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Mycobacterium tuberculosis (MTB), the etiological agent of tuberculosis and one of the most successful human pathogens, caused 8.6 million incident cases of tuberculosis (TB) and claimed 1.3 million lives in 2012, in spite of century-long efforts to combat it. New drugs, vaccines and diagnostic tests for TB are clearly needed, but their development is hampered by poor understanding of the basic biology of this pathogen. Global studies on MTB at the systems level rather than traditional one gene or one protein approaches should lead to breakthroughs, however, new tools with which to investigate the basic biology of MTB and its interactions with the host at the systems level are urgently needed.
To address this problem, we have just constructed a functional MTB proteome microarray covering 95% of the proteome, and a complete ORFome library (Cell reports, 2014). We demonstrate the broad applicability of the microarray by investigating global protein-protein interactions, small molecule-protein binding, and serum biomarker discovery, identifying 59 PknG-interacting proteins, 30 c-di-GMP binding proteins, and 14 MTB proteins that together differentiate between TB patients with active disease and recovered individuals. Results suggest that the MTB rhamnose pathway is likely regulated by both the serine/threonine kinase PknG and c-di-GMP. This new resource has potential to generate greater understanding of key biological processes in the pathogenesis of tuberculosis, possibly leading to new therapies for the treatment of this ancient disease.
Based on this powerful platform, we are now trying to tackle Mtb on a systems level. Several systems biology projects are now ongoing in our laboratory, e.g., global host-pathogen protein-protein interaction, phosphorylation network, pupylation regulation network, drug mechanism, as well as serum biomarker identification.
Tao Lab, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong UniversityPowered by WEBBER SOFTWARE ©2008-2014 www.chinawebber.com