The CBTBR was established in July 2004 and signifies the governments commitment in finding solutions to one of the continents most threatening diseases.
The SU Node of the CoEis housed within the Division of Molecular Biology and Human Genetics at Stellenbosch University (SU), which also hosts the SAMRC Centre for Tuberculosis Research. The research conducted within the SU node spans basic to translational and clinical research, largely focused on Tuberculosis (TB) and on the quality training of students. Various research teams form this node, each with its own research niche.
The research conducted in the laboratories of the CBTBR is internationally recognized. The two nodes of the CBTBR are positioned adjacently on the research continuum. The University of the Witwatersrand (Wits) node of the CBTBR is at the forefront of fundamental research in mycobacterial metabolism that is aimed at identifying, validating and characterizing novel drug targets and vaccine candidates for TB. The major areas of interest in this laboratory include the molecular mechanisms underlying the regulation of dormancy and persistence in M. tuberculosis and the mechanisms of DNA metabolism underlying the development of strain diversification and the evolution of drug resistance. These areas are being investigated using a highly inter-disciplinary approach involving molecular genetics, biochemistry, microbial physiology, bioinformatics, comparative genomics and transcriptomics.
The research program of the UCT node comprises a highly integrated suite of 12 projects that are aimed at investigating aspects of the physiology and metabolism of M. tuberculosis of relevance to TB drug discovery, TB drug efficacy, mycobacterial persistence and TB transmission. The research program falls under three broad thematic areas: mycobacterial metabolism and physiology; TB drug discovery; and TB transmission. Projects 1-7 are built on areas of fundamental mycobacterial metabolism and physiology research; this thematic area has grown considerably over the past year with some exciting new projects having been initiated that take advantage of new developments in high-throughput genetic technologies for mycobacteria (Tn-Seq and CRISPRi) coupled with the establishment of advanced imaging capabilities in our and other laboratories in the Institute of Infectious Disease and Molecular Medicine at UCT (time-lapse fluorescence, confocal and super-resolution microscopy). As outlined below, the projects in this theme are of direct relevance to our work under the themes of TB drug discovery and TB transmission. Thus, projects 8 and 9 are based on the application of our capabilities in mycobacterial genetics and physiology in the area of drug discovery. Project 8 comprises 7 sub-projects, whereas Project 9 represents a new area of investigation for the UCT node at the host-pathogen interface. Projects 10-12 represent another major growth area for the UCT node focused on the topic of TB transmission. These projects form part of larger interdisciplinary studies on the aerobiology and genomics of TB transmission, funded by UCT’s Flagship 1 grant from the SAMRC and a grant from the Bill and Melinda Gates Foundation (BMGF).
Research at the Wits node covers identification and validation of novel drug targets for TB, with a particular focus on peptidoglycan, DNA repair and mycobacterial oxidative phosphorylation as tractable areas for the discovery of new drugs. Enzymes that remodel the peptidoglycan are essential for bacterial cell division and the Wits node has uncovered a novel class of amidases that are essential for bacterial survival. In addition to this, the Wits node is also focused on investigation of microbial heterogeneity in TB diseased individuals, prior to the initiation of treatment and during treatment. In this regard, they have described the prevalence of differentially culturable tubercle bacteria (DCTB) in the sputum of treatment naïve individuals and in the process of studying how the prevalence of these organisms changes during treatment. In addition, the Wits node supports the rollout of molecular TB diagnostics in South African and almost 20 other countries through the provision verification and quality assurance reagents. Finally, researchers at the Wits node have been involved in the search for new TB drugs through screening of compounds/extracts from medicinal plants. Research highlights in these four thematic areas are detailed in the "Overview and Highlights of Progress report".