Understanding the dynamic interplay between tuberculosis and its host to reduce transmission

Project Team: Gordon Broderick, Neeraj Dhar, Jeffrey Chen, Pranta Saha, Joyce Reimer, Chris Chen (VIDO) and Selvakumar Subbian (Rutgers Health- New Jersey Medical School))

Mycobacterium tuberculosis (Mtb) is the causative agent in tuberculosis infection that is then transmitted to other hosts by coughing or sneezing. However, not much is known about the host or bacterial factors that contribute to driving this airborne spread.   We propose that a complex dynamic cascade of cellular and molecular events from initial Mtb infection to the formation of lesions, cell death and inflammation will contribute to the spread of infection within the host but also to transmission from one host to another. A major barrier to our understanding of these processes has been a lack of reliable translational models to study this progression to airborne transmission of Mtb.  In this study we bring together experts from multiple disciplines to collaborate in developing a framework that scales progressively and seamlessly from tissue culture to a small animal model (rabbit), to a large animal model (pig) that more closely mimics human immune response.  Large-scale computer models that capture the interplay between M.tb and its victim will then be used to bring together and analyze a broad range of experimental measurements with the objective of reverse engineering the mechanisms that drive the spread of infection from the lung to other organs and the transmission to other hosts.