Gut neuroscience research focuses on the neuronal basis of functional bowel diseases and the neurophysiology of the peripheral nervous system in conditions such as obesity, inflammation, and aging.
We focus on the roles of ATP and serotonin (5-HT) in neurotransmission and sensory transduction using electrophysiological and electrochemical techniques.
Our research is aimed at revolutionising the functional diagnoses of gastrointestinal disorders by using state-of-the-art micro-sensor technology. We aim to uncover the neuronal and hormonal control of the gastrointestinal tract to establish a foundation for tailored diagnostics for gastrointestinal disorders.
We look at real-time measures of hormone levels in the gut can with the idea that this could act as a diagnostic tool. Our hypothesis is that neuroendocrine cells in the epithelium of the gut act as sensors that release hormones onto the sensory nerve terminals and immune cells, and thus affect gastrointestinal function. Our area of research is neuroscience across three research themes: serotonin, purines, and sensory transduction. This program was initiated in 1994 and has continued through to the present project grant (NHMRC GNT1048885, 2013-15).
Research interests: Neurophysiology of the enteric nervous system (ENS); control of gastrointestinal (GI) function; neuroplasticity; obesity, inflammation, aging; 5-HT transporter; enterochromaffin cells; TRP and pannexin channels; P2X and 5-HT3 receptors.
- Paul Bertrand, Laboratory Chief
- Kate Polglaze, Associate Lecturer / PhD student (RMIT)
- Erica Diezmos, PhD student (UNSW)
- Grace Zhang, PhD student (UNSW)
- Zakiah Abdullah, BSc project, Temasek Polytechnic, Singapore
Past laboratory members
- Ms Danqing Lin (2014). RMIT University, School of Medical Sciences, Laboratory Medicine project
- Ms Chae Lim (2012 - 2014). MSc. Department of Physiology, UNSW
- Dr Sevvandi Senadheera (2008 - 2014). Departments of Physiology and Pharmacology, UNSW
- Dr Youngsoo Kim (2007 - 2015). Department of Physiology, UNSW
- Canada: A/Prof Lomax, A/Prof Beyak and Prof Vanner; Queen's University
- Germany: Prof Schemann and Dr Michel, Technische Universität München
- USA: Prof Galligan; Michigan State University
- Australia: Prof Bornstein (UniMelb), Dr Liu, Dr Murphy, Prof Housley, Prof Cook and Prof King (UNSW); Dr Chen (UTS); A/Prof Sandow (USC)
- RMIT: Dr Jenkins, Dr Walduck and Dr Istivan
- NHMRC Project grant. Liu, Bertrand and Sandow (2013-2015)
- NHMRC Project grant. Bornstein, Thomas, Parry and Bertrand (2009-2013)
- NHMRC Project grant. Bertrand and Liu (2008-2010)
All research projects are suitable for Project students, Honours or MSc/PhD candidates. Details of any projects are by negotiation with Dr Bertrand.
1. Mechanisms controlling 5-HT release from the gastrointestinal tract
This project is characterising the release of 5-HT (serotonin; 5-hydroxytryptamine) from the gastrointestinal neuroendocrine cells known as enterochromaffin cells (EC cells). Evoked release of 5-HT from EC cells is a critical step in the sensory transduction of chemical and mechanical information from the lumen of the gut. Alterations in the synthesis, storage or release of 5-HT can cause or exacerbate disease. Despite this, little is known about how EC cells respond to stimuli and how 5-HT is released from the intact organ. This project will use a novel real-time electrochemical technique to measure 5-HT release selectively, from intact preparations of the GI tract. The control of release by mechanosensitive channels such as ASIC and TRPA1 as well as nutrient and tastant sensing TRP channels will be investigated.
Collaborators: Dr Liu and Prof King (UNSW)
2. Correlating 5-HT release in human bowel diseases
In Inflammatory Bowel Disease (IBD) or functional bowel disorders such as Irritable Bowel Syndrome (IBS), there are profound changes in the content, release and reuptake of 5-HT (i.e., 5-HT availability). This project will look at the release of 5-HT on the same time scale that it is occurring and at the site of action in the intestinal lumen. For this purpose, a new sensor will be developed that has the potential to be embedded in an experimental endoscope suitable for use in patients. These experiments will be run in parallel with data gathered using traditional carbon fibre electrodes to analyse biopsy and surgical samples from patients. Finally, we will use mouse models of DSS-induced colitis and gastritis brought on by H pylori infection to analyse the potential pro-inflammatory role of 5-HT acting at 5-HT1A and 5-HT7 receptors.
Collaborators: Dr Anna Walduck, A/Prof Alan Lomax, Prof Steven Vanner, A/Prof Mike Beyak, Dr Lu Liu and Prof Denis King
3. Targeting 5-HT receptors to reduce obesity and improve blood glucose
Type 2 diabetes is becoming increasingly common. As such, there is an intensive search for new therapeutic agents to either treat or manage the condition. Cinnamaldehyde, a compound derived from cinnamon, is showing promise in animal models at reducing hyperglycaemia and weight gain. However, cinnamaldehyde also slows gastric emptying. This could be a problem for its use in 30% of patients with diabetic gastroparesis. We will determine if this effect can be separated from the more beneficial ones so that cinnamaldehyde or a derivative may be used without exacerbating the symptoms of gastroparesis. We hypothesise that cinnamaldehyde will cause a dose-dependent suppression of gastric emptying via TRPA1-mediated 5-HT release, with a concentration-dependent effect of 5-HT on gastric motility. At lower concentrations, 5-HT will promote gastric emptying via activation of 5-HT4 receptors, while at higher concentrations, 5-HT3 receptor activation will inhibit motility. To address this, we will look at gastric emptying in the intact mouse model of gastroparesis and at 5-HT receptor and TRPA1 activation and blockade using in vitro mouse stomach and human biopsies from patients with diabetic gastroparesis. We will also examine the activation of the enteric neurons by 5-HT3 and 5-HT4 receptors using a novel voltage-sensitive dye approach.
Collaborators: Dr Hui Chen, Dr Trisha Jenkins, Prof Schemann and Dr Michel
4. Isolation of EC cells and crypts to examine the biophysics of 5-HT release
In this project, we will investigate the regulation of 5-HT release from EC cells using state-of-the-art electrochemical methods combined with pharmacological and neurophysiological tests. This will allow us to investigate the control of 5-HT release in real-time, at the site of action and from only a few EC cells. We will record 5-HT release a) from in vitro preparations (where the EC cells have their normal complement of receptors and ion channels), b) from isolated crypts (containing only a few EC cells which have been minimally disrupted) and c) from enriched populations of dispersed EC cells (where single EC cells can be examined, but cell receptor/channel complements may be changed). In each condition, one or two small carbon fibre electrodes will be used to record from only a few intestinal EC cells at a time. We will compare the properties of release in these three paradigms by looking at time course, rundown and summation of 5-HT release events and by looking at control of release by blocking voltage-gated ion channels. This will allow us to determine whether 1) these preparations are physiologically equivalent and 2) whether there are distinct, functional sub-populations of EC cells.
Collaborators: Dr Lu Liu
Why not join us?
All enquiries about joining this research area as honours and postgraduate students or as post-doctoral fellows should be directed to Paul.Bertrand@rmit.edu.au.