The effective control of tuberculosis (TB) has been thwarted by the need for prolonged, complex and potentially toxic drug regimens, by reliance on an inefficient vaccine and by the absence of precise surrogate biomarkers of clinical status.
Failure to progress on each of these fronts can be attributed to the complex natural history of tuberculosis and to the lack of small animal models that accurately simulate all stages of the infection in humans. These impediments limit current knowledge about the biochemical pathways, physiological adaptations and immunological mechanisms necessary for the survival of the organism in human tissue. These deficiencies stand in marked contrast to achievements in genome science, including completion of the entire genome sequence of Mycobacterium tuberculosis (MTB), the causative agent of TB, and the development of new bioinformatics tools and gene expression methods. Together, these technological advances have accelerated new drug targets, immunizing antigens and biomarkers.
The promise of the genomics era for TB control is substantial, but is currently hobbled by failure to collect and integrate all relevant information about this organism at a single site in a way that can be readily accessed and analyzed by the experimental scientist. This unmet need is addressed in this proposal through the development of TBDatabase.
In its final form, TBDatabase will contain the experimental data, linked to databases and bioinformatics tools required to drive the drug discovery, vaccine and biomarker missions that are so crucial for TB control. Among its many capacities TBDatabase will store genomic expression data and genomic sequence data, as well as provide an effective user interface to analyze these data. A single system, accessible from a web portal will also query other databases crucial for drug, vaccine, and biomarker development.
This work supports the following GCGH grants: