“Our collaboration with the GCRF START grant has allowed us to gain new skills and experience that has fast-tracked our research programme in antimicrobial drug discovery. It played an integral part in Blake’s development as a scientist too, through the visits to the UK’s national synchrotron, Diamond Light Source and XChem, and this investment is already paying forward as new students are being trained.”Professor Erick Strauss, Strauss Laboratory, Stellenbosch University, South Africa
My name is Blake Howard Balcomb, and I am a Post-doctoral Research Fellow funded by the GCRF START grant in the Department of Biochemistry at Stellenbosch University in South Africa. My research degrees, throughout the years, have centered on tackling the global and local challenges of human health and disease, motivated by my experiences growing up on a small farm in rural KwaZulu-Natal, South Africa. During those times and since, I have seen the stark impact that health epidemics such as HIV/AIDS and Tuberculosis (TB) have on society, as well as the effects on family livelihoods. And so, from a young age, it was only natural that I had a strong inclination to try and help my local communities where I could. Originally, I had an interest to pursue a medical degree; however, after seeing the wonderful world of microorganisms under a microscope I was set on a science career. I was also very fortunate to have several terrific mentors and supervisors during all my research degrees that have played a big role in the scientist I am today, enabling me to share my experience with my colleagues.
For me, the beauty of science and research is that one can ask difficult questions and sometimes come across new unexpected answers or perspectives. I relish the idea that a basic scientific discovery has the potential to lead onto bigger things that could contribute towards combating a debilitating disease. This is where the GCRF START grant has provided me with some important opportunities: from learning new skills through training and mentoring, to participating in new international collaborations and building on the experience of my early post-graduate studies. These skills I have been able to pass on to my peers and so contribute to capacity building efforts here in Africa.
During my Master’s degree (2011-2014), before GCRF START came into being, I got my first taste of international collaboration whilst on a Fulbright scholarship in the USA, working with talented enzymologist, Prof Audrey Lamb. In the Lamb laboratory I was introduced to the wonderful world of protein X-ray crystallography. This technique allows one to use powerful scientific instruments to bombard the sample of interest with X-rays and compile a zoomed-in three-dimensional picture (more than ~1,000,000 times the zoom power of a regular laboratory microscope) of a protein and gain insight into its structure, which is important in understanding the chemical reactions that it might entail. These details can help one understand some of the broader biological complexities that occur in healthy, as well as diseased cells. I think in many ways this was a major eye-opener as to the multiple opportunities that one has access to, if one takes the time and effort to make contact with a leading expert in the field, and it can certainly open many doors. And this for me was a great parallel to South Africa in that although we are a developing country, we have an immense pool of talented young scientists that I am confident will solve many of the global health pandemics and challenges we face in society today – from drug resistance, HIV vaccines and Tuberculosis (TB), to anti-malarial drugs and even cancers.
Following the completion of my PhD in 2019, at Stellenbosch University in the Department of Biochemistry, I was introduced to the GCRF START grant through my supervisor, Prof Erick Strauss, who is a GCRF START Co-I and the Group Leader of the Strauss Laboratory. This has certainly been one of my highlights in my research career, not only as a highlight for the cutting-edge science capabilities I experienced first-hand when I visited Diamond Light Source (Diamond) in the UK, but equally importantly, for the genuine interest, support, and encouragement that the GCRF START team provides. Many of the beamline scientists at Diamond have freely shared their scientific expertise and hands-on experience in assisting me to get the most out of the experiments that I conducted at Diamond, and I am enjoying passing these skills on to other researchers here in South Africa.
The Strauss Laboratory primarily relies on outsourcing many of the structural biology related aspects of the projects that we work on. Therefore, through the GCRF START grant, it has been very gratifying using the training that I received during my Master’s degree on my Fulbright scholarship in the USA together with the new skills I am gaining as a START Post-doc, to help develop our own structural biology capabilities within our department at Stellenbosch University. This, of course, has led to multiple opportunities for training the next generation of structural biologists, as well as opening the opportunity to collaborate with colleagues within our department and hopefully in the future, colleagues across the African continent. Being one of the more senior researchers in the Strauss Laboratory I have had the opportunity to train several junior and senior members in our laboratory such as Master’s student, Karli Bothma, in our research group.
Being formally trained in structural biology, I have also been able to assist and team up with another GCRF START PDRA, Dr Anton Hamann. Anton originally trained as an organic chemist (now retrained in the art of protein X-ray crystallography), and so it has been very rewarding training and learning together with a fellow colleague funded by GCRF START. It is these networking connections with other researchers that often lead to career-long collaborations.
The GCRF START grant has allowed us to initiate exciting new collaborations on my projects, as well as visit and use Diamond Light Source for the first time. Through Diamond’s X-ray structure-accelerated, synthesis-aligned fragment medicinal chemistry (XChem) facility, under guidance from GCRF START Co-I, Prof Frank von Delft, we have been able to fast track the identification of novel compounds that we are currently pursuing further as promising antimicrobials against Staphylococcus aureus. In South Africa, more than 50% of bacterial infections isolated in hospital settings are S. aureus strains. S. aureus infections range from mild to life threatening, and the bacteria are notoriously known for their resistance against many of the first-line antibiotics.
The GCRF START grant has in addition enabled us to initiate another new collaboration with Dr Nir London at the Weizmann Institute of Science to develop compounds that target this protein covalently (form an irreversible attachment to proteins). This approach is also based on a high-throughput setup that screens several fragments which contain specific reactive groups. The results of the most reactive fragments are then again fed back into the XChem workflow, whereby one would be able to visualise the compound – protein complex. All these findings help aid the development of potent and specific compounds that could be assessed further in the drug discovery pipeline, and in turn, the discovery of novel antimicrobials to tackle disease challenges both here in Africa and beyond.
It is indeed very exciting — as an African scientist — to have the opportunity to receive training on these cutting-edge techniques, not only in the pursuit of identifying promising antimicrobial compounds but also from a capacity skills development aspect. Learning these particular techniques is very valuable in that it allows me to train and impart the knowledge I have gained to the next generation of scientists in South Africa involved in drug discovery initiatives on the African continent. For example, one of the post-graduate students I passed these new skills to is Nicholas Herbert, who is now an MSc. student at the Africa Health Research Institute (AHRI) in Durban (in KwaZulu-Natal). Nick reports on the impact of this ‘peer-training’ below,
“Being trained on X-ray crystallography has opened my eyes to its very diverse and useful application. Finally seeing the atomic structure of our protein, after the riveting experience of collecting data remotely from our laboratories in South Africa, was an incredibly rewarding experience and I am grateful to have been taught such a technique by Dr Balcomb. I will eagerly be looking for the next opportunity to gain further experience in X-ray crystallography.”
We are thrilled too that – through the GCRF START Grant – these new collaborations and preliminary data have allowed us to submit a grant application (2nd Drug Discovery Call – Grand Challenges Africa Round 10). This program is a partnership between the African Academy of Sciences (AAS), the Bill & Melinda Gates Foundation (BMGF), Medicines for Malaria Venture (MMV), and the University of Cape Town (UCT) Drug Discovery and Development Centre (H3D)) – so watch this space!
Commenting on the impact over the course of the collaboration with the GCRF START grant, Professor Erick Strauss, Group Leader at Stellenbosch University’s Strauss Laboratory, said,
“We are extremely thankful for the opportunities we’ve already had as part of the GCRF START grant and are looking forward to what it will unlock in the future.”
Read about the UN’s Sustainable Development Goals for Health and Wellbeing here.
 Int J Infect Dis. 2018 Aug; 73:78-84. doi: 10.1016/j.ijid.2018.06.004