Prof. Alastair Watson
WebsiteIFR Gut Health and Food Safety Programme
I have a long-standing interest in the regulation of cell death in intestinal epithelial cells. Recently I have become interested intestinal epithelial cell shedding, a special form of cell death which arises as a consequence of the high flux of epithelial cell which arise from stem cells at the base of crypts and migrate up to the villi in the case of the small intestine or intestinal surface in the case of the colon.
When a cell is shed a discontinuity is created in the epithelial monolayer that has been named a “gap”. Under normal conditions the “gap” is short lived and barrier function is maintained at sites of cell shedding. However, during inflammation cell shedding is increased and can become confluent leading to the formation of micro-ulcers. Barrier function is also sometimes lost during inflammation, creating sites for the potential entry of microorganisms and luminal antigens.
Recent projects within the Gut Health programme at IFR focus on the regulation of cell shedding by the gut microflora. This has wide ranging applications to gut inflammation and inflammatory bowel disease.
We are also particularly interested in how cell shedding from the villus tip is coordinated with cell division and the base of the crypt. We are taking a systems biology approach to this combining mathematical modeling with colleagues in Oxford with experimental observations.
Scientists and clinicians on the Norwich Research Park have carried out the first detailed study of how our intestinal tract changes as we age, and how this determines our overall healthmore +
The University of East Anglia & IFR are keen to host Marie Skłodowska-Curie Fellows and are encouraging applications to the scheme, particularly within the following areas of research:Gastroenterology science, mucosal immunology and epithelial biology, Nutrition and Health, Microbiology and antibiotic developmentmore +
R. Kiesslich, CA Duckworth, D Moussata, A Gloeckner, LG Lim, M Goetz, DM Pritchard, PR Galle, MF Neurath, AJM Watson. Local Barrier Dysfunction Identified By Confocal Laser Endomicroscopy Predicts Relapse In Inflammatory Bowel Disease. Gut 2012;61 1146-1153.
Anne V McNamara, Monica Barclay, Alastair J Watson, John R Jenkins. Hsp90 inhibitors sensitise human colon cancer cells to topoisomerase I poisons by depletion of key anti-apoptotic and cell cycle checkpoint proteins. Biochemical Pharmacology 2012;83(3):355-67.
Pin C, Watson AJM, Carding SR. Modelling the spatio-temporal cell dynamics reveals novel insights on cell differentiation and proliferation in the small intestinal crypt PLoS ONE 2012 7(5):e37115.
Becker C, Watson AJ and Neurath MF.. The Intricate Role of Caspases in the Pathogenesis of Inflammatory Bowel Disease. Gastroenterology 2013;144:283-293.
Méniel V, Song F, Phesse T, Young M, Poetz M, Parry L, Jenkins JR,Williams G, Dunwoodie SL, Watson AJM, Clarke AR. Cited1 deficiency suppresses intestinal tumorigenesis. PLOS Genetics 2013;9:e1003638.
Williams JM, Duckworth CA, Watson AJM, Frey MR, Miguel JC, Burkitt MD, Sutton R, Hughes KR, Hall LJ, Caamaño J, Campbell BJ, and Pritchard DM. A Mouse Model of Pathological Small Intestinal Epithelial Cell Apoptosis and Shedding Induced by Systemic Administration of Lipopolysaccharide. Disease Models & Mechanisms. 2013 Nov;6(6):1388-99. doi: 10.1242/dmm.013284.
Hammoudi A, Song F, Reed KR, Jenkins RE, Meniel VS, Watson AJM, Pritchard, DM, Clarke AR. Jenkins JR. Proteomic profiling of a mouse model of acute intestinal apc deletion leads to identification of potential novel biomarkers of human colorectal cancer (CRC). Biochemical and Biophysical Research Communications. 2013;440(3):364-70.
Parsons BN, Paul Wigley P, Simpson HL, Williams JM, Humphrey S, Salisbury AM, Watson AJM, Fry SC, O’Brien D, Roberts CL, O’Kennedy N, Keita A, Söderholm JD, Rhodes JM and Campbell BJ. Dietary supplementation with soluble plantain non-starch polysaccharides inhibits intestinal invasion of Salmonella Typhimurium in the chicken. PLOS ONE 2014 (In Press).
Lee Guan Lim, Neumann J, Hansen T, Goetz M, Hoffman A, Neurath MF, Galle PR, Chan YH, Kiesslich R, Watson AJM. Confocal endomicroscopy identifies loss of local barrier function in the duodenum of patients with Crohn’s disease and ulcerative colitis. Inflammatory Bowel Diseases 2014 (In press).
Günther C, Buchen B, Gui-Wei He G-W, Hornef M, Torow N, Neumann H, Wittkopf N, Martini E, Basic M, Bleich A, Watson AJM, Neurath MF and Becker B. Caspase-8 controls the gut response to microbial challenges by Tnf-α-dependent and –independent pathways. GUT 2014 (In press)
Anja Sandek, Alexander Swidsinski, Wieland Schroedl, MD, Alastair Watson, MD, Miroslava Valentova, Ralph Herrmann, Nadja Scherbakov, Larissa Cramer, Mathias Rauchhaus, Anke Grosse-Herrenthey, Monika Krueger, Stephan von Haehling, Wolfram Doehner, Stefan D Anker, Juergen Bauditz. Intestinal blood flow in patients with chronic heart failure – a link with bacterial growth, gastrointestinal symptoms and cachexia. Journal of the American College of Cardiology. 2014 (In press).
- Kevin Hughes
- Cristina Alcon
- Chris Wright