Glial-immune interactions in the gastrointestinal tract: protection against inflammation and cancer

One of the main tasks of the immune system is to appropriately react to “danger” or “non-danger” signals. This is even more relevant in the intestine, where immune cells are constantly presented with foreign substances as food.

Hence, the balance between immune activation versus tolerance should be tightly regulated to maintain intestinal homoeostasis and to prevent indiscriminate immune activation against the gut content. Loss of this delicate equilibrium results in many intestinal disorders such as inflammatory bowel disease. To better understand how intestinal homoeostasis is preserved, we will investigate how immune responses are modulated and controlled in the gut.

In this project, we will examine the role of an important player in this system: enteric glial cells. Enteric glial cells, the prevalent constituent of the nervous system in the gut wall, have been traditionally considered only as supportive cells surrounding enteric neurons. Using a novel experimental co-culture approach, we have obtained preliminary data showing that enteric glia can modulate the inflammatory response. However, how enteric glia communicate with the immune system remains still to be addressed. Understanding the molecular mechanisms by which mucosal immune cells and the enteric glia crosstalk in health and disease will help us to develop novel therapeutic strategies to treat intestinal immune-mediated diseases.

Project goals

To investigate how enteric glial cells influence gut immune function in two different models: inflammatory bowel disease and cancer. Inflammatory bowel disease (IBD) results from chronic inflammation of the digestive tract. Two major forms of IBD are Crohn’s Disease and Ulcerative Colitis, which are characterised by diarrhoea, rectal bleeding, and severe pain. These are debilitating chronic diseases with no clear, distinct causes or known cures. Glioma is the most prevalent malignant brain cancer. It arises from over-proliferation of glial cells in the brain. Tragically, the survival rate for gliomas remains low, with only 20% of diagnosed patients surviving beyond 5 years.

However, whilst there is a significant population of glial cells in the gut, there are very few cases of gliomas in the gastrointestinal tract.

• Intricate communication from enteric glia is crucial for modulating immune function, on the one hand, to prevent immune over-activation and inflammation, and on the other hand, for targeted attack of over-proliferating glial cells.
• Using a combination of our expertise and techniques, we aim to identify how enteric glial cells carry out these dual roles, and identify the mechanisms underlying glial-immune communication in the gut.

Supervision team

The University of Melbourne: Dr Marlene Hao

KU Leuven: Associate Professor Gianluca Matteoli

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Who we are looking for

Further details

The PhD candidate will benefit from the combined expertise of the project supervisors, and the embedding into two research environments.

Associate Professor Gianluca Matteoli will contribute his expertise in all aspects of mucosal immunology and enteric neuroscience as well as advanced single cell RNA techniques and flow cytometry. Dr Marlene Hao’s contribution is through her expertise in the enteric nervous system and enteric glial cells and techniques such as gut dissection and dissociation, isolation of specific cell populations including enteric glia, live calcium imaging, RNA isolation, gene expression analysis, as well as immunohistochemistry and confocal microscopy. For this particular project she will focus on techniques for assessing ENS function, including whole gut transit, colonic motility mapping and live calcium imaging.

This PhD project will be based at KU Leuven with a minimum 12-month stay at the University of Melbourne.

The candidate will be enrolled in the PhD program at the Department of Chronic Disease, Metabolism and Ageing at KU Leuven, and in the PhD program at the Department of Anatomy and Physiology at the University of Melbourne.

To apply for this joint PhD opportunity, and to view the entry requirements, visit the How to Apply.