for the first three years of full-time study including any write-up period fees and research support fees.

For further information on fees https://www.wlv.ac.uk/apply/funding-costs-fees-and-support/fees-and-costs/research-fees/

Informal enquiries are welcome and should be directed to individual Director of Studies mentioned above.