Infection Genomics

Infection Genomics

Infection Genomics

Our Approach

trichuris-muris.jpgDavid Goulding, Sanger Institute
Trichuris muris

The Infection Genomics Programme investigates the common underpinning mechanisms of evolution, infection and resistance to therapy in viruses, bacteria and parasites. The Programme also focuses on the genetics of host response to infection and the role of the microbiota in health and disease.

The Infection Genomics Programme:

  • uses pathogen genomics and phylogenetics to understand transmission and evolution of diverse pathogens, and to discover determinants of host-interaction, virulence and evasion of antimicrobial drugs and vaccines.
  • uses host genetics in natural populations and engineered variation in model systems to identify variants underlying resistance and susceptibility to infectious agents, and validate these in model organisms and cellular systems.
  • combines variants from pathogen and host to interrogate host-pathogen interactions using functional genomic approaches.
  • uses metagenomics, large-scale culture and model murine systems to define the role of the microbiota in infectious and inflammatory diseases, particularly of the gut.
  • investigates the biology of the immune system in response to natural and vaccine stimulation.
  • develops tools and reference data sets (annotated genomes and functional genomics) for neglected and fastidious pathogens to enable research within and outside the Institute, with a focus on experimental manipulation and surface-protein interactions in Schistosoma and Trichuris.
  • focuses on the genetics and molecular biology of antimicrobial resistance, an area of key global concern, investigating common underpinning mechanisms of resistance to therapy.
Our Work
smansonipic.jpg
Schistosoma mansoni

We use large-scale pathogen genomics, analysing well-characterised population samples to discover the genetic basis of key phenotypes including host adaptation, virulence, transmission and escape from therapy. We incorporate novel microbial genetic association studies and use high-throughput approaches to validate pathogen phenotypes. We interrogate the contribution of the microbiota to health and disease using clinical samples, novel microbial culturing methods and germ-free models. We are establishing a project to understand the molecular basis of antibiotic resistance that will exploit microbial phylogeny and high-throughput phenotyping.

Our research in the host uses in vivo screens linked to human studies to identify and characterise novel host infection susceptibility loci for microbe-associated diseases. This Project employs targeted mutagenesis, humanised mice (genetics and microbiota) and single-cell genomics to analyse the effect of host variation on microbial infection. We are working closely with the Cellular Genetics Programme to model infection using human stem cell biology and associated differentiation and mutagenesis technologies. We contribute specific models (macrophages and organoids) and infection screens to that programme, and use these models in our own characterisation of susceptibility loci.

We are developing our vaccine-related research by focusing on the humoral immune response in terms of repertoire analysis and work on antibody function, linked to clinical studies on vaccination and pathogen challenge. This work draws on our links with the vaccine industry and the availability of modified mice harbouring genes encoding entire human antibody repertoires.

We analyse complex parasite genomes to provide high-quality reference genomes, and develop functional genomics (transcriptomics, mass spectrometry, recombinant protein libraries, host receptor identification etc.) for selected pathogens including Schistosoma and Trichuris. We have established components of the life cycle of these parasites in our laboratories to facilitate functional studies. We are creating sequence-based methodologies for characterising fastidious organisms present in complex materials, including clinical swabs and the environment.

To deliver our science, we work closley with the Human and Cellular Genetics Programmes and with key collaborators in UK Universities, the Wellcome Trust Overseas Units, and vaccine companies including The Hilleman Laboratories. We support the Centre for Genomic Pathogen Surveillance and UK health authorities in the clinical implementation of genomic approaches.

In addition to our core faculty, listed below, we also work with others including:

International Faculty:

Samuel Kariuki

Associate Faculty:

Bob Hancock

and Honorary Faculty:

Stephen Baker

Ian Humphries

Chris Newbold

Sharon Peacock

Research

Individual research projects are described on the faculty group pages below. Tools, data, and resources generated by the programme are:

Groups

The work of the Programme is delivered through Faculty members and their teams working across multiple projects to ensure cross-fertilisation of ideas, techniques and results.
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