Johnson Group | Microbiome and Multi-omics
Applying multi-omic and computational genomic approaches to understand the molecular basis of host-microbiome interactions
The human microbiome is the term used to describe the bacteria and other microorganisms that live on, and in, the human body. These microorganisms coexist with us, they are with us from birth, and they play an important role in shaping our immune system.
Research in the Johnson lab applies multi-omic and computational genomic approaches to understand how environmental factors, such as diet, impact on the composition of the human gut microbiome and how this in turn shapes host-microbiome interactions that are relevant to health and disease.
Through close collaboration with the Oxford Centre for Microbiome Studies we seek to bring observations from human studies into gnotobiotic experimental frameworks, where the role of specific microbes can be further dissected and understood.
The Microbiome and Metabolic Disease
We are interested in understanding how variation in the human gut microbiome may contribute to the onset and development of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2D).
Working with Professor Nita Salzman (Medical College of Wisconsin) and the Non-alcoholic Steatohepatitis Clinical Research Network we previously identified microbiome signatures associated with steatohepatitis and fibrosis in children with NAFLD (Schwimmer et al. 2019). We are currently using sequencing and bioinformatic approaches to further characterise the metagenome and metatranscriptome of an enlarged paediatric NAFLD cohort and to identify the precise genomic origin of bacterial genes encoding pro-inflammatory products in the NAFLD gut.
The Microbiome and T cell Vaccine Response
We are interested in how alterations in the immune system as a consequence of vaccination impact the microbiome and, reciprocally, how variation in the microbiome may shape T cell repertoires in a manner that influences vaccine response.
In collaboration with researchers at the Oxford Vaccine Group and Jenner Institute we are working to characterize inter-individual variation in the human gut metagenome in ongoing trials of prophylactic and therapeutic T cell vaccines. We are concurrently using gnotobiotic models to explore the microbiome response to vaccination and better understand how variation in the microbiome may contribute to vaccine immunogenicity.
Understanding Microbiome Heterogeneity in Disease Models
Animal models are an essential part of medical research. However, the microbiome remains a largely-uncontrolled factor in most animal facilities and variation in the microbiome between facilities almost certainly impacts host phenotypes in ways that reduce experimental reproducibility.
As part of the MRC National Mouse Genetics Network we are seeking to understand variability in mouse microbiomes across the UK, with the goal of improving reproducibility in animal models of human genetic disease and better understanding how such models capture disease-relevant features of the human microbiome.