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Host-microbiome interactions in gut pathology icon

Overview

The intestine is host to a huge density of microorganisms collectively known as the gut microbiome. Multiple studies support alterations to the gut microbiome in intestinal diseases including inflammatory bowel disease (IBD) and colorectal cancer (CRC) although the direction of effect of these changes and the specific mechanisms that impact host physiology and pathophysiology are not well undertstood. We aim to understand how microbes and microbe-derived metaboiltes interact with the host and are capable of driving intestinal disease in the context of either host genetic defects or environmental perturbation.

Current projects

1. The impact of malnutrition on pathogen-induced intestinal disease

We are focusing on the determination of reciprocal impacts of malnutrition and intestinal infection with bacterial and protozoal pathogens. The aim is to define mechanisms underlying the relationship between malnutrition and increased susceptibility to diarrhoeal disease, impaired oral vaccine efficacy, and Environmental Enteric Dysfunction (EED) with the goal of testing new novel therapeutic approaches.

 

2. Antigen presentation and T cell regulation by intestinal epithelial cells

A single layer of intestinal epithelial cells (IECs) separates the mucosal immune cell compartment from the microbiota present in the intestinal lumen. IECs help to maintain immune homeostasis and loss of epithelial barrier integrity may contribute to the breakdown of intestinal homeostasis observed in certain intestinal inflammatory disorders, such as inflammatory bowel diseases. IECs express the antigen processing and presentation machinery, which evokes the question whether they can function as non-conventional antigen-presenting cells. My project aims to understand how antigen presentation by IECs contributes to intestinal homeostasis and intestinal inflammation.

 

3. Exploring longitudinal dynamics of the microbiome during gut inflammation

In this project we are focusing on defining compositional changes in intestinal microbial abundance and metabolic output over the course of colitis with the overall aim to manipulate the microbial components to prevent the development of colitis. To achieve this, our work adopts a multi-disciplinary approach, namely, multi-omic analyses and anaerobic and traditional culturing systems. Ultimately, this work may serve as a basis for future microbiome-based IBD therapeutics.

 

4. Alpha kinase 1: a novel kinase that acts as a checkpoint in controlling gut inflammation.

The development of colitis depends on genetic background, microbes and environmental factors. Genetic and functional studies in models and in IBD patients suggest that there is a malfunctioning checkpoints that control the host-microbiome interface. Alpha protein Kinase 1 (ALPK1) is responsible for the recognition of bacterial sugar metabolites, and it is a master regulator of innate immunity against Gram-negative bacteria such as Helicobacter pylori, Shigella flexneri, and enterotoxigenic Escherichia coli. We know that Alpk1 deficiency enhances colitis in model systems. However, how bacterial components interact with the malfunctioning host Alpk1 checkpoint remains unknown. In this project we utilise in-vivo and in-vitro models to directly identify the physiological and pathophysiological relevance of this novel inflammatory checkpoint.

Our team

Selected publications