Dr Valerie Mizrahi, Professorial Director of the Institute of Infectious Disease and Molecular Medicine (IDM), is an outstanding researcher in the basic science of tuberculosis in Africa and widely recognised as an international leader in the field. She is a member of the TB Programme Scientific Advisory Committee of the Bill and Melinda Gates Foundation and was interim Chair of its ‘Discovery Expert Group’ in 2017. She is also a member of the Science Interview Panel of the Wellcome Trust, and a member of the Scientific Advisory Board of the ‘TB Human Challenge Model Consortium’, Harvard School of Public Health.
Mizrahi obtained her PhD in Chemistry at the University of Cape Town and pursued her early research interests and specialist training in enzymology and drug discovery for HIV/AIDS in the USA. After returning to South Africa in 1989, she established the Molecular Biology Unit at the South African Institute for Medical Research and moved into the field of TB research in 1993, the year that the World Health Organisation declared TB a “global health emergency”. Professor Mizrahi enjoyed a successful twenty-one year career at the University of the Witwatersrand and National Health Laboratory Service in Johannesburg and moved to UCT to lead the IDM in 2011. She has held a NRF A-rating since 2009 and is a member of the Academy of Science of South Africa as well as a Fellow of the African Academy of Sciences, the American Academy of Microbiology, Royal Society of South Africa and The World Academy of Sciences. The winner of numerous awards and prizes – the SA Medical Research Council’s Platinum Achievement Award (2017), the Prix Christophe Merieux (2013), Order of Mapungubwe (Silver, 2007), the SA Society for Biochemistry & Molecular Biology Gold Medal (2006), Department of Science & Technology Distinguished Women Scientist Award (2006) and the UNESCO-L’Oreal Prize for Women in Science, Africa and Middle East Region (2000) – amongst others, Valerie has published over 140 peer-reviewed original research articles and book chapters in the areas of organic chemistry, enzymology, biochemistry and mycobacterial physiology and metabolism. In 2017, she co-edited the definitive textbook on the biology of Mycobacterium tuberculosis. She has (co)-supervised more than 65 postdocs and graduate students, some of whom have moved into leadership positions in TB research locally and abroad.
The field of TB research is desperately in need of innovative approaches, since the questions of how the pathogen can remain latent for so many years, and how it maintains its genetic integrity yet develops resistance to drugs so readily, remain mostly unanswered. Tuberculosis is now the largest cause of death in the world from any infectious disease and imposes a particular burden on South Africa. With co-infection with HIV and increasing emergence of multidrug resistance, TB has thwarted current strategies to control it. It has become clear that adequate modern tools for diagnosis, prognosis and treatment are lacking, largely because we still have such a limited understanding of the pathogen, M. tuberculosis, and the host responses to it. Professor Mizrahi has been one of the pioneers of applying modern molecular biological technologies to understanding the requirements for growth and pathogenesis of the tubercle bacillus.
Professor Mizrahi plans to use the Oppenheimer Fellowship to develop two new areas of research which are built on her group’s expertise in the biology of Mycobacterium tuberculosis as it relates to TB pathogenesis and drug discovery. The first study aims to use state-of-the-art genetic tools to modulate the TB bacterium’s pathway for its own production of an essential vitamin, riboflavin, and in so doing, to modulate a component of the host immune response to M. tuberculosis infection, which appears to be partly driven by recognition of chemical intermediates in the riboflavin biosynthesis pathway. The second study is aimed at addressing one of the biggest challenges in TB drug discovery, namely, how to achieve dramatic treatment-shortening. This study will use a chemical-genetic approach to identify and target bacillary factors that negatively affect the efficacy of existing TB drugs, with a view to accelerating the rate at which M. tuberculosis is killed outright by antibiotics. These projects will also serve as the vehicle for advanced training of talented, next-generation TB researchers who are able to work at an internationally competitive pace and standard.