This project is one of a number that are in competition for funding from the ‘GW4 BioMed MRC Doctoral Training Partnership’ which is offering up to 18 studentships for entry in September 2020.
The DTP brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities.
Lead supervisor: Prof Steven Bull, Department of Chemistry, University of Bath
Co-supervisors: Dr Vicky Hunt (Bath) and Dr Laura Peachey (Bristol)
Parasite infection in the gastrointestinal tract are associated with an oxidative stress response that releases reactive oxygen species (ROS) and reactive nitrogen species (NOS) as components of the host immune response to infection. However, this oxidative response is known to damage both the host tissue and the parasite, as well as causing changes in the gut microbiota in a bi-directional manner.
Understanding the type of free radicals produced in these oxidative stress responses and their role in host-parasite interactions could lead to the development of improved treatments for controlling parasites and the diseases they cause. Furthermore, common gut diseases such as inflammatory bowel disease, Crohn’s disease and ulcerative colitis are all associated with intestinal changes to oxidative stress. If we can understand how both the host and parasite mitigate (or avoid) damage caused by oxidative stress, then we can potentially develop treatments for these gut diseases.
We know surprisingly little about the oxidative stress that occurs in the intestine during parasitic infection, which is due to limitations in the techniques currently used to determine levels of oxidative stress and identify free radicals. We have recently developed novel fluorescence probes to accurately measure and visualise different types of ROS and NOS, and we intend to use these probes to investigate oxidative stress responses during parasite infection in the small intestine.
We intend to address the following questions:
i) Which ROS and NOS are produced during infection and how are they distributed throughout the gut?
ii) How do ROS and NOS levels change as infection progresses?
iii) What strategies have the parasite/host evolved to deal with increased ROS and NOS levels? For example, do they secrete antioxidants?
iv) How does parasite-induced oxidative stress impact the gut microbiota and what strategies have the microbiota evolved to deal with ROS?
To address these questions, we will work with the parasitic nematode Strongyloides, which is a gastrointestinal parasite of the small intestine, applying our newly developed fluorophores to visualise ROS and NOS in the small intestine tissues ex vivo. Host, parasite and microbiota responses during infection will be identified by studying gene expression levels (using RNAseq), proteomics (mass spectrometry) and amplicon sequencing of the microbial 16s rRNA gene. We will also explore oxidative stress response in gut cell lines and investigate if molecules secreted by the parasite can reduce oxidative stress and inflammation of the gut.
The student will receive training in state of art chemical biology techniques, including organic synthesis, fluorescent imaging, molecular biology, genetics, parasitology and microbiology.
The PhD project will be jointly supervised by Professor Steven Bull (Organic Chemistry) and Dr Vicky Hunt (Wellcome Fellow/Lecturer in Biology) at the University of Bath, and Dr Laura Peachey (Lecturer in Veterinary Parasitology) at the University of Bristol. These supervisors have numerous collaborators in leading groups in the US, Japan and China and there will be ample opportunities for the PhD student to visit these laboratories.
Applicants for a studentship 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 an area appropriate to the skills requirements of the project.
IMPORTANT: In order to apply for this project, you should apply using the DTP’s online application form: https://cardiff.onlinesurveys.ac.uk/gw4-biomed-mrc-doctoral-training-partnership-student-appl
You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding form the DTP will be required to submit an application to study at Bath.
More information on the application process may be found here: https://www.gw4biomed.ac.uk/doctoral-students/
APPLICATIONS CLOSE AT 17:00 ON 25 NOVEMBER 2019.