‘My main research focus is about discovering the human genes that influence tuberculosis (TB) and I use the diverse genetic ancestry of South Africans to find new genes and pathways involved in the disease. I bring an African perspective to the field of genetics, especially as it relates to human diseases, but have also become involved in population genetics studies.’ Prof Marlo Möller is a professor in the Division of Molecular Biology and Human Genetics, Stellenbosch University (SU) which houses the South African Medical Research Council (SAMRC) Centre for Tuberculosis (TB) Research. She is also an Associate Member of the Centre for Bioinformatics & Computational Biology at SU.
Prof Möller is co-author of a recent article published by Nature magazine. ‘It is about testing models of how humans evolved in Africa. We used genetic data collected from contemporary populations around the world to show that models that were previous suggested were not likely to be correct. We instead proposed a new model – represented by a tangled vine with offshoots – in which stem populations separated but continually exchanged genetic material.’ She adds: ‘Without the diverse genetic data from Africa, this work would not have been possible. I think most scientists dream of publishing in Nature – I always joke that I will retire once a Nature article with me as last author is published – so this publication is definitely a highlight of my career to date!’
Work on TB
She has combined her main strength – being to provide a uniquely African emphasis on the current highly computational field of genetics as it impacts human disease – with her insights into the latest genetic analyses available to the work on genetic susceptibility to TB.
‘Not all individuals who are exposed to Mycobacterium tuberculosis, the bacterium that cause TB, will get infected with it. Further, not all people who get infected with Mycobacterium tuberculosis will get active TB.’
Importantly, she points out, at the moment there is no effective vaccine against TB for adults although new candidate vaccines are being tested. ‘BCG, the only vaccine against TB, is effective mainly in children. We are, however, able to provide effective prophylaxis in the form of the antibiotic Isoniazid, to individuals who are at risk of developing TB after being exposed. This includes individuals living with HIV and others with diseases such as diabetes that suppress the immune system. In countries with a low TB incidence, it is a common practice to give Isoniazid to those that have been in contact with people with active TB. If we are able to identify the genetic variants that predispose individuals to getting active TB, we could prioritise them for prophylactic treatment with Isoniazid. This would help to prevent the spread of disease and could help to eradicate the infection completely.’
Prof Möller stresses that, ‘if we were able to identify why some individuals never get infected with Mycobacterium tuberculosis, even after being exposed at high levels and multiple times, and why some others never develop active TB after getting infected, we could find new ways to prevent people from getting sick.’
She provides another example of the practical application of their work: ‘We are part of PIDDGEN – a collaboration between clinicians, genetic counsellors, immunologists and geneticists that aims to profile the genetic causes of primary immunodeficiencies in South Africans, with a particular focus on the predisposition to TB. We have identified several novel PID-causing mutations in South Africans using state-of-the-art sequencing technologies and these have led to stem cell transplants in specific cases, which are in essence curative.’
In the interest of scientific progress, Prof Möller stresses the importance of interdisciplinary collaboration: ‘It is more than important, it is essential! Much of our work in TB genetic susceptibility spans disciplines and required the input from scientists with diverse backgrounds to progress… I think that organisations such as NITheCS that bridge fields are important to bring researchers from different backgrounds together to explore new research avenues.’
Mentors and influencers
Prof Möller says she loves being a scientist, ‘as we make exciting findings all the time, but it also means seeing the field progress in small increments. I also enjoy working with postgraduate students and seeing them become fully-fledged researchers.’
‘My love for science and computers originates from my father, a primary school science teacher who introduced me to both at a very young age. TB first caught my attention because my high school Biology teacher had contracted this contagious disease. As I am interested in genetics and genealogy, I also traced my family history and discovered that my great-great-grandmother passed away from TB at the age of 33. That brought my research focus that much closer to home.’
Prof Möller mentions some of her important role models: ‘I have been privileged enough to have many influencers and supporters. Prof. Louise Warnich, who just retired as the Dean of Science, was my third-year Genetics lecturer and remains a role model. My PhD supervisor, Prof Eileen Hoal, who is well-established the field of TB genetic susceptibility in South Africa, is still a mentor. Prof. Paul van Helden convinced me that I would be able to complete a PhD, supported me as my PhD co-supervisor and throughout my career, and continues to mentor me. I also have to mention Prof. Jimmy Volmink, our former Dean.’
She adds: ‘As postgraduate student I was lucky enough to have exceptional female scientists such as Profs Valerie Corfield, Hanlie Moolman-Smook and Ms Glenda Durrheim as examples.’
Where research is heading
Asked about current focus and future direction, Prof. Moller responds that ‘both internationally and in South Africa there is an increasing emphasis on understanding how human genetic factors interact with Mycobacterium tuberculosis, both during infection and progression to active disease. We are also heading to precision medicine approaches, where we will be able to use genetic data to personalise TB treatment. Our field is heading beyond the genome: in other words, we are attempting to learn how we can influence our own DNA through health and lifestyle choices. The field is also starting to focus on diverse populations, including those with different genetic ancestries. This diversity provides a rich dataset to identify population-specific genetic risk factors.’
She says it is important to ensure that enough people choose to study and qualify as researchers. ‘We need more role models, mentoring and investment in science. It was interesting to see how the COVID-19 pandemic changed how the world viewed scientists and specifically how articles on clinicians and scientists suddenly replaced those about celebrities and sports.’
Prof Moller adds some important advice: ‘The best reason to consider a STEM career is if it is your passion, because it will help to keep you going even when things are not progressing as you envisioned. Very few people have a straight career trajectory, so don’t get despondent when things aren’t going as planned!’