MRC National Institute for Medical Research, London

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Research areas

Genetics and Development

Infections and Immunity

Neurosciences

Structural Biology

Douglas Young group

Mycobacterium tuberculosis and the host response

One third of the global population is exposed to infection with Mycobacterium tuberculosis but only ten percent of individuals will develop tuberculosis. The outcome of infection depends on a complex series of interactions with the immune system, which can result in disease or persistence of the pathogen in an asymptomatic, latent infection. We are testing the hypothesis that the pathogen misleads the host into mounting a suboptimal response. Ultimately, we aim to develop drugs that rapidly eliminate persisting bacteria and vaccines that elicit more effective immunity.

Innate immune responses to M. tuberculosis involve recognition of molecules on the surface of the bacteria by receptors expressed on phagocytic cells. Variation in surface ligands expressed by M. tuberculosis strains from different phylogenetic lineages may cause differences in immune recognition and disease. By labelling with different fluorescent colours, we can follow multiple strains in mixed infection experiments. Strains also differ in the way they respond to the host. Using next-generation sequencing to screen the entire transcriptome of M. tuberculosis, we have identified a previously unknown repertoire of regulatory RNA molecules that vary between strains.

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Labelling with red and green probes allows us to compare the behaviour of different strains of M. tuberculosis during infection of host macrophages.

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Northern blot analysis shows differences in the expression of a small regulatory RNA molecule between different strains of M. tuberculosis.

Research projects

Gene expression and pathogenicity in mycobacteria - Roger Buxton

Selected publications

Arnvig, KB and Young, DB (2009)
Identification of small RNAs in Mycobacterium tuberculosis.
Molecular Microbiology 73, 397-408 PubMed abstract
Young, DB; Gideon, HP and Wilkinson, RJ (2009)
Eliminating latent tuberculosis.
Trends in Microbiology 17, 183-188 PubMed abstract
Young D, Stark J and Kirschner D (2008)
Systems biology of persistent infection: tuberculosis as a case study.
Nature Reviews Microbiol 6, 520-528 PubMed abstract