Gut Research Unit (GRU)
We are interested in understanding how the normal human gut works and the processes that lead to diseases such as Crohn’s and Ulcerative colitis.
Our vision and network
We are a ‘MELTING POT’ of researchers - immunologists, chemists, biologists, clinical trialists, clinicians and data scientists - with a shared vision to translate science to medicine.
We work closely with the Edinburgh IBD Science network, including clinical colleagues at the Western General Hospital and scientists at the Institute for Genetics and Cancer and Roslin Institute.
Our collaborative work spans across the Universities of Glasgow, Dundee and Napier with our recently formed Scottish Translational Gut Research (STAR – led by Dr Ho) network that brings together a diverse community of researchers with an emphasis on developing world class science in Scotland.
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Our key research
Our highly collaborative and integrated scientific work has a strong focus on direct studies on human gut and immune cells kindly provided by our research participants; and new complementary experimental models such as organoids (‘miniguts on a dish’).
Current research projects
The role of ‘M’-cells in Crohn’s disease. M-cells are gatekeepers of the gut lining, allowing certain bacterial particles to pass in order to educate the immune cells. With Professor Neil Mabbott and our pathologists, Dr Kate Kirkwood, Dr Alex Cavanagh, we are studying how changes in M-cells and how this affects bacterial handling in the gut may lead to how gut inflammation develops in Crohn’s disease.
Using gut organoids to understand the role of mitochondria in maintaining gut health. Dr Duncan Rutherford, as part of his Chief Scientist Office PhD project is establishing ‘mini-guts’ grown from patients with in Inflammatory Bowel Disease. This forms our efforts to use primary human cells (rather than mouse models) to understand the function of our guts. We hope to build towards using gut organoids to directly repair the damaged IBD gut in the future.
GI-DAMPs – We are investigating how molecules released from the damaged gut lining (DAMPs) can trigger and maintain inflammation in IBD. We are finding ways to block these signals as potential new treatments in IBD. This focused cross-sectional study has recruited ~800 IBD patients across Scotland (target n=1500) with a deep clinical-science dataset to allow us to carry out detailed analyses on these new biomarkers. We (led Dr Rahul Kalla) have received further funding from CCUK to use a protein-array panel using very small amounts of blood to track mucosal healing in IBD. (Gwo-tzer Ho).
IBD-IMAGE and IBD-Sense – We are designing new biomarker tests that can provide results instantly in the clinic, by emitting a fluorescent signal if certain signs of inflammation are present in IBD. Funded by successive ERC project grants and Scottish Enterprise, we have developed a IBD activity molecular probe based on Granzyme B which is about to be tested in the clinical setting. (Marc Vendrell).
FATE-CD – Led by Dr Rahul Kalla (Consultant Gastroenterologist and NRS Fellow), we are developing a human imaging based approach to detect early fibrosis in Crohn’s disease.
Monocyte-macrophage function in IBD - We are investigating how the macrophage population in gut can either worsen inflammation or begin the process of healing in Crohn’s disease. Macrophages are a type of immune cell. We are using a technique called single-cell RNA sequencing to study how these macrophage populations change when Crohn’s disease is diagnosed, initially treated and ultimately healed over time. This will allow us to identify new drug targets or cell-based treatments in Crohn’s disease. (Calum Bain, Gareth Jones).
Anti-microbial peptide, LL-37 and T-cell function - We are investigating how a natural anti-microbial peptide LL-37 produced by our gut directs the migration of inflammatory T-cells to the gut lining in Crohn’s disease. Funded by MRC Program grant for Dr Emily Findlay, our work is beginning to map Th17 responses and LL-37 along the gastrointestinal tract (Emily Findlay).
Prostaglandin E2 and its receptor EP4 in Crohn’s disease - We are investigating how the production of prostaglandins can change how the immune cells function in Crohn’s disease. Prostaglandins are molecules that can both protect the gut lining and bring about inflammation. Of interest, PTGER4 gene that encodes the EP4 receptor is one of the strongest genetic factors in Crohn’s disease (Chengcan Yao).
Targeting the neutrophils in IBD - We are finding new ways to reduce the damaging potential of the neutrophils (the ‘first responders’ of inflammation) in order to accelerate the healing process of the gut in IBD (Adriano Rossi and Gwo-tzer Ho).
Mitochondria and IBD – Mitochondria produce energy in the cell. They are also important in the health of our gut barrier function and can determine whether immune cells behave in a pro- or anti-inflammatory manner. Several lines of research are ongoing with a main focus on the role of short fragmented mitochondrial DNA on immunity and modulation of mitochondrial function in intestinal stem cells during gut repair and inflammation (Gwo-tzer Ho).
Gut microbiome and mucosal healing in IBD – Working with collaborators in Royal Hospital of Sick Children Edinburgh and Universities of Glasgow and Dundee (David Wilson, Konstantinos Gerasimidis, Richard Hansen and Craig Mowat), we are developing a new area of research to understand how the gut microbiome contributes to the healing of the gut lining in IBD. A particular focus is on the oral microbiome in adults and children with IBD, funded by MRC Precision Medicine and Edinburgh Sick Children fellowships to Mr Robert Whelan and Dr David Wands.
In the GRU, we have successfully taken basic science discoveries made in 2014-2018 to Phase 2b human clinical trials in IBD (2021-2024) in line with our 'Science-to-Medicine' vision.
MARVEL - In the MARVEL Phase 2b clinical trial, we investigate if MitoQ (mitochondrial-targeted anti-oxidant) helps in treating patients with ulcerative colitis (UC). The MiniMARVEL trial looks at use of the same treatment in children with UC. Together, they form the first ‘all-ages’ IBD clinical trial, recruiting adults and children simultaneously. These multi-centre studies are set to open across UK in 2021.
Find out more on the MARVEL website
MUSIC - In the MUSIC IBD Study, we are investigating how DAMPs or ‘danger signals’ can be used as a biomarker test for patients with Crohn's disease or Ulcerative colitis. A novel aspect of this study is its setup that provides ‘enhanced’ follow-up to our newly diagnosed patients with IBD. We are capturing the research experience of our study with our patient-led engagement groups.
This prospective longitudinal cohort study will study all established biomarkers in IBD patients, as well as experimental markers. Samples will be donated when the patients are diagnosed and when they receive medical treatments. Uniquely, we will study the usefulness of this scientific information in relation to how the gut lining heals in IBD. The MUSIC IBD Study is currently open in Edinburgh, Glasgow and Dundee in 2021 and we have recruited more than 100 patients in this in-depth study (www.musicstudy.uk).
In 2023, 4 key human translational studies, IBD-Sense (Granzyme B biomarker), FATE-CD (non-invasive imaging of fibrosis in Crohn’s disease), BIOPIC (Dietary intervention in Crohn’s disease patients; and MiniMUSIC (prospective paediatric IBD study in DAMP biomarkers) will be at the exciting stage of starting!
New focus on science and well-being in IBD
In 2022, we recently developed a novel line of work to study patient-reported outcomes on overall well-being and their relationship with known and new scientific biomarkers (led by Dr Rebecca Hall, clinical research fellow).
With Crohn’s Colitis UK, we are conducting the largest survey of well being (target 5000 responses) using validated IBD questionnaire to provide an objective benchmark of the hidden burden of IBD (during active disease and in remission) to our detailed clinical and scientific research work.
Survey accessed via https://forms.office.com/e/aJWUEC4UUN
Who we work with
Our funders and research partners help to make our research possible, supporting staff and students at the cutting edge of gut repair science and medicine.
Crohn's and Colitis UK (CCUK) are the UK's leading charity for Crohn's and Colitis, funding research and providing information for patients, friends and family, medical practitioners and employers about these conditions.
European Research Council (ERC) encourages the highest quality research in Europe through competitive funding and to support investigator-driven frontier research across all fields, on the basis of scientific excellence.
Helmsley Charitable Trust aspires to improve lives by supporting exceptional efforts around the world in health and select place-based initiatives.
Guts UK is the only UK charity funding research into the digestive system from top to tail; the gut, liver and pancreas.
The Jon Moulton Charity Trust seeks to fund non-commercial clinical trials with the aim to make clinical advances and promote the relief of suffering.
Medical Research Council (MRC) seeks to encourage and support research to improve human health, produce skilled researchers, advance and disseminate knowledge and technology to improve the quality of life and economic competitiveness of the UK, and promote dialogue with the public about medical research.
Wellcome supports science to solve the urgent health challenges facing everyone.
The Edinburgh IBD Unit
The Edinburgh IBD Unit is based at the Western General Hospital, comprising Professor Charlie Lees, Shahida Din MD (Gastroenterologist), Ian Arnott MD (Gastroenterologist) and Audrey Kuchnowski (Lead Clinical Research Nurse).
Involving patients and the public
Communicating with our patients and members of the public is a key part of our research process. We work closely with patient-centred charities and have an active Patient and Public Involvement (PPI) group led by Kris McGuire and Jon Rysdale.
The following animation, developed in collaboration with Edinburgh-based science animation company Cloud Chamber Studios, describes our work and how you can get involved.
- Video: Healing the damaged gut
- The Gut Research Unit at the Centre for Inflammation Research, University of Edinburgh, shares some of its work on healing the damaged gut in inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. Narrated by Dr Kris McGuire, a patient representative with the group.
CCUK's Patient Involvement Day in November 2021 ran virtually. Research Fellow, Michelle Wilson, presented a brief introduction to the new Mini-MARVEL study, which focuses on paediatric ulcerative colitis patients and can be viewed below.
- Video: Mini-MARVEL study - Michelle Wilson CCUK Patient Involvement Day 2021
- Michelle Wilson discussing the Mini-MARVEL paediatric ulcerative colitis at the Crohn's & Colitis patient day 2021.
CCUK's Patient Involvement Day in October 2020 was run virtually for the first time. Postdoctoral researcher Milly McAllister presented a virtual poster about her work on IBD biomarkers - specifically short protein strands produced by mitochondria, called 'mitochondrial formylated peptides' - which can be seen below.
- Video: PPI Day 2020 Virtual Poster
- Milly McAllister's virtual poster at the Crohn's and Colitis UK (CCUK) Patient Involvement Day 2020.
Our IRR Discovery Series video describes Thomas Fenton's work on isolated lymphoid follicles and how he discovered the micro-surgery technique used in the lab today.
- Video: IRR Discovery Series: Dr Thomas Fenton
- Dr Thomas Fenton, Visiting Scientist at the Centre for Inflammation Research, discusses a method he has developed which will give researchers a new way to analyse the intestinal immune system.
Our Let's Talk About Health lecture, delivered by Principal Investigator Gwo-tzer Ho, PhD student Emily Thompson and IBD patient Kris McGuire, talks about current work, what it's like to be in the lab day to day, and the importance of clinical trials from a patient perspective.
- Video: Healing the damaged gut in inflammatory bowel diseases
- A recording of the Let's Talk About Health public lecture given on 19 February 2020, talking about the perspectives of a medical researcher, IBD patient and PhD student on current IBD research at the Centre for Inflammation Research.
If you would like to get involved with our patient and public involvement groups as someone who lives with or alongside Crohn's and colitis, or is simply interested in research and clinical trials, do get in touch.
Contact CIR's Public Engagement & Communications
Herald article March 2021 - New genetic clues to Crohn's disease unravelled in Edinburgh hotspot
Herald article March 2021 - Crohn's disease ordeal for Edinburgh student who 'thought it was food poisoning'
There are currently no vacancies, but please check @EdinIBDScience twitter for updates.
Mitochondria and Inflammatory Bowel Diseases: Toward a Stratified Therapeutic Intervention. Ho GT and Thiess AL. Annual Review of Physiology 2022, 84, p 435-459.
Resolution of Inflammation and Gut Repair in IBD: Translational Steps Towards Complete Mucosal Healing. G-T. Ho et al. Inflammatory Bowel Diseases 2020, 26(8), p 1131-1143.
Barrier-tissue macrophages: functional adaptation to environmental challenges - A.M. Mowat et al. Nature Medicine 2017, 23, p 1258–1270.
Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell–IL-22 axis. R. Duffin et al. Science 2016, 351 (6279), p 1333-1338.
Biomarkers in Search of Precision Medicine in IBD. R. Boyapati et al. The American Journal of Gastroenterology 2016, 111(12), p 1682-1690.
Want to help?
If you're passionate about healing the damaged gut, you can support our research by making a philanthropic donation.
Get in touch with the Fundraise Your Way team