Rheumatoid arthritis is an autoimmune condition in which inflammation of synovial joints can lead to progressive destruction of joints and eventual disability if the inflammation is not controlled. Fortunately, there are a variety of treatment options that work by blocking inflammatory pathways, one of the most important of which is the IL6 pathway. Tocilizumab and Sarilumab are biologic drugs that block IL6, but not all patients treated with these medications will respond well to them. The aim of the project is to identify genetic, transcriptomic and cytokine signatures that predict which patients will not respond, as a first step to a precision medicine approach to targeting treatments to the patients most likely to respond.
We have collected blood samples from patients (n = 200) before they start IL6-inhibitor therapy and have followed them up over 12 months to identify those in whom the treatments are effective/ineffective. The project will involve analysing the pre-treatment samples and using statistical analysis to identify pre-treatment biomarkers of response/non-response.
Year 1: Current review of the literature relating to biomarkers of response to IL6 inhibitors; collate information on available samples and genotyping, genotype samples where data is not already available
Year 2: Generate cDNA from available samples, RNA-seq data generation and analysis
Year 3: Measure drug levels and undertake combined multi-omic analysis to identify biomarkers of therapy response. Write thesis.
Eligibility
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline. Candidates with experience in statistical analysis, bioinformatics or biomedical science are encouraged to apply.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/