This branch of gastrointestinal (GI) research is based on the main University Campus (Stopford Building) to foster close links and collaborations with other biomedical researchers in the other faculty institutes and the Faculty of Life Sciences. The state-of-the-art core facilities now established on campus enable us to undertake cutting-edge interdisciplinary basic research, complementary to the experimental physiology and medicine undertaken on the hospital sites.
Our key areas of focus include:
- Enteroendocrine cell physiology
- Nutrient sensing
- Mucosal immunology
- Cell and molecular biology in the epithelial barrier
Local regulation of GI function
The day-to-day functioning of the gut is very much orchestrated by enteroendocrine-enteric nervous system interactions and dysfunction within this organisation can arise from, i.e. inflammation and/or changes in gut microflora.
We are currently exploring the role of the microflora in gut dysfunction and the expression of symptoms, such as abdominal pain and bloating, and how modulation of the microflora with agents such as probiotics can ameliorate such symptoms in patients with functional GI disorders. Evaluation of enteroendocrine cell release of amines such as serotonin and how this relates to symptomatology and pathophysiology is also been examined.
All research programmes are carried out in both healthy volunteers and patients with functional GI disorders, and are enhanced by our concomitant research programme to better delineate the true meaning of abdominal symptoms to patients. For example we have shown that the symptom of bloating, often described by functional GI patients as their most frequent and bothersome, is not always associated with a physical increase in abdominal girth (i.e. distension) and that the mechanisms responsible for the sensation of bloating and objective distension may differ, and possibly between patient groups.
The gastrointestinal response to food
The gut is the first point of contact for ingested nutrients, and their presence in the gut lumen is sensed by the gut, evoking signals that control the physiological response to food and the short-term regulation of food intake. These processes are largely mediated by the enteroendocrine-vagus nerve axis.
We are actively exploring these mechanisms in health and disease, with a key focus on the regulation of gastric function, the biological basis for sensations and symptoms arising from the gut, and the central neural correlates of gastrointestinal nutrient sensing.
These studies are conducted in healthy volunteers and patient groups. We are particularly interested in developing non-invasive techniques for the investigation of gut physiology (such breath testing by stable isotope spectrophotometry, and functional magnetic resonance imaging). This work is also enhanced by applying a genomics-based approach to physiological variability, and fully integrated with the research mission of the epithelial biology group.
Motor-sensory and psychological disturbances are often associated with functional GI disorders. Why some, but not all, patients exhibit these phenomena is unknown but evidence is emerging of a possible genetic link to these phenotypic variations. We are currently engaged in a successful collaboration with the Department of Human Molecular Genetics at the University of Heidelberg to investigate whether cis-regulatory variants in the untranslated regions of the genes of various receptors, such as the 5-HT3 receptor may be predisposing or contributing to the symptomatic and physiological phenotypes seen in various groups of patients with functional GI disorders.
Our programme of research is coordinated around understanding the molecular basis of the gastrointestinal response to food and nutrient molecules. We are addressing this in the following key domains:
- Molecular mechanisms of nutrient sensing in the GI tract
- The cellular and molecular biology of enteroendocrine cells
- Epithelial biology
- Tight junctions and regulation of the epithelial barrier
- Cellular biochemistry of the gut epithelium
- Impact of dietary components on these structures
- Mucosal immunology
- Effects of inflammation of enteroendocrine cells and food intake
- Genetic basis of epithelial pathophysiology
This work has largely been laboratory focused, but translational and patient-oriented projects are now underway, flowing from this bench research work into the clinical arena. We are closely collaborating with groups both in Manchester (Faculty of Life Sciences: Physiology and Immunology), as well as investigators in London (Bart’s and the London) and Keele University. We also have a strategic partnership with the Gastrointestinal Diseases Research Programme at McMaster University, Hamilton, ON, Canada.
We employ a wide range of laboratory and investigative approaches to answer our research questions (cellular and molecular biology, imaging, in vivo models, systems biology) and benefit from direct access to the state-of-the-art biomedical research facilities on the University of Manchester Campus.
The University of Manchester is not responsible for the content of external internet sites.