This project will establish a multidisciplinary collaboration between the Quadram Institute, University of East Anglia and the Centre for Mathematical Biology at the University of Oxford thus bringing together international leading scientists with complementary expertise in mathematical and computational biology and in the biology of the gastrointestinal tract.
Dr. Carmen Pin has a strong multidisciplinary background related to her understanding of the biology of the GI tract, mathematical modelling and computing skills. With two degrees, in Veterinary medicine and in Mathematical statistics, and a PhD in Veterinary science, she was recruited to the Institute of Food Research (IFR) in 2002 to enhance its interdisciplinary research.
She initially worked in the field of mathematical modelling in food microbiology and in molecular microbiology, achieving recognized international status as evidenced by invitations to join professional bodies, scientific committees and editorial boards.
She successfully led several industrial projects and Work packages and Tasks in consortiums funded by the EC FP6 and FP7.
In 2010, she joined the integrative biology of the GI tract programme and her science evolved towards modelling cell dynamics in the intestinal epithelium and bacterial interactions in the gut environment. She has explored the possibilities of intestinal in vitro culturing systems and developed an individual based model (IBM) that describes the spatio-temporal cell dynamics in the small intestinal crypt. Simulations of the model generated several testable hypotheses relating to Notch signalling in stem cells and their descendants, and also the passive location of Paneth cells in the crypt base [Pin, Watson and Carding 2012, PLoS ONE 7:e37115].
Prof Simon Carding was recruited to the University of East Anglia (UEA) and the Institute of Food Research (IFR) in 2008 to strengthen the Institute’s efforts in the area of GI tract biology and mucosal immunology. With the support of core funding from the BBSRC-institute strategic programme grant, he leads a programme of research on the Integrated Biology of the GI Tract and he is Professor of Mucosal Immunology at UEA.
He has more than 15 years experience of studying mucosal immunity and the molecular basis of epithelial-immune cell-microbe interactions in gut health and disease research. His research has been supported by programme and charity research grants with a total value that exceeds £6 million. Of direct relevance to this proposal is his experience on using mouse models to investigate different aspects of the intestinal epithelium such as the role of immune cells in maintaining the epithelial barrier function.
Dr Laura Vaux is a cell biologist with an interest in gut biology, with research interests in the molecular mechanisms and signalling pathways that regulate the intestinal stem cell population. She is also interested in how cell-cell interactions drive the proliferation and migration of the intestinal epithelium along the crypt villus axis. Her work involves the use of multicolour lineage tracing of intestinal stem cells under homeostatic and inflammatory conditions both in vitro and in vivo with the use of intestinal organoid cultures.
Laura was previously based at the University of East Anglia, obtaining a PhD from Norwich Medical School where she studied autophagy and innate immunity.
Prof Alastair Watson was appointed Professor of Medicine at the University of Liverpool in 1998 where he served as Head of the Division of Gastroenterology and Head of the Department of Medicine. In 2010 he was appointed to the University of East Anglia as its first Professor of Translational Medicine.
The quality of his science has been recognized by a number of prestigious national and international awards. Of particular relevance to this project is his work on the regulation of cell death in intestinal epithelial cells. By developing an in vivo microscopy method for the observation of epithelial cell shedding in mice, his team has revealed the mechanisms that ensure the maintenance of the epithelial barrier during cell shedding. [Kiesslich et al. and Watson 2007, Gastroenterology 133, 1769-78; Marchiando et al. and Watson 2011, Gastroenterology 140, 1208-1218; Guan, Watson et al. 2011, Am J Physiol-Cell Ph 300, C1404-14].
Centre for Mathematical Biology
Prof Philip Maini, appointed Professor of Mathematical Biology and Director of the Centre for Mathematical Biology at Oxford in 1998, has 25 years’ experience in developing mathematical and computational models in a number of areas in the life sciences.
His high impact research is extensively published. He has been awarded a large number of prizes and distinctions in recognition of his work. His research has been funded by the UK-RCs and a number of national and international bodies.
He is a co-founder of the partnership between the King Abdullah University of Science and Technology and the Oxford Centre for Collaborative Applied Mathematics (2008-13) with initial funding of 25 million dollars. Important to this project, is his extensive modelling work in the intestinal crypt which has been carried out by using and simultaneously developing Chaste, ‘Cancer, heart and soft-tissue environment’, a software library for simulating complex multiphysics and multiscale biological systems [Pitt-Francis et al. Maini, Byrne and Gavaghan 2009, Comp Phys Commun 180, 2452-71]. The initial focus of the cancer branch of Chaste was the implementation of a detailed multiscale model of the colonic crypt, linking sub-cellular, cellular and macroscale components, leading to new insights into clonal expansion and cellular fate, mediated by Wnt signalling [van Leeuwen et al. Maini and Byrne 2009, Cell Prolif 42, 617-36]. Chaste has also been applied to investigate the relationship between discrete models of individual cell behaviour and continuum models at the population level [Murray et al. and Maini 2009, Phys Rev E 80], to explore scenarios in which a mutant cell population can colonize neighbouring healthy crypts [Murray et al. Byrne, Maini and Cho 2010, Biophys J 99, 716–25] and the top-down and bottom-up invasion of the crypt by cancerous cells [Osborne et al. et al. Maini, and Byrne 2010, Phil Trans R Soc A 368, 5013-28; Mirams, Maini, and Byrne. 2012, J Theor Biol 312, 143-156].
Prof Helen Byrne is an applied mathematician whose research focuses on the development and analysis of mathematical models of biomedical systems. She was awarded a prestigious advanced fellowship by the EPSRC in 1998 and promoted to Professor of Applied Mathematics in 2003.
Prof Byrne recently moved to the Oxford Centre for Collaborative Applied Mathematics. As founding Director of Nottingham’s Centre for Mathematical Biology and as co-organizer of Mathematics-in-Medicine study groups, she has played a key role in promoting the application of mathematics to medicine and biology.
She is currently a member of the BBSRC’s Integrative and Systems Biology Strategy Panel and editor of a number of theoretical journals. She brings complementary expertise in modelling intestinal stem cells, wound healing, and the growth of solid tumours in three dimensions and an extensive research track record of successful collaboration in modelling the intestinal epithelium.
Dr Alexander Fletcher is an applied mathematician whose research interests include the mechanisms and interactions underlying intestinal homeostasis and carcinogenesis, as well as stem cell population dynamics more generally. He is also interested in how various cell-level processes contribute to the dynamics of epithelial cell sheets during development.
He uses a variety of modelling approaches to address questions in this area, from compartment models to individual cell-based and multiscale models. To support this work, he plays a key role in the ongoing development of an open source simulation environment, Chaste (http://www.cs.ox.ac.uk/chaste).
Dr Fletcher has held a Research Fellowship in Computational Science associated with the 2020 Science project (http://www.2020science.net) since July 2011. Prior to this he was funded by the Oxford Centre for Integrative Systems Biology (http://www.sysbio.ox.ac.uk/) as a postdoctoral researcher studying mathematical approaches to systems biology research. He is based at the Wolfson Centre for Mathematical Biology at the University of Oxford.
More details can be found at his personal webpages (http://people.maths.ox.ac.uk/fletcher).