Evaluating the mucus barrier of wild mice

There is enormous variation in the way individuals respond to infectious disease. Inside the laboratory, conditions are carefully controlled to minimise variation, but in the wild multiple forces combine to determine how a host responds to infection. The proposal takes advantage of our highly tractable wild mouse population on the Isle of May, which allows us to define how intrinsic and extrinsic factors combine to shape the ultimate immune response. The project will explore one particular aspect of the immune response, the mucus barrier in the gastrointestinal tract. Mucus and mucins have been carefully characterised in laboratory mice but whether the findings are recapitulated in wild mouse populations is unknown. Importantly, given that the maintenance of gut integrity is essential for well-being, how investment in an efficient mucus barrier plays out in complex natural surroundings, where co-infections are the norm and the many sources of variation that are removed in the lab have free play is unknown. The project will combine immunology, ecology and biochemistry, biomolecular and computational analyses to address this question and will include field-work on the Isle of May. The project aligns with the BBSRC remit "Bioscience for health" within the theme "World Class Underpinning Biosciences" as it will employ cutting edge approaches to gain a mechanistic understanding of how the mucosal surfaces of the body are maintained under environmental and infectious challenge throughout the lifespan.

The project will enable the student to "exploit new ways of working" by gaining a multidisciplinary training (biochemical, biophysical, immunological and computational approaches) and learn a broad range of skills. The project will integrate modern tools for proteomic and biomolecular characterisation of a complex biological system (mucus). Fieldwork with wild mice will develop the student's in vivo skills. The training environment will provide skills critical for underpinning modern World Class Bioscience research. The cutting-edge approaches available in our labs and the world-class core facilities in FBMH will facilitate cross-discipline bioscience research to investigate a complex biological problem (innate defence by mucus gels). In addition data analysis will include a machine learning approach using a Random Forest machine learning strategy to build predictors of the immune phenotype of interest (e.g. mucus barrier integrity) as a function of genetics and environment. This will be facilitated through a long-standing collaboration with the Data Science and Bioinformatics group at the University of Manchester.