How disrupting our microbial partners can cause human disease?

The human gut microbiome represents a complex ecosystem contributing essential functions to its host. The complex assemblages of microorganisms which populate the human gastrointestinal tract are key players in human health and disease. The gut anaerobe Clostridium difficile is a leading cause of nosocomial diarrhoea and pseudomembranous colitis and is responsible for approximately 29,000 deaths per year in the United States; with an overall economic burden of infection estimated at US$ 5.4 billion per year.

Pathogenic microbes have evolved complex systems to colonise host environments. Elucidating how these systems function is critical for understanding the infection process and hence treatments.

Interactions of anaerobic gut bacteria with the intestinal mucosa have traditionally been poorly studied, in the main, due to challenges in culturing aerobic gut epithelium with anaerobic bacteria. Within this project we will utilise a novel human gut model; which allows human gut epithelial cells to be co-cultured within anaerobic gut bacteria. Utilising this system in conjunction with chemical biology techniques (bio-orthogonal noncanonical amino acid tagging (BONCAT) and Stable Isotope labelling by Amino Acids in Tissue Culture (SILAC)); aligned with proteomics and molecular biology we will reveal the molecular aetiology of gut colonisation by the anaerobic pathogen Clostridium difficile.

Specific skills/experience required by applicants:

A theoretical understanding of mass spectrometry and the techniques of BONCAT and SILAC are essential.

Mammalian cell culture and bacterial cell culture would be advantageous.