Microbiome

Host-Microbial Interactions

Microbial factors that influence host immune responses

Interactions between microbiota and the host are critical for both homeostatic and pathological immune processes, particularly in the intestine. But how does this complex system work? To better understand the cross-talk between bacteria and host cells in the intestine, we are pursuing several avenues of investigation.

We are identifying and characterizing specific bacterial factors with immune function using epithelial cell lines, organoids, and myeloid cells from both humans and mice.

Current projects include

• Identification and characterization of immunomodulatory factors derived from Helicobacter hepaticus, a murine commensal pathobiont that is a key instigator of inflammation in mouse models of colitis.
• Characterization of bacterial metabolites that modulate the anti-microbial behaviour of human myeloid cell populations. 

Techniques

• Models of inflammatory bowel disease 
• Gene expression profiling 
• Bacterial killing assays

Microbial Community Profiling

The gut microbiota is altered in IBD relative to healthy individuals. How does this evolution of the gut microbiota take place? The combination of metagenomic and metatranscriptomic profiling of the gut microbiota enables us to assess changes in both bacterial community structure and transcriptional activity in mouse models of colitis.

Current projects include

• Deep sequencing of the metagenome and metatranscriptome during disease onset and resolution

Techniques

• Mapping reads to functions using bioinformatic tools 
• Microarray data with gene expression 

Host Transcriptomics

IBD represents a multifactorial disease with contributions both from environmental factors and genes. Host genetic variation in pathways regulating the microbiota, i.e. controlling host response pathways towards bacteria or impacting on barrier function, predisposes to chronic inflammation.

Current projects include

• Integrated host and microbiome profiling 
• Investigation of inflammation-driven changes to host pathways that may contribute to the observed alterations in the microbiota.

Techniques

• Models of inflammatory bowel disease 
• Gene expression profiling 
• Polychromatic flow cytometry, cell sorting and ex vivo analysis
•  In vitro primary cell differentiation and characterisation