Systems Biology Approach to the Mechanisms of TB Latency and Reactivation (R01)

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Purpose. The National Heart, Lung, and Blood Institute solicits Research Project Grant (R01) applications under this funding opportunity announcement (FOA) to investigate the mechanisms of latency and the reactivation of tuberculosis in the host using integrated systems biology approaches. Systems biology is defined in many ways. For the purposes of this FOA we are using a definition found on the MIT CSBi website: research program that links biologists, computer scientists, and engineers in a multi disciplinary approach to the systematic analysis of complex biological phenomena. The studies should include multiscale computational modeling and focus on host lung responses to Mycobacterium tuberculosis (Mtb) and host-microbial interactions that drive latency and reactivation in humans. To build the theoretical models, human and animal data should be utilized. The studies should integrate the data obtained from omic approaches with biological/immunological data. The models should be such that they can be tested in humans or non-human primates. The use of human samples and or data is required. Applicants are strongly encouraged to use the multiple principal investigator mechanism to facilitate collaborations among investigators with expertise in mathematics and computational multiscale modeling and clinical investigators and experimental biologists who have expertise in tuberculosis, pulmonology, lung biology, immunology, microbiology, genomics, genetics, other omics, and infectious diseases. Applicants are also strongly urged to include bioengineers and physicists in the research groups to enable teams of investigators to take advantage of new and developing technologies likely to be needed both to obtain biological data for building the computational models and for testing hypotheses generated by them. This FOA solicits applications for the TB Systems Biology Centers and runs in parallel with a separate FOA that solicits applications for a Data Coordinating Center (see RFA-HL-10-022).

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