The PE and PPE proteins of Mycobacterium tuberculosis and Mycobacterium bovis: exploring their potential as variable antigens. (360G-Wellcome-078256_Z_05_Z)

£490,127

The PE and PPE proteins of Mycobacterium tuberculosis and Mycobacterium bovis are encoded by large, multigene families which account for approximately 10% of the genome. Although the function of these proteins remains unclear, they are widely speculated to represent a source of antigenic variation, and thus a means for these pathogens to evade host immune defences. The overall aim of the proposed study is to determine whether the PE/PPE proteins do indeed represent variable antigens. Specifically, I will test the hypothesis that the pattern of PE/PPE expression changes during the course of infection and that this in turn modulates the host immune response. After characterising PE/PPE expression profiles in vitro, I will use two experimental models: infection of mice with M. tuberculosis, and infection of cattle with the closely-related M. bovis to examine in vivo expression and T cell recognition. These models are well-established in the sponsoring and collaborating laboratories and there is evidence in both systems that the bacterial phenotype and the immune repertoire change over the course of infection. In parallel with this in vivo approach, I will investigate the control of PE and PPE expression by identification and characterization of relevant transcriptional regulators in M. tuberculosis.

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Grant Details

Amount Awarded 490127
Applicant Surname Sampson
Approval Committee Basic Science Interview Committee
Award Date 2005-12-13T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Research Career Development Fellowship
Internal ID 078256/Z/05/Z
Lead Applicant Prof Samantha Sampson
Partnership Value 490127
Planned Dates: End Date 2010-05-31T00:00:00+00:00
Planned Dates: Start Date 2006-02-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Douglas Young