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TB research professor awarded Oppenheimer Fellowship

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Africa’s premier research fellowship has been awarded to Professor Val Mizrahi, director of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town (UCT). The award recognises Mizrahi as a pre-eminent scholar who has made an internationally significant contribution to the field of microbiology and tuberculosis (TB) research. This is the 21st time that the Harry Oppenheimer Research Fellowship has been awarded, and Mizrahi is the ninth person at UCT to be honoured, writes UCT News.

In 1991, Mizrahi was shortlisted for a Wellcome Trust research scheme. As a young, up-and-coming researcher who had only been working in the field of TB research for a few years, she jumped at the opportunity to fly to London for the interview, despite being eight months pregnant. “I was overly confident,” she remembers. “I walked into that interview and I was completely savaged. My ideas were good but my research proposal was not up to scratch.”

Instead of becoming disheartened she got motivated instead. Almost 30 years later, not only is she a principal investigator and former basic sciences platform lead in UCT’s Wellcome Centre for Infectious Disease Research in Africa but she is also a member of Wellcome’s science interview panel.

In the intervening years, Mizrahi has published 142 peer-reviewed journal articles, supervised or co-supervised 65 postgraduate students and postdoctoral fellows and co-edited the definitive textbook on the biology of Mycobacterium tuberculosis, the bacterium that causes TB. In 2009, she was awarded an A rating from the National Research Foundation, and she currently has an A1 rating. Above all else, she has made a global impact on fundamental TB research. Her research group has investigated the physiology and metabolism of M. tuberculosis, of relevance to TB drug discovery, drug resistance and mycobacterial persistence.

“It was becoming clear that TB was going to become a much more serious problem in South Africa as a result of co-infection with HIV. I was quite fearless and just decided I wanted to work in TB.” It is for these outstanding achievements that she has been recognised with the Harry Oppenheimer Fellowship. The fellowship, which includes R1.5m in funding, will enable her to continue her research in TB drug development in the form of two new research projects.

Mizrahi started her career as a chemist, not a microbiologist. After graduating with a PhD in chemistry from UCT in 1983 she travelled to the US where she completed a postdoctoral fellowship in enzymology at Penn State University and worked on drug discovery for HIV/Aids at SmithKline and French Pharmaceuticals.

She returned to South Africa five years later to establish the Molecular Biology Unit at the South African Institute for Medical Research. It was here that she first decided she wanted to get into TB research. “At the time, I wouldn’t have known a mycobacterium if it jumped out of the petri dish and bit me on the nose,” she remembers.

But this was 1993, the same year the World Health Organisation declared TB a global health emergency. “At the time, it was becoming clear that TB was going to become a much more serious problem in South Africa as a result of co-infection with HIV. I was quite fearless and just decided I wanted to work in TB. Mizrahi also believes that building relationships with collaborators around the world played a key role in helping her to build a world-class research programme in fundamental TB research in South Africa. “It was also clear from developments happening in the rest of the world that this beast of a bacterium might yield to biological investigation through exciting advances in genetics.”

Most scholars can point to watershed moments in their careers. For Mizrahi, the year 2000 was pivotal. “A lot of things coalesced at that time. In 1999, I applied for an SAMRC unit and was awarded it in 2000.” That year also marked Mizrahi’s selection as an international research scholar at the Howard Hughes Medical Institute: she was one of only two from Africa.

“I was able to appoint well-trained microbiologists as postdocs – Sue Anderson and Bhavna Gordhan, who shared a background in bacterial genetics. From very early on, we were involved in genetics and the creation of mutants. Once we had proven our ability, we got the funding to build the first biosafety level 3 lab at the National Health Laboratory Service in Braamfontein, and then a second and a third. “By that time, we had built a sizable research programme.”

Mizrahi remembers this as a very productive and happy time in her career. “We had the freedom to pursue pioneering work and the funding from the SAMRC and other sources meant that I got to recruit superb staff and students, some of whom – Helena Boshoff, Bavesh Kana and Digby Warner – have gone on to become leaders in the TB field.” Mizrahi also believes that building relationships with collaborators around the world played a key role in helping her to build a world-class research programme in fundamental TB research in South Africa.

“Over the years I have been fortunate to collaborate with scientists like Cliff Barry at the National Institutes of Health, Harvey Rubin at Penn and Stewart Cole who is now director of the Institut Pasteur. These scientists were all huge enablers of my work and incredibly generous with their ideas and expertise.”

In 2010, Mizrahi took up the position as director of one of the continent’s largest trans-faculty research institutes: the UCT Institute of Infectious Disease and Molecular Medicine. “I came to this role as a basic scientist, not a clinician, so it was a huge learning curve for me,” she says. “But being the director of an institute with such grand and truly multidisciplinary scope has been enormously satisfying.”

Over the past decade, Mizrahi’s research has all come in a full circle: she is once again working in the field of drug discovery. “I became very passionate about the imperative to make better tools to accelerate drug discovery for TB.” Mizrahi explains that drug development requires a multidisciplinary approach that combines three elements: biology, chemistry and pharmacology. “The biological element has to come from the academic sphere. In South Africa, we have always been able to do clinical trials but we have been less involved in the underpinning basic science, which drives the development of new tools.

“I came to this role as a basic scientist, not a clinician, so it was a huge learning curve for me. But being the director of an institute with such grand and truly multidisciplinary scope has been enormously satisfying.” “What’s very humbling to me as a basic scientist is the necessity but insufficiency of science in tackling this disease which preys on social ills. You can’t develop tools to deal with TB without thinking about the role of poverty.”

Mizrahi proposed two projects as part of the Oppenheimer fellowship. The first, involving collaboration with Professor Digby Warner and Dr Melissa Chengalroyen, is aimed at exploring the many roles of the essential vitamin B2 (riboflavin) in the biology of the TB bacterium. The second builds on a study led by UCT postdoctoral fellow Mandy Mason and will test a longstanding hypothesis of Mizrahi’s regarding the possibility of shortening treatment for TB.

“I’m excited about how the Oppenheimer Fellowship will support this research and the development of new researchers,” says Mizrahi. “Just as my work has been enabled by others, so I too hope to continue to enable younger researchers.

“In a very real sense, I am nothing without the people who have worked with me. The Oppenheimer Fellowship is not mine. I have had fantastic people who have dedicated years of their lives to this type of work. This award is as much theirs as it is mine because that is how science works.”

Although drug-resistant TB only makes up about 5% of the 10m new cases worldwide annually, its burden and cost to society is disproportionately high, Mizrahi is quoted in a City Press report as saying. This is the driver behind her research into new therapies. “However, we need a combination of new tools for controlling the disease – such as vaccines, biomarkers for diagnostics and new drugs,” she says.

The advent of HIV worsened the TB epidemic considerably. Between 50% and 70% of all TB cases in South Africa occur in people who are also infected with HIV. “TB is the leading opportunistic infection associated with HIV. With the widespread roll-out of antiretroviral therapy, we have begun to turn the tide and are seeing a slow decline in the incidence of TB.

“We now have two new antibiotics that are showing great promise for the management of drug-resistant TB. But we need to do more, which will require adequate resourcing,” she says.

Mizrahi is quoted in the report as saying that TB research is underfunded when measured against the number of people who contract TB and the many lives lost because of the disease.

Mizrahi emphasises the challenges involved in TB research: “We need a vaccine – it would be transformative if we could prevent people (from) getting this disease. There are also major diagnostic challenges. We really have a poor understanding of the whole TB transmission process,” she says. “It is a major research focus for people working in this institute.”

University of Cape Town material

City Press report

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