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MM-TB


Tuberculosis

Molecular Markers of M. tuberculosis Early Interactions with Host Phagocytes
Framework programme:
6
Call:
2
Project number:
LSHP-CT-2004-012187
EC contribution:
€ 976,000
Duration:
24 months
Type:
STREP
Starting date:
1 January 2005

Keywords: Immunology; vaccines; tuberculosis; mycobacteria; dendritic cells; macrophages; microarray; transcriptional profiling; database; vaccine

Summary:

Comparative genomics offers a highly innovative opportunity to decipher M. tuberculosis interactions with the immune system, using transcriptional profiling approaches. In particular, early interactions between M.tuberculosis and host phagocytes, namely macrophages and dendritic cells (DC), are thought to play a crucial role in mounting a protective immune response, and in determining the outcome of infection. Microarrays will be used to study simultaneously the entire expressed genomes of both the mammalian host and the microbial parasite during their interaction. Data analysis of the M. tuberculosis arrays, developed by the participants, will reveal patterns of the induced gene expression and, most likely, unique novel targets for vaccine design. Data analysis of mouse and human arrays (GeneChips by Affymetrix) of M.tuberculosis-infected monocytes and dendritic cells will allow identification of molecular markers and pathways associated with protection.
This STREP fully integrates the activities of internationally recognised groups that have pioneered the TB field and the development of M.tuberculosis arrays with groups that have developed immuno-genomics and, in particular, transcriptional profiling analysis of phagocytic cells. These groups will implement an IT-based integrated knowledge management system providing a new centralised European resource - a transcriptional TB databases. This transcriptional profiling database should have a major impact on the identification of new molecular markers and molecular targets, and will certainly support the recent European TB vaccine effort.

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