Kennedy Trust Prize Studentships
The interaction between the gut microbiome and host genetics across different diseases of the immune system
Host genetics, the resident microbes of the gut and the interaction between the two may be critically involved in the development of a diverse set of chronic inflammatory diseases including arthritis and inflammatory bowel disease. However, while genome-wide association studies have shown that many of the same risk genes are active across these diseases, how these genes impact the patient's immune system, and how they interact with the bacteria the patient carries, is still largely a mystery.
To address the links between host genetics and the gut microbiome in the aetiology of chronic inflammatory disease, researchers at the Kennedy Institute work with both the Inflammatory Arthritis Microbiome Consortium (IAMC) and the UK Inflammatory Bowel Disease Genetics Consortium who are collecting multiple genome- and metagenome-scale datasets in patient cohorts representing rheumatoid arthritis, ankylosing spondylitis, Crohn's disease and ulcerative colitis.
This project will analyse data across these different diseases in order to study how genetic and microbiome risk is shared between inflammatory disorders, and what makes each of these diseases unique. The student will work closely with experts in computational genomics and metagenomics to develop new statistical techniques for analyzing high dimensional data across multiple diseases simultaneously. They will develop new methods of catagorising the function of genetic and microbiome risk pathways, and studying how they interact with each other. These analyses will drive the development of novel hypotheses regarding the functional impact of specific genes and microbes on host immunity that will be experimentally tested in model organisms and patient cells.
This PhD would give the student a unique opportunity to work closely with both computational and experimental groups. The Kennedy Institute has cutting edge microbiological and computational facilities, and this project would suit a student who has excellent data analysis skills combined with a drive to answer real biological questions.
The Kennedy Institute is a world-renowned research centre and is housed in a brand new state-of-the-art research facility. Training will be provided across the range of cell and molecular, computational genomics and statistical genetics techniques. A core curriculum of 20 lectures will be taken in the first term of year 1 to provide a solid foundation in musculoskeletal sciences, immunology and data analysis. Students will attend weekly departmental meetings and will be expected to attend seminars within the department and those relevant in the wider University. Subject-specific training will be received through our group's weekly supervision meetings. Students will also attend external scientific conferences where they will be expected to present the research findings.
- Ilott NE, Bollrath J, Danne C, Schiering C, Shale M, Adelmann K, Krausgruber T, Heger A, Sims D and Powrie F (2016). Defining the microbial transcriptional response to colitis through integrated host and microbiome profiling. ISME J. doi: 10.1038/ismej.2016.40. [Epub ahead of print]
- Brown MA, Kenna T and Wordsworth (2016). Genetics of ankylosing spondylitis—insights into pathogenesis. Nature Reviews Rheumatology 12, 81–91
- Jostins L, Ripke S et al (2012). Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. 491(7422):119-124 Nature
Statistical genetics; Mucosal immunology.
Dr Luke Jostins, University of Oxford
Professor Fiona Powrie, Kennedy Institute, University of Oxford