Group members

Dr Brian D Robertson
(Principal Investigator)
b.robertson@imperial.ac.uk

Professor Douglas B Young
(Principal Investigator)
d.young@imperial.ac.uk

Dr Iria Uhia Castro
(Visiting Research Associate)
i.uhia-castro@imperial.ac.uk

Dr Nitya Krishnan
(Research Associate)
nitya.krishnan@imperial.ac.uk

Miles Priestman
(Research student)
m.priestman13@imperial.ac.uk

Dr Vani Subbarao
(Research student)
sathyavani.subbarao@imperial.ac.uk

Collaborators

Dr Guy Thwaites
(Visiting Researcher)
g.thwaites@imperial.ac.uk

Tuberculosis research group

Mycobacterium tuberculosis is one of mankind’s most successful pathogens: around 8 million people develop tuberculosis every year, and 1.5 million people die. Most people mount an immune response that is sufficient to control initial infection but they remain susceptible to reinfection or reactivation disease in later life. Immunological evidence suggests that up to two billion people worldwide may harbour latent tuberculosis, with a ten percent lifetime risk of developing active disease. In 2006 the Stop TB Partnership set out a Global Plan to Stop TB, with the aim of cutting prevalence and mortality in half by 2015, as a step towards elimination of TB as a public health problem by 2050. Development of improved drugs, diagnostics and vaccines is central to the Global Plan, which has been updated several times and now covers 2016 to 2020.

The aim of our research is to understand the host-pathogen interactions underlying the complex biology of tuberculosis infection, and to exploit this understanding for development of improved tools for disease control. Our research is driven by genome-based biology, taking advantage of the availability of mycobacterial sequence data, techniques for mutagenesis, expression profiling and analysing transcription factors, and the natural diversity of clinical isolates. Analysis and integration of large amounts of data on host and pathogen responses to infection is increasingly dependent on the emerging discipline of Systems Biology and we work closely with the Centre for Integrative Systems Biology and Bioinformatics CISBIO.

New drugs for TB

There is an urgent need for new drugs to combat the progressive development of antimicrobial resistance amongst clinical isolates of M. tuberculosis. Current drugs are effective against actively replicating bacteria, but have to be administered for six months in order to prevent reactivation in patients with active disease or in individuals with latent infection. This is thought to be due to persistence of a sub-population of non-replicating, phenotypically-tolerant bacteria. Characterisation of the phenotypic characteristics of M. tuberculosis during active and latent infection was a central component of a major international collaborative project to develop “Drugs for Treatment of Latent Tuberculosis” jointly funded by the Bill & Melinda Gates Foundation and the Wellcome Trust as part of a programme to address Grand Challenges in Global Health.

Recent PhD projects have included regulation of nitrogen assimilation in mycobacteria, IL-1 beta and the inflammasome, and mycobacterial cell division and the bioogy of persisters, which involved establishing time-lapse microscopy for this slow growing organism. Bioluminescent imaging of mycobacteria was established as part of a Bill and Melinda Gates Foundation funded consortium and this work is now being applied to image the in vivo efficacy of anti-bacterial drugs administered by different routes and in different formulations. We are part of a consortium using some of these imaging tools to develop a human challenge model for TB vaccination, funded by Aeres

There is an urgent need for new drugs to combat the progressive development of antimicrobial resistance amongst clinical isolates of M. tuberculosis. Current drugs are effective against actively replicating bacteria, but have to be administered for six months in order to prevent reactivation in patients with active disease or in individuals with latent infection. This is thought to be due to persistence of a sub-population of non-replicating, phenotypically-tolerant bacteria. Characterisation of the phenotypic characteristics of M. tuberculosis during active and latent infection was a central component of a major international collaborative project to develop “Drugs for Treatment of Latent Tuberculosis” jointly funded by the Bill & Melinda Gates Foundation and the Wellcome Trust as part of a programme to address Grand Challenges in Global Health.

Recent PhD projects have included regulation of nitrogen assimilation in mycobacteria, IL-1 beta and the inflammasome, and mycobacterial cell division and the bioogy of persisters, which involved establishing time-lapse microscopy for this slow growing organism. Bioluminescent imaging of mycobacteria was established as part of a Bill and Melinda Gates Foundation funded consortium and this work is now being applied to image the in vivo efficacy of anti-bacterial drugs administered by different routes and in different formulations. We are part of a consortium using some of these imaging tools to develop a human challenge model for TB vaccination, funded by Aeres.

The immune response to TB

We are testing the hypothesis that initial recognition of M. tuberculosis by the innate immune system is a crucial stage in the pathogenesis of disseminated disease, by comparing responses to strains that are preferentially associated with pulmonary TB or TB meningitis in Vietnam. We are also looking at the kinetics of M. tuberculosis dissemination from the site of infection in model systems, and in parallel measuring cytokine levels in tissues to provide a quantitative assessment of local and regional T-cell mediated immunity. This has shown a key role for IL-1beta, a topic that is being further explored, alongside other key modulators of the inflammatory response to tuberculosis infection.

Tuberculosis journal

Brian Robertson is an Editor in Chief, and Douglas Young is Consulting Editor of the journal Tuberculosis. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism. Instructions on submission of manuscripts are provided on the website.

The Tuberculosis group is led by Dr Brian Robertson, and is closely linked with the Francis Crick laboratories at Mill Hill, led by Professor Young.

XDRTB.org, creating awareness of extremely drug resistant TB.

XDRTB.org is an extraordinary effort to tell the story of extremely drug-resistant tuberculosis (XDR-TB) and TB through powerful photographs taken by James Nachtwey, who has been covering war and human rights stories for 30 years. In 2007, he was awarded the TED Prize, which comes with $100,000 and one wish to change the world. These photographs and this project are his wish. http://www.xdrtb.org/