In vitro modelling of nutritional, microbial & immune cell interactions at the human gut epithelium
Dr Claire Bourke
In vitro modelling of nutritional, microbial & immune cell interactions at the human gut epithelium
The gut epithelial barrier adapts to malnutrition, which spans undernutrition (stunting, wasting), overnutrition (overweight, obesity) and micronutrient deficiency. This has implications for gut physiology, permeability and the cell types and locations that are exposed to dietary metabolites, commensal microbes, enteropathogens and their antigens. Dysfunction at the gut epithelial barrier, sometimes called 'leaky gut', can lead to systemic activation of immune cells and the chronic inflammatory state that characterises most forms of malnutrition. This project will develop culture-based models of the human gut barrier, aiming to incorporate epithelial cells, endothelial cells and immune cells. Barrier function will initially be assessed using a transwell culture system to determine the effects of different conditions associated with malnutrition (e.g. nutrient content of culture media; microbial antigens and metabolites; cytokines and chemokines associated with anti-pathogen defence and barrier homeostasis). The project will build towards development of: 1) culture-based tools to screen functional effects of blood, stool and cellular samples from malnourished people, and, 2) development of more physiologically-relevant multicellular 3D models of the gut barrier to evaluate response to commensal and pathogenic microbes.
The rotation project would entail maintenance and culture of human epithelial, endothelial and immune cell lines to explore cell-type specific functions under different culture conditions. The student would then combine cell types into multicellular transwell models to explore how nutrients, pathogen associated molecular patterns (PAMP) and pro-inflammatory cytokines affect barrier function. They would develop skills in cell culture, immunology assays (ELISA, immunofluorescence microscopy, luminometry, flow cytometry) and experimental design.
Supervisors: Claire Bourke; Simon Milling
https://www.gla.ac.uk/schools/infectionimmunity/staff/clairebourke/
Twitter/X: @BourkeLab