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Identification and characterization of Mycobacterium tuberculosis virulence genes involved in macrophage parasitism

Project information

Grant agreement ID: 37732

  • Start date

    1 October 2006

  • End date

    30 September 2009

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 1 168 214

  • EU contribution

    € 734 713

Coordinated by:

THE UNIVERSITY OF SURREY

United Kingdom

Objective

Mycobacterium tuberculosis is a leading threat to human health, killing 40,000 people a week and causing 8 million new cases of disease every year. Current vaccination and chemotherapy strategies are unsatisfactory making development of novel control strategies an important objective. Rational design of such strategies requires an understanding of the mechanisms by which M.tuberculosis is able to infect individuals and cause disease. Central to the success of M.tuberculosis as a pathogen is an ability to replicate inside the normally destructive phagosomal compartments of macrophages.
TB-MACS proposes to use innovative genetic screens to reveal the genetic and mechanistic basis of this characteristic. Specifically TB-MACS will use microarray based screening of an M.tuberculosis mutant library in two separate selections to identify mutants that are unable to nhibit phagosome acidification and/or unable to inhibit fusion of the phagosome with hydrolytic lysosomes.
Mutants identified in these assays will be isolated and characterised with respect to intracellular trafficking and growth in human macrophages. The in vivo phenotypes of the phagosome mutants will be assessed in murine and guinea pig models of tuberculosis.
To begin to understand the mechanisms encoded by the mutated genes, TB-MACS will make a detailed examination of the proteomes and transcriptomes of selected mutants. TB-MACS brings together three laboratories with complementary skills and facilities in high-throughput genetic screening, flow-cytometry, cell biology, transcriptomics and proteomics - the net result of which is a unique project that is able to provide system-wide answers to important unanswered questions about M.tuberculosis virulence. TB-MACS will contribute to improving human health by defining bacterial products and processes that are essential to infection and which will be useful in the rational development of new drugs and vaccines against tuberculosis.

Coordinator

THE UNIVERSITY OF SURREY

Address

Stag Hill
Guildford, Surrey

United Kingdom

Participants (4)

INSTITUT PASTEUR

France

ID-LELYSTAD, INSTITUUT VOOR DIERHOUDERIJ EN GEZONDHEID BV

Netherlands

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

France

STICHTING DIENST LANDBOUWKUNDIG ONDERZOEK

Netherlands

Project information

Grant agreement ID: 37732

  • Start date

    1 October 2006

  • End date

    30 September 2009

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 1 168 214

  • EU contribution

    € 734 713

Coordinated by:

THE UNIVERSITY OF SURREY

United Kingdom