Douglas Young

Mycobacterial Systems Biology Laboratory 

One third of the global population is exposed to infection with Mycobacterium tuberculosis but only 10 per cent 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 interested in studying the ways in which Mycobacterium tuberculosis has co-evolved with humans over the last 70,000 years. Clonal evolution of M. tuberculosis in the absence of horizontal gene transfer makes it relatively straightforward to document the sequence of mutations that have occurred since the initial infection of early modern humans in Africa, and to relate these to patterns of human migration and changing demography. The challenge is to distinguish the limited set of functionally relevant mutations from background random genetic diversity.

We are approaching this using a systems biology approach to allow sequential identification of SNPs that have a phenotypic impact at the level of transcriptome, proteome and metabolome. We anticipate that this will provide fundamental insights into fine-tuning of host-pathogen interactions at the interface between commensal infection and disease, and may help in the design of future strategies to prevent emergence of novel pathogenic interactions in the context of changing human demography and social structure.

Global phylogeny of M. tuberculosis

Global phylogeny of M. tuberculosis (Click to view larger image)

Phenotypic characterisation of M. tuberculosis using genome-based 'omic technologies uncovers an extensive network of non-coding RNAs and a high percentage of leaderless transcripts indicative of an important level of post-transcriptional regulation.

By understanding the molecular pathways that underpin the pathogenesis of M. tuberculosis we aim to be able to design improved future strategies for disease control.

Selected publications

Firdessa R et al. 2013. Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia. Emerging Infect Dis 19:460-463. PMID: 23622814

Comas I et al. 2013. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nat Genet 45:1176-82. PMID: 23995134

Rose G et al. 2013. Mapping of genotype-phenotype diversity among clinical isolates of Mycobacterium tuberculosis by sequence-based transcriptional profiling. Genome Biol Evol 5:1849-62. PMID: 24115728

Cortes T et al. 2013. Genome-wide mapping of transcriptional start sites defines an extensive leaderless transcriptome in Mycobacterium tuberculosis. Cell Rep 5:1121-31. PMID: 24268774

Esmail H et al. 2014. The ongoing challenge of latent tuberculosis. Philos Trans R Soc Lond B Biol Sci 369:20130437. PMID: 24821923

Douglas Young

douglas.young@crick.ac.uk
+44 (0) 20 8816 2657

  • Qualifications and History
  • 1978 DPhil University of Oxford, UK
  • 1978 Post-doctoral Fellow, Foundation for Medical Research, Mumbai, India
  • 1980 Post-doctoral Fellow, London School of Hygiene and Tropical Medicine, UK
  • 1982 Assistant Professor, University of Washington, Seattle, USA
  • 1985 Career Scientist, MRC Tuberculosis and Related Infections Unit, London, UK
  • 1993 Fleming Professor of Medical Microbiology, Imperial College London, UK
  • 2007 Head of Division of Mycobacterial Research, Medical Research Council National Institute for Medical Research, London, UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK