University of Cape Town (IDM)

Institute of Infectious Disease and Molecular Medicine (IDM)

Molecular Mycobacteriology Research Unit

Centre of Excellence for Biomedical TB Research

Member since 2020

Representative

Valerie Mizrahi PhD, Professor Emerita, former IDM Director

Team

• Digby Warner, PhD., IDM Director
• Melissa Chengalroyen, PhD, Senior Research Officer
• Atica Moosa, PhD, Research Officer
• Tim de Wet, MBBCh PhD, Postdoctoral fellow
• Mandisa Zuma, MSc, BSLIII Lab technician

About

The Institute of Infectious Disease and Molecular Medicine (IDM) supports discovery and clinical research, translation, and early-career development focused on diseases relevant to Africa. As the largest cross-faculty institute at the University of Cape Town (UCT), the IDM comprises five buildings on UCT’s Health Sciences campus and extends across clinical research sites in Cape Town, and the entire Western Cape province. Incorporating advanced laboratories and analytical technologies, comprehensive clinical trial capacity, embedded community partnerships, and computational and support infrastructure, the IDM’s vision is for Africa-led discoveries and interventions to contribute to a healthier world. IDM researchers collaborate widely, and the Institute is regularly cited among the UCT’s flagship entities for its contributions to research and training outputs. Research conducted in the IDM has been especially influential in the prevention and management of HIV and HIV-associated infections, the diagnosis, immunopathogenesis, and management of TB, and the discovery and evaluation of new TB biomarkers and vaccines. As high-priority focus area, TB research in the IDM spans the full discovery and development pipeline, including mycobacterial physiology and metabolism, host-pathogen interactions, drug target identification and validation, biomarker discovery, translational immunology, preclinical drug evaluation, and clinical studies of therapeutics, biomarkers, and vaccines.
Valerie Mizrahi and Digby Warner participate in the TBDA through the Molecular Mycobacteriology Research Unit (MMRU), a UCT-accredited unit they lead within the IDM. Their group focuses on studying aspects of the physiology and metabolism of M. tuberculosis relevant to TB drug discovery, drug resistance, and the aerobiology of TB transmission. As TB biologists, they and their team contribute to the TBDA by biologically profiling and elucidating the mechanisms of action of novel antimycobacterial agents. They have specialist expertise in mycobacterial genetics, chemical biology, and the application of single cell approaches in TB research (imaging, flow cytometry).

Links

Valerie Mizrahi, Tackling big questions in tuberculosis: a TB biologist’s view from South Africa. Science talk presented at the Life Sciences Across the Globe Seminar series, August 5, 2020 (virtual)

Valerie Mizrahi, Planning for research impact: lessons from a decade as director of the IDM. Wolfson Memorial Lecture, University of Cape Town, November 22, 2021 (hybrid)

References

1. Abrahams, G. L.; Kumar, A.; Savvi, S.; Hung, A. W.; Wen, S.; Abell, C.; Barry, C. E.; Sherman, D. R.; Boshoff, H. I. M.; Mizrahi, V. Pathway-Selective Sensitization of Mycobacterium Tuberculosis for Target-Based Whole-Cell Screening. Chemistry & Biology 2012, 19 (7), 844–854. https://doi.org/10.1016/j.chembiol.2012.05.020.
2. Evans, J. C.; Trujillo, C.; Wang, Z.; Eoh, H.; Ehrt, S.; Schnappinger, D.; Boshoff, H. I. M.; Rhee, K. Y.; Barry, C. E.; Mizrahi, V. Validation of CoaBC as a Bactericidal Target in the Coenzyme A Pathway of Mycobacterium Tuberculosis. ACS Infectious Diseases 2016, 2 (12), 958–968. https://doi.org/10.1021/ACSINFECDIS.6B00150.
3. Naran, K.; Moosa, A.; Barry, C. E.; Boshoff, H. I. M.; Mizrahi, V.; Warner, D. F. Bioluminescent Reporters for Rapid Mechanism of Action Assessment in Tuberculosis Drug Discovery. Antimicrobial Agents and Chemotherapy 2016, 60 (11). https://doi.org/10.1128/AAC.01178-16.
4. Moosa, A.; Lamprecht, D. A.; Arora, K.; Barry, C. E.; Boshoff, H. I. M.; Ioerger, T. R.; Steyn, A. J. C.; Mizrahi, V.; Warner, D. F. Susceptibility of Mycobacterium Tuberculosis Cytochrome Bd Oxidase Mutants to Compounds Targeting the Terminal Respiratory Oxidase, Cytochrome c. Antimicrobial Agents and Chemotherapy 2017, 61 (10). https://doi.org/10.1128/AAC.01338-17.
5. de Wet, T. J.; Winkler, K. R.; Mhlanga, M.; Mizrahi, V.; Warner, D. F. Arrayed Crispri and Quantitative Imaging Describe the Morphotypic Landscape of Essential Mycobacterial Genes. eLife 2020, 9. https://doi.org/10.7554/eLife.60083.
6. Chengalroyen, M. D.; Jordaan, A.; Seldon, R.; Ioerger, T.; Franzblau, S. G.; Nasr, M.; Warner, D. F.; Mizrahi, V. Biological Profiling Enables Rapid Mechanistic Classification of Phenotypic Screening Hits and Identification of KatG Activation-Dependent Pyridine Carboxamide Prodrugs With Activity Against Mycobacterium Tuberculosis. Frontiers in Cellular and Infection Microbiology 2020, 10. https://doi.org/10.3389/fcimb.2020.582416.
7. Evans, J. C.; Murugesan, D.; Post, J. M.; Mendes, V.; Wang, Z.; Nahiyaan, N.; Lynch, S. L.; Thompson, S.; Green, S. R.; Ray, P. C.; Hess, J.; Spry, C.; Coyne, A. G.; Abell, C.; Boshoff, H. I. M.; Wyatt, P. G.; Rhee, K. Y.; Blundell, T. L.; Barry, C. E.; Mizrahi, V. Targeting Mycobacterium Tuberculosis CoaBC through Chemical Inhibition of 4′-Phosphopantothenoyl- l -Cysteine Synthetase (CoaB) Activity. ACS Infectious Diseases 2021, 7 (6), 1666–1679. https://doi.org/10.1021/ACSINFECDIS.0C00904.
8. Chengalroyen, M. D.; Mason, M. K.; Borsellini, A.; Tassoni, R.; Abrahams, G. L.; Lynch, S.; Ahn, Y.-M.; Ambler, J.; Young, K.; Crowley, B. M.; Olsen, D. B.; Warner, D. F.; Barry, C. E.; Boshoff, H. I. M.; Lamers, M. H.; Mizrahi, V. DNA-Dependent Binding of Nargenicin to DnaE1 Inhibits Replication in Mycobacterium Tuberculosis. bioRxiv 2021, 2021.10.27.466036. https://doi.org/10.1101/2021.10.27.466036.