“It is fascinating! I believe the GCRF START grant has laid a strong foundation for me to becoming an independent early career Structural Biologist. Now I am hands-on, a biochemist being chaperoned into the world of X-rays, electrons, neutrons, quantum mechanics and GPUs”
Dr Stanley Makumire, GCRF START Postdoctoral Research Fellow, University of Cape Town, South Africa.
My name is Stanley Makumire. I was born in Zimbabwe and have had a passion for Maths and Science for as long as I can remember. My desire is to gain an understanding of how disease works at the atomic level and thereby address important Sustainable Development Goals for health and wellbeing (SDG3). I had not encountered structural biology until I attended the Biophysics and Structural Biology at Synchrotrons workshop in Cape Town in early 2019 (17‐24 January), which was jointly funded by the GCRF START grant and the International Union of Pure and Applied Biophysics. At that meeting, I saw the cutting-edge work being done by people in the GCRF START programme and realised that understanding macromolecular structure was the key to understanding biochemistry, and this has inspired my research journey ever since. At the time I was completing my PhD at the University of Venda in the Limpopo province of South Africa, where none of the resources to do such work were available. Therefore, I was determined to collaborate with the GCRF START programme at the University of Cape Town (UCT).
Given the disease burden in Africa, my main career goal is to eliminate or minimise disease progression using molecular and structural biology tools, with proteins as targets using small molecules designed by rational processes as drugs. This knowledge has provided insights used to design medicines and vaccines. I am motivated by the rapid advance of biophysics that we have witnessed in response to the COVID-19 pandemic. This has clearly demonstrated the power of today’s visualisation technology and the field of Structural Biology in vaccine design.
Studying the mechanisms of enzymes of the nitrilase superfamily
I was motivated to join Prof. Bryan Trevor Sewell for my Postdoctoral Fellowship, which I was awarded through the GCRF START grant in 2020. Prof. Sewell is a GCRF START Co-investigator in the Structural Biology Research Unit at the University of Cape Town. I had applied to do postdoctoral studies on the mechanisms of enzymes of the nitrilase superfamily. These ubiquitous enzymes play a variety of roles in cellular processes, and many have found industrial roles in chemical synthesis and environmental protection. However, discovering how they work has been beset with difficulties.
It has been known for some time that three different amino acids play a pivotal role in their function: a cysteine, two glutamates and a lysine. Excellent clues have come from X-ray crystallographic studies (Fig.1), but the literature contains a multitude of different interpretations of the available evidence. The problem is that X-rays cause the cysteine to become oxidized and cannot image hydrogens (which are a key players) and electrons destroy the glutamates so that they are invisible in images obtained by electron microscopy. The tricks to circumvent these problems used by various investigators have introduced artifacts of their own and therefore a definitive mechanism has eluded humanity.
Overcoming the challenges with neutrons
Neutrons are known to be the least damaging of all atomic resolution imaging probes and furthermore, they enable the imaging of hydrogens (in fact, deuterium that has exchanged with the natural hydrogen). But imaging by neutron crystallography is also beset by difficulties, including the fact that the crystals required must be enormous making it necessary to prepare vast quantities of protein. To add to these difficulties, there are only six suitable neutron beams in the world, so access to an appropriate facility is very restricted. I have overcome these difficulties with the help of Zoë Fisher, who is the group Leader of the Deuteration and Macromolecular Crystallization (DEMAX) platform at the European Spallation Source, and Mathew Blakeley, instrument scientist at the Quasi-Laue diffractometer (LADI-III) at the Institut Laue-Langevin (ILL). I am in the process of collecting data and learning of the remarkable insights that can be obtained by using neutrons to study the enzyme mechanism. Determining a neutron structure of this amidase will form the basis of proposing a novel mechanism and I am excited since the preliminary results are very promising. This would be a game changer!
Opportunities, resources, and capacity building through the GCRF START grant
“GCRF START has provided me with opportunities and resources that I would never have believed were possible to access from the African continent. Participating in the START grant programme has been an extraordinary experience.”
During the first year of my GCRF START-funded Fellowship, I was able to collect, process and interpret X-ray data, process and interpret high resolution cryoEM data collected at the world-class Electron Bio-Imaging Centre (eBIC) at the UK’s national synchotron, Diamond Light Source, thereby solving the structure of the Plasmodium falciparum glutamine synthetase (deposited as EMDB entry ID EMD-12589). I used molecular mechanics software to explore the active site of amidases and interpret quantum mechanical models of the amidase active site, thus adding substantial value to the X-ray structures. I have participated in projects related to anti-malarial drug design and had the opportunity to reinterpret the literature on amidase mechanism.
I have met and interacted with leading scientists through my GCRF START Fellowship who have helped me to achieve my objectives. I have also met other early career scientists involved in START projects and collaborations, and I am amazed at how far they have progressed. I am excited that, because of the GCRF START grant, I am becoming one of the very small cohort of young people in Africa that have the knowledge to contribute to the field of Structural Biology.
Commenting on Stanley’s research progress and his involvement in multiple international collaborations, Prof. Sewell said,
“Stanley has maintained spectacular productivity in spite of the challenges caused by lockdown due to the Covid-19 pandemic. He has engaged with a remarkable array of science and technology at UCT’s Aaron Klug Centre for Imaging and Analysis and has built rapidly on the work of others to bring several projects to fruition. His enthusiasm and passion have been maintained by interaction with the GCRF START team and he has leveraged this network to make contact and collaborate with neutron crystallographers at ILL and DEMAX. This clearly demonstrates the process by which capacity has been built in Africa through the GCRF START grant.”
Find more information about the UN’s Sustainable Development Goals here
My name is Maria Hamunyela, and I am a second year PhD student in the structural biology research group at the University of Pretoria, South Africa. Born and raised in a small town in northern Namibia, I was inspired to pursue my studies in science by women scientists that I have come across. Women in science face extra challenges, having to balance their careers and personal lives. I was raised by strong black women, including my mother, from whom I draw my strength. My parents never had the same opportunities and therefore, on completion of my studies, I will be the first PhD holder in my family.
Although I work for the University of Namibia as a technologist, I chose to continue my studies at the University of Pretoria under the supervision of GCRF START Co-I, Prof Wolf-Dieter Schubert, due to limited research funding and the lack of structural biology facilities in my country. This has provided me with access to world-class equipment, such as the UK’s national synchrotron, Diamond Light Source (Diamond).
The impact of Escherichia coli (ETEC) and related diseases – the scale of the challenge
I am currently investigating the secreted EatA protein of enterotoxigenic Escherichia coli (ETEC) bacteria. ETEC commonly causes watery diarrhoea in children younger than five years old killing many children in this age group. ETEC also causes malnutrition and stunting in children. I decided to work on this project because ETEC affects young children in developing countries in regions with limited access to clean water and sanitation. This is true of many people in both Namibia and South Africa who are correspondingly severely affected by water and food borne pathogens such as ETEC and Shigella.
Globally, ETEC and Shigella are estimated by the World Health Organisation to cause ~400 million episodes of diarrhoea annually in children under five years of age (WHO 2009) causing moderate and severe stunting in ~2.6 and ~2 million children, respectively. Studying ETEC can help to develop vaccines and drugs against ETEC and related diseases.
Studying the functions and structure of the EatA protein passenger domain
The passenger domain of the EatA protein is required for the virulence of ETEC. It degrades Mucin 2, a protective protein secreted by, and covering the intestinal epithelium. Previous reports show that the EatA passenger domain is a potential vaccine candidate for ETEC and other enteric pathogens such as Shigella flexneri. However, the functional and structural properties of the EatA passenger domain have not been extensively studied. The full biological function of EatA passenger domain is therefore not well understood and might support infections in yet other ways. Studying the functions and the structure of EatA passenger domain will provide a better understanding of ETEC pathogenesis.
A first step in studying the EatA passenger domain will be to introduce an affinity tag in the middle of the protein to simplify protein production and purification. This is non-trivial as both the N- and C-terminal ends are not available for the placement of such a tag and inserting it in the wrong place could affect the stability and the function of the protein. Once the protein has been produced and purified, the substrate specificity will be investigated by designing an enzyme activity assay. Observations on the optimal substrate will ideally allow the development of an inhibitor. Identifying other host proteins that interact with the target protein could provide information about additional functions. Structural and biophysical experiments will include thermal unfolding and refolding studies, co-crystallisation and finally X-ray diffraction to provide a fuller understanding of the role of EatA.
The WHO/UNICEF Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) aims to reduce deaths from diarrhoea in children younger than five to less than 1 per 1000 live births by 2025 (WHO/UNICEF, 2013). Hopefully designing an inhibitor for EatA will be a fundamental step in achieving this goal
Collaborating with the GCRF START grant and next steps
It took more than a year of searching for opportunities before I came across Prof Wolf-Dieter Schubert and he accepted me to join his structural biology research group at the University of Pretoria. This is how the GCRF START programme afforded me the opportunity to study towards my PhD studies. The main benefit is that I now have access to Diamond, to world-class synchrotron techniques, and I have the reagents that I need to do my research. I am also getting scientific training, not only in the laboratory but through workshops connected to START. In addition, I am fortunate to be a part of a supportive research group.
As I am employed by the University of Namibia as a technologist, I will return to Windhoek (Namibia) in the future, and hopefully start my own academic research group in structural biology. If interesting opportunities arise, I would love to work for an international research facility or even the public sector. While the scientific industry in Namibia is still in its infancy, I may be able to bring my own knowledge to setting up a new company.
Read more about the UN’s Sustainable Development Goals here
From medicinal chemist to protein crystallographer, Dr Anton Hamann has made remarkable strides in structural biology despite many challenges. These achievements he attributes to new doors of opportunity which have opened as a result of GCRF START grant funding for his role as a Post-doctoral Research Fellow at Stellenbosch University, South Africa – a role which has changed his life and career in many ways. Although possessing “no previous experience” (as he puts it) in the particular techniques and skills required, Anton has not only retrained into a new field of science in a short space of time, but he has also learnt world-class techniques scarce in Africa, and now develops small and novel molecule inhibitors to combat diseases. Here is his inspiring story in his own words….
My love for science and medicine
My name is Anton Hamann and I grew up on the outskirts of Cape Town, in the Western Cape of South Africa. I was diagnosed with severe hearing loss in both ears with no possibility of recovering the loss. Despite this, from a very young age, I enjoyed science and building contraptions. I was also a bookworm and always enjoyed visiting the local library. My high school science teacher was extremely passionate in chemistry and motivated me to pursue a degree in chemistry. As a result, I decided to pursue a career in science, starting with a BSc degree in Chemical Biology at the University of Stellenbosch. After that, I started with my postgraduate studies (BSc Honours, MSc and PhD) with organic chemistry as my discipline.
I was always fascinated in medicine and how it affects our bodies and staves off diseases. It was questions like – What molecules are involved and how do these molecules change the biology in our bodies? How can we use these molecules to combat diseases? Can we cure these diseases with better molecules? What are these molecules? – that intrigued me.
This prompted me to do research in the field of medicinal chemistry which is a multi-functional field with various applications in drug discovery, drug design, synthetic chemistry, and protein molecular modelling. During my MSc and PhD, I focused on developing drugs with better medicinal properties for the treatment of malaria and Alzheimer’s disease. Over the course of time, I have synthesised several molecules that have the potential to be further developed into medicinal drugs for malaria and Alzheimer’s disease. This has resulted in two publications for my work in malaria (South African Journal of Chemistry, 2013, 66, 231-236 and Bioorganic & Medicinal Chemistry Letters, 2014, 24, 5466-5469) and we are currently in the process of publishing the Alzheimer’s disease results in a peer reviewed journal.
Re-training as a protein crystallographer
After my PhD, I decided to carry on with my research in the field of medicinal chemistry but was looking for a new challenge. This is when I joined Prof. Erick Strauss’ research team as a post-doc to explore the possibilities of developing novel antibiotics for Staphylococcus aureus. This is also where I heard about the GCRF START grant for the first time.
Although GCRF START’s life sciences focus is mainly structural biology, a field in which I possessed no previous experience, I was determined to learn as much as possible and be retrained as a protein crystallographer. This is where the START grant made a significant impact on me, not only fully funding my role as a post-doc but also giving me opportunities to attend conferences and workshops in South Africa and UK, and to hone my skills as a protein crystallographer. As I’ve progressed during my post-doc, I have become a better medicinal chemist with the new skills that I have developed in the field of structural biology thanks to the opportunities provided by the GCRF START grant.
The GCRF START grant has given me an incredible opportunity to visit XChem twice for two weeks in total at the UK’s national synchrotron, Diamond Light Source (Diamond), to carry out X-ray crystallographic fragment screening experiments. I’ve gained valuable experiences from Dr Romain Talon and Dr Alice Douangamath and these visits also introduced me to a new field of high-throughput screening where the workflow is almost fully automated. I’ve had access to Diamond’s state-of-the-art equipment including the I04-1 beamline. During this time, I’ve had the opportunity to soak my protein crystals with hundreds of different fragments to identify potential small molecules that bind to the enzyme. These molecules can then be expanded into larger molecules with higher potency and act as antibiotics for Staphylococcus aureus.
To date I’ve used the I03, I04 and I04-1 beamlines at Diamond to obtain diffraction data of my Staphylococcus aureus protein crystals which was extremely valuable to my research. I have also attended a CCP4 (Collaborative Computational Project Number 4) workshop in York in the UK, where I learned how to process the diffraction data to solve the crystal structures. GCRF START is one of the CCP4 workshop partners.
Another benefit of the GCRF START grant has been the fruitful collaborations and relationships that I have built with other South African and British structural biologists who have significantly aided my career progression. In addition, I have learned valuable tips and skills from Romain and Alice at Diamond. They gave me insights on how to achieve optimal crystals and what to do if your proteins do not crystallise. They have been incredible in assisting me with the XChem project.
Commenting on Anton’s achievements and the support of the GCRF START grant, Prof. Erick Strauss said,
“I’ve always personally been of the opinion – and this is especially relevant in the South African context – that a scientist with multiple skill sets and the ability to transition easily between fields is more likely to make a deep impact. It was with this in mind that I was really happy to welcome Anton into my group: as a skilled synthetic chemist I was certain that he would be more than able to take on protein crystallography to bridge the chemistry/biology divide. And without the GCRF START grant, this would not have been possible – we are extremely thankful for this support.”
I would like to thank Prof. Erick Strauss, who is a GCRF START Co-Investigator, for taking a gamble on someone like me who is an organic chemist and not a biochemist! The effort he was willing to put into me and this project is highly appreciated. I couldn’t have asked for a more invested supervisor. I am also grateful to my lab mates, Dr Blake Balcomb (GCRF START-funded Post-doctoral Research Fellow) and Konrad Mostert, for teaching me the nuts and bolts of protein chemistry. I am also thankful to Dr Carmien Tolmie (previously a GCRF START-funded Post-doctoral Research Fellow) and the other GCRF START Co-Investigators, Prof. Trevor Sewell, and Prof. Wolf-Dieter Schubert for their work behind the screen to keep things running smoothly. Lastly, a big thank you to the people at Diamond for making this a reality.
Read about the UN’s Sustainable Development Goals for Health and Wellbeing here.
“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
“Hard work, dedication and endless opportunities, I can now say I am on the path to previously unimaginable goals. A dream come true! We are breaking the barriers that make Science seem unattainable, by being the link between Science and society, made possible by funding bodies like the GCRF START grant.”
Gugulethu Nkala, PhD student in the Energy Materials Research Group at the University of the Witwatersrand, South Africa.
Gugulethu Charmaine Nkala is a PhD student at the School of Chemistry in the Energy Materials Research Group at the University of the Witwatersrand (Wits), South Africa. From Roodepoort, west of Johannesburg, she is the eldest of three daughters, descending, she says, “from a line of great women, whose circumstances did not allow them to proceed to higher education”. Gugu’s great grandmother had to leave school at grade 7 (after she finished primary school) because as a woman it was only seen necessary to be able to write and read letters; Gugu’s maternal gogo (grandmother) was a domestic worker, and her parents were not able to study beyond high school. Gugu says, therefore, “It is with this in my heart, that I have been encouraged to go forth and reach places that their hopes and dreams could not take them. I have a story to tell, a story to finish.” Gugu is determined to share her story and be a role model to motivate women and girls to take up science.
Gugu’s research focuses on improving renewable energy storage systems to make them more efficient, affordable, safe and environmentally friendly in order to address the energy poverty gap in Africa, in line with the UN’s Sustainable Development Goals. Under the PhD supervision of GCRF START grant Co-I, Professor Dave Billing, Prof Caren Billing and Dr Roy Forbes, her particular interest is: ‘The Use of Fused Bimetal Phosphate-based Ceramics for Solid-State Electrolyte Applications’, through which she investigates batteries as energy storage devices for applications such as phones and tablets, with the aim of fabricating a solid-state electrolyte that can be used in an all-solid-state battery (a battery in which the electrodes and electrolyte are solid).
It is with the GCRF START grant, that Gugu has been able to visit the UK’s national synchrotron, Diamond Light Source (Diamond), and has also attended START related workshops and meetings which have furthered her research knowledge and skills, introducing her to international collaborations and research networks overseas and in Africa – experiences Gugu describes as “beyond invaluable in my studies” and a “privilege”. In the next few weeks, some of Gugu’s research materials are set for analysis using X-ray Absorption Spectroscopy (XAS) techniques on the B18 beamline at Diamond as part of a Beamtime Allocation Group (BAG).
Gugu is the first in her family to go to university, an achievement she attributes to the culture of her school and the support of her parents who invested in their children’s school education, leading her to become one of the top pupils in her school and developing her love of STEM.
“My grandmother encouraged my father to enable the education of the ‘girl-children’ in our family,” Gugu explains, “and I was interested in the physical sciences in particular – physics, chemistry, biology – subjects not many girls go for. From an early age I was inquisitive, and my parents nurtured that side and were engaging and supportive. This was formative, coupled with the school I went to which instilled discipline, resilience and, above all else, ‘the spirit of chasing one’s greatness’.”
Gugu’s aunt assisted with university fees in Gugu’s first year when Gugu’s father was retrenched as a machine minder in 2012, and what followed is a journey of tenacity and resilience into the world of energy materials science – an unusual career-path for a woman in Africa. Through bursaries and working hard in her vacations to fund her studies, despite various setbacks, Gugu has been able to accomplish her dreams and achieve great things. Testament to her hard work, she has received various awards and is now studying for her PhD, receiving mentorship from her supervisors and mentors, Prof. Caren Billing and Prof. Dave Billing and funded by a bursary.
“I was sold at an early stage on material science – I fell in love with it! Being part of Prof Dave Billing’s group helped me to look at things from different perspectives,” Gugu enthuses.
Gugu loves working with the Energy Research Group at Wits and collaborating with the GCRF START grant because she is encouraged to dream big and believe what some might seem is impossible to achieve for a young woman in Africa.
“Earlier in my academic career, I dreamed of being the head of a Research and Development department in South Africa. However, being in my research group with the teachings and mentoring of my supervisors has shown me that I can aim higher, dream the once impossible,” she explains.
Closing the energy poverty gap in sub-Saharan Africa
Gugu’s motivation behind her research project comes from the desire to find solutions to energy challenges in sub-Saharan Africa, starting in South Africa where a large population, especially in the rural areas, is still without access to basic commodities such as electricity, sanitation and health care, something that particularly impacts women. In these parts, firewood is still the most used source of energy for cooking, as well as paraffin lamps and candles for lighting. Approximately 80% of South Africa’s electricity relies on coal, with the resulting environmental challenges that this brings. Shifting the focus towards improving renewable storage systems (such as solar, wind, hydrology, and others) would be beneficial, not only to the planet but to the health and livelihoods of human populations.
In order to bring renewable energy sources into the energy mix, the focus of scientific research needs to be moved towards improving renewable storage systems such as batteries. The most widely used rechargeable batteries contain toxic electrolytes such as sulfuric acid in lead acid batteries and lithium perchlorate in lithium-ion (Li-ion) batteries. The drawbacks of current Li-ion batteries are, amongst others, their costs and reliability concerns, which are attributed to the deterioration of battery devices over relatively short periods of time. The constant replacement of these materials has a negative impact on the environment.
Commercial batteries use an organic liquid as an electrolyte and these organics compromise the safety of the battery. Increasingly, alternative electrolyte materials have received great attention, more specifically solid-state electrolytes. The use of solid-state electrolytes would eliminate the need for a separator, avoiding the use of organic electrolytes and therefore the use of safer batteries that do not pose any leakage risks.
In Gugu’s studies, she is working on a material based on the sodium (Na) superionic conductor (NASICON) structure type, namely lithium titanium phosphate LiTi2(PO4)3 (LTP). This involves investigating its properties as a potential material for a solid-state electrolyte in Li-ion batteries to address the challenges that arise from current batteries. Gugu’s research includes understanding the Li-ion conductivity of the class of materials being studied under different environmental conditions such as temperature, and how the materials behave in different atmospheres, specifically air and nitrogen, an inert atmosphere. The research also involves exploring ways in which lower cost batteries can be synthesised.
Breaking down barriers and giving back to the community – being a role model
Gugu’s involvement in university science outreach projects to schools has focussed on educating learners and teachers from different backgrounds about the importance of renewable energies. Organised through the Energy Materials Group, Gugu is enthusiastic about motivating and assisting young people from disadvantaged backgrounds to fulfil their dreams in the way she herself was encouraged from a young age to fulfil her goals. This is also a way for Gugu to give back to the community, as well as learn about community-based perspectives and how the Group’s research might impact everyday lives.
“Most of these children come from impoverished backgrounds and do not have role models in their society who they can look up to, to enable them to see that their dreams are not so far out of reach, and that their circumstances do not have to be a tight leash that keep them away from dreaming bigger,” Gugu explains. “Seeing a black girl in science, makes them see that there is someone, just like them, who has gone this far. We are breaking barriers that makes science seem unattainable, by being the link between science and society, made possible by funding bodies like the GCRF START grant.”
One of the outreach science demonstrations was a solar panel station where people could charge their phones. This enabled the scientists to explain the science behind solar panels, as Gugu describes below,
“The students were excited and astonished by the fact that one can use the sun to power their devices. Seeing their reactions and being part of something so special made me come back with the understanding of just how deep our impact in society could be, educating one child at a time.”
Attending ANSDAC workshops in Africa and visiting Diamond Light Source in the UK
In 2018, Gugu attended the first African Neutron and Synchrotron Data Analysis Competency workshop (ANSDAC), where the GCRF START grant is amongst the funding bodies. This workshop focuses on teaching African scientists about synchrotron techniques and how to analyse the results obtained, bringing in experts in different field techniques to ensure the best teaching possible. The students not only learn about synchrotron science but also how to analyse the data. Gugu also took an online course through Brookhaven Laboratory in the USA, which, she says, “forced us to push ourselves and the boundaries of science, making the best of whatever resources we had.”
From the 10-12 March 2020, just before the Covid-19 pandemic lockdown, Gugu was one of the attendees of the XAS workshop hosted and taught at Diamond on the Harwell Campus, the UK’s world-class innovation hub.
“Visiting Diamond in the UK was a life changing opportunity,” Gugu enthuses. “It took me from a position of remotely learning about synchrotrons and taking virtual tours, to experiencing this first-hand.”
“You read about it in textbooks,” she continues “and then I was standing in front of it and there was a glorious opportunity to take a tour inside the facility. One of the topics we covered at the ANSDAC workshop was XAS, so I already had a good basis for the workshop at Diamond. This background knowledge allowed me to learn more about the technique and the data analysis, starting from a position of knowledge, once again, enabled by the GCRF START grant. It was wonderful to consult the beamline scientists and do hands on tutorials; to be in the same room as the people one looks up to.”
Not only has the GCRF START grant enabled Gugu to visit the synchrotron of her dreams, but it has also fundamentally impacted her skills and abilities, and her perspectives on her future career path. Visiting Diamond, Gugu says, has shown her new horizons of learning which she wants to bring back to the science community in Africa.
“The GCRF START grant has enabled me to move forward from attending online courses by Brookhaven National Laboratories (Applications of Synchrotron and Electron-Based Techniques 2018) to actually running X-ray diffraction (XRD) – an analytical method used to determine the nature of crystalline materials – and atomic Pair Distribution Function experiments – an X-ray scattering technique that can be used to study the local structure of materials at the atomic scale,” explains Gugu. “This brings results that take us students closer to answering the fundamental questions in our projects, sharpening our focus and skills to work out what steps to take next in the future.”
Another goal achieved, she says, would be the opportunity to take up a postdoctoral position and work alongside beamline scientists at Diamond on X-ray Absorption Spectroscopy.
“Achieving this goal,” Gugu says, “would be the completion, or the start of my story, of my grandmothers’ stories. The story of Black Girl Magic!”
With the ongoing Covid-19 pandemic in 2020 and 2021, Gugu and her peers are thankful for the support of their supervisors, despite the challenges and delays that lockdowns and restrictions have brought, such as restricted access to campus to undertake experiments and having to book precious time slots to use laboratories.
“Our supervisors have been checking in on us regularly, encouraging us and helping us not to panic. They have been going above and beyond to try to ensure we have the software to process our data. This has been pretty amazing support,” Gugu reports.
Commenting on Gugu’s progress and ambitions, Prof Caren Billing says, “Gugu got back from attending an XAS training workshop at Diamond Light Source the week before our airports were closed due to the Covid-19 pandemic (March 2020). The visit to Diamond through the GCRF START grant has raised her expectations of herself and her work to new levels. She has been presenting talks at our group meetings to inform others of what she has learnt and brought a great amount of enthusiasm with her.”
 Prof Dave Billing is Professor in the School of Chemistry and Co-PI of the Energy Materials Research Group at the University of the Witwatersrand (Wits), South Africa, and also Assistant Dean in the Faculty of Science at Wits.
 Prof Caren Billing is Associate Professor in the School of Chemistry at the University of the Witwatersrand, South Africa
 The support of the DST-NRF Centre of Excellence in Strong Materials (CoE- SM) towards this research is hereby acknowledged. Opinions expressed and conclusions arrived at, are those of the author and are not necessarily to be attributed to the CoE- SM.
Luo, X., Wang, J., Dooner, M. and Clarke, J., 2015. Overview of current development in electrical energy storage technologies and the application potential in power system operation. Applied Energy, 137, pp.511-536.
“Now we have built up the base for computer modelling here in Southern Africa, the GCRF START grant will help us take experimental science, simulations and knowledge exchange even further, building on 30 years of successful collaboration between African and UK scientists to address global energy and climate challenges.”
Prof. Phuti Ngoepe, GCRF START Co-Investigator, University of Limpopo, South Africa
Long-standing collaborations with the UK research community have demonstrated the mutual positive impact from partnerships which benefit from unique African perspectives. Spanning more than 30 years, one such partnership is the research collaboration between Professor Phuti Ngoepe, Director of the Materials Modelling Centre at the University of Limpopo (UL) in South Africa, and Professor Sir Richard Catlow, Professor of Catalytic and Computational Chemistry at the University of Cardiff and Professor of Materials Chemistry at University College London in the UK.
Initially funded by The Royal Society, London (UK), and South Africa’s National Research Foundation (NRF), the collaboration between Prof. Catlow and Prof. Ngoepe has afforded many UK and African scientists opportunities over the years to share skills, build capacity, and get involved in diverse and sustainable projects related to energy storage, mineral processing and alloy development, including recently, with the GCRF START grant, of which both Prof. Ngoepe and Prof. Catlow are Co-Investigators.
With the GCRF START grant, Prof. Catlow and Prof. Ngoepe are shaping a future legacy built on shared knowledge and past achievements, where emerging scientists in Africa and the UK are trained in the latest synchrotron techniques, and experimental synchrotron science complements cutting edge simulations.
The building of a legacy: UK-Africa scientific collaboration and capacity building
The collaboration between Prof. Catlow and Prof. Ngoepe is notable for its many achievements with fruitful outcomes that have been mutually beneficial, not only for the research interests of both scientists, but also in the building of strong teams of simulations experts and improvements in computer modelling and experimental science in Africa and the UK. This has been demonstrated right from the beginning of the partnership, Prof. Ngoepe says, where UK methodologies in energy material simulations were influenced by knowledge exchange between South Africa and the UK.
“At the start of the collaboration, South African minerals were not that “friendly” to the existing modelling techniques in the UK, especially the minerals that work,” Prof. Ngoepe recalls. “This prompted us to introduce and improve the methodologies of the simulations to address these challenges, which helped the simulations in the UK to advance to where they are today. We jointly extended this experience to other African countries, with science advocacy roles forged in institutions across the continent. Richard and I went to Ghana together and to Botswana, and with the experience we built were able to reach out and develop capacity in these countries in the area of simulations. Because of this common experience, when South Africa established its National Centre for High Performing Computing, we were able to bring other African countries on board.”
Technology development has marched forward at lightning speed since then and the collaborative work of the two scientists has diversified successfully into many interesting applications with effective capacity building leading to several researchers involved in the collaboration holding prominent positions in South Africa. A particular highlight is Prof. Ngoepe’s success in setting up a leading Computational Materials Modelling Centre (founded in 1996) at the University of Limpopo – a university that was disadvantaged in the pre-1994 Apartheid dispensation and historically under-resourced for research and innovation. Located in a mainly rural region, the University of Limpopo still predominantly caters for students from disadvantaged backgrounds and rural areas. However, over recent years, it has developed successful capacity building approaches relevant to many developing countries and from which the group at UL’s Materials Modelling Centre has benefitted.
Through the combined efforts of Prof. Ngoepe, Prof. Catlow and others, new concepts such as Post-Doctoral Researchers and Research Associates were introduced into the Centre’s institutional environment in addition to the advantages of linking researchers to relevant practical initiatives and extending research to address challenges of those programmes, as well as assistance with basic needs such as accommodation and tuition costs. The result has been the promotion of a critical mass of Master’s and PhD students from previously disadvantaged backgrounds through the retention of good students with high computing skills who might otherwise have left research due to financial and other constraints. Today, UL’s Computational Modelling Centre is considered “one of the leading centres within South Africa’s Higher Education landscape where computer modelling is conducted on material for a broad range of industrial applications, such as energy-storage devices, minerals and metal alloys.”
Another achievement of the collaboration between the two scientists is the successful programme of joint conferences at the University of Limpopo and exchange visits by South African and UK students, which has helped shape knowledge and practice in both countries in fundamental ways. “In extending the cyber infrastructure capacity, relations that were formed during the exchanges with fellow postgraduate students in the UK over many years, have and still help to facilitate knowledge, practices and expertise in this ever-expanding field,” Prof. Ngoepe explains.
“It has been hugely rewarding working with Phuti and colleagues and with other African scientists over the last 30 years,” says Prof. Catlow, “I first visited the University of the North (now University of Limpopo) in autumn 1994. I met Phuti and a young colleague working enthusiastically in a small computer lab with one Silicon graphics machine. Over the ensuing decades we have seen develop, from this very modest beginning, a strong and successful centre that has not only produced excellent science but has populated, universities and research centres with its graduates. And I am very pleased and proud that UK scientists were able to contribute to this remarkable achievement.”
Dr Happy Sithole is the Director of South Africa’s Centre for High Performance Computing (CHPC) and Center Manager of the South African National Integrated Cyberinfrastructure System (NICIS). His story, says Prof. Ngoepe, is “a fantastic example of the way this international exchange and collaboration can have a lasting impact”. Dr Sithole obtained his PhD at the University of Limpopo under Prof. Ngoepe and Prof. Catlow’s UK-South Africa collaborative exchange programme early on in his career, the impact of which he describes below.
“I received my PhD through this collaboration, which made it possible to work with various experts in the UK, such as the late David Pettifor, Steve Parker and Kate Wright,” Dr Sithole recalls. “What this really presented was infinite imagination of problems that could be solved. The various expertise enabled me to cover all different aspects of mineral processing and not limiting me to only understanding the properties of materials. I have managed to expand my initial PhD thoughts into what now could be called the bedrock of mineral processing through modelling and simulation, backed by experimental proof. This also presented an opportunity for UK institutions to expand their software and tools to study new problem areas that were proposed by the Materials Modelling Centre in South Africa. I have seen the evolution of METADISE driven by the continued surface requirements of Platinum Group Metals. I am currently heading the National Integrated Cyber-Infrastructure in South Africa, which thrives through collaboration with UK institutions, and contributes to other activities in the UK. It is a mutual benefit between the two countries.”
Dr Sithole has taken teams of scientists and won awards at international meetings and continues to maintain the partnerships he formed with scientists in the UK, which have since deepened and expanded.
Extending the legacy with GCRF START – innovative science and a new generation of science leaders
Building on this legacy, the GCRF START grant has given Prof. Ngoepe and his group momentum to set up new, ground-breaking projects that will radically increase and speed up what the group is able to achieve, providing the means to train and mentor a new cohort of emerging scientists skilled in the latest experimental and theoretical techniques. One of these initiatives aims to advance the group’s research on battery cathodes through the setting up of a new Li-ion Battery Cathode Synthesis Laboratory at the University of Limpopo (currently being commissioned after an initial delay due to the Covid-19 lockdown). The Li-ion Battery Cathode Synthesis Laboratory will provide the group with their own samples to be studied using the UK’s Diamond synchrotron with access provided by the GCRF START grant.The ultimate goal is to contribute to global efforts to produce safe, cheap, ‘green’ batteries with a longer life cycle, increased storage capacity, a wider optimal temperature operating range, and higher power output.
High energy density batteries are central to development of electric vehicles, solar energy storage and electricity utility backups – crucial in mitigating adverse effects of global climate change. Currently, computational modelling studies of manganese-based battery cathodes are explored such as the spinel lithium manganese oxides and manganese rich NMCs of these. Predicting structural stabilities is vital, especially during charging and discharging in order to ensure long life of the batteries. These predictions guide where to put emphasis on experiments, and aid in the interpretation of results. “For this, access to the Diamond synchrotron with the GCRF START grant will be of enormous value,” Prof. Ngoepe explains, “bringing many new dimensions to what we can do within our group.”
“The START grant will enable innovative research insights emanating from comparison of the simulations done by Prof. Ngoepe’s group at the University of Limpopo’s Materials Modelling Centre with synchrotron experimental results,” says Prof. Catlow. “Synchrotron science is an absolutely key area of contemporary science across the board and GCRF START is producing a trained workforce in this field. It is the development of people with expertise in leadership which makes it possible to develop cutting edge facilities and innovative science. We hope that the development of these skills will help to provide support and momentum for the African Light Source project which aims to develop a synchrotron facility on the continent.”
In terms of investing in people, GCRF START grant acts like a catalyst in the training of emerging young scientists to be future science leaders. This is made possible through exchanges and workshops, access to world class equipment and facilities, and mentoring by experts, along with financial and practical support. Within Prof. Ngoepe’s group at UL’s Materials Modelling Centre, there are more than ten students being equipped in this way through exploring simulations of various energy storage areas, ranging from cathode, anode and beyond to lithium-ion battery materials.
Dr Clifton Masedi is a START Post-Doctoral Research Fellow working together with postgraduate students in the Materials Modelling Centre alongside Dr Noko Ngoepe who oversees experimental aspects of the synthesis of cathode materials earmarked to be linked with the Diamond synchrotron. With a background in computational modelling of energy storage materials, Dr Masedi is investigating stabilities of NMC cathode materials and lithium sulphur for batteries using universal cluster expansion methods and will initially use the samples grown from the synthesis laboratory at UL for synchrotron studies and compare them with simulations. By bringing students in the Materials Modelling Centre to work closely with Dr Masedi, the plan is to expose more students to synchrotron science.
“With the GCRF START grant, the process of combining synchrotron science with computer modelling/simulations, enables a critical number of people to be trained in foundational and synchrotron techniques, whilst doing very interesting science. Such exposure is motivational and extends scientific and cultural outlook,” says Prof. Ngoepe. “The goal with the GCRF START grant is to extend these insights to more students in the future, thus developing a trained workforce in contemporary scientific techniques while continuing our collaboration with the UK for generations to come.”
This approach is whole-heartedly endorsed by Dr Sithole who points out that, in the past, Prof. Catlow and Prof. Ngoepe’s efforts followed a similar path, leading to the successful, sustainable impact seen today.
“In line with linking experimental facilities such as the synchrotron to modelling and simulations, I believe this is one of the core ingredients of the success of your previous collaboration. Embedding Human Capital Development in this process cannot be over emphasised, as this is the heart of sustainability of the collaboration,” says Dr Sithole. “We have learnt this through the collaboration under the National Research Foundation and The Royal Society, where a strong team of simulation experts was built in South Africa – in particular at the University of Limpopo – and which elevated the institution’s research capacity now visible through the Materials Modelling Centre. The linkages built during this period continue to function within institutions in the UK and South Africa. I am looking forward to participating in this [GCRF START] collaboration and believe South Africa will be able to bring to the table computational resources and skills which were built through the initial collaboration and further expanded to the bulk of the African continent, making this GCRF START project an even better collaboration.”
About Professor Phuti Ngoepe
Prof. Phuti Ngoepe is a GCRF START Co-Investigator and Senior Professor and Director of the Materials Modelling Centre at the University of Limpopo in South Africa, where research focuses on the prediction of the properties of minerals, light and precious metal alloys, and energy storage materials used mostly in lithium-ion batteries. Prof. Ngoepe’s team has contributed novel work on the simulated synthesis of nanostructures for lithium-ion and newer lithium-air batteries. Simulations are used to predict the performance of such structures, by calculating their voltage profiles, microstructures and mechanical properties. A Founder Member of the Academy of Science (South Africa), Prof. Ngoepe holds the South African Research Chair (SARChI) on Computational Modelling of Materials and has served on the boards of a number of prominent science councils including the National Research Foundation (South Africa), Mintek and the Council for Geosciences, amongst others. Prof. Ngoepe has participated in many science strategy committees and reviews of government institutions and programmes, and in bilateral science and technology missions which have taken him, among others, to the USA, Russia, Japan, China and countries in the European Union. In 2008, Prof. Ngoepe was awarded the South African Presidency’s highest honour – the Order of Mapungubwe Silver for “excellent achievements in the field of the natural sciences and contributing to the development of computer modelling studies at the University of Limpopo”.Click here for a full biography.
Prof. Sir Richard Catlow is Foreign Secretary and Vice President at The Royal Society, London (UK), Professor of Catalytic and Computational Chemistry at Cardiff Catalysis Institute (UK) and Professor of Chemistry at University College London (UK), and a GCRF START Co-Investigator. He is also a co-founder of the UK Catalysis Hub. Professor Catlow develops and applies computer models to solid state and materials chemistry — areas of chemistry that investigate the synthesis, structure and properties of materials in the solid phase. Richard’s work has provided insight into mechanisms of industrial catalysts, especially involving microporous materials and metal oxides, as well as how defects — missing or extra atoms — in the structure of solids can result in non-stoichiometric compounds. “Simulation methods are now routinely used to predict the structures of complex solids and silicates, respectively, thanks to Richard’s demonstrations of their power. By combining powerful computational methods with experiments, Richard has made considerable contributions to areas as diverse as catalysis and mineralogy.”
Dr Sithole is the director of the Centre for High Performance Computing at South Africa’s Council for Scientific and Industrial Research (CSIR) and Centre Manager of the South African National Integrated Cyber-Infrastructure System (NICIS). He completed his PhD at the University of Limpopo focusing on electronic and atomistic simulation of iron sulphides. Dr Sithole has applied high-performance computing to solve problems in mining industries and nuclear power plant designs. He sits on various high profile local and international high-performance computing committees.
“Over the past two years, being involved in the GCRF START grant has allowed me to mature and to become much more independent as a scientist.”
Dr Camien Tolmie, University of the Free State, South Africa
The molecular workings of the natural world have always interested me, especially how we can use these processes to sustainably improve human health and agriculture. My name is Carmien Tolmie and I grew up in the small city of Bloemfontein, in the Free State province of South Africa. From a young age, I enjoyed maths, science and languages, and I participated in various extracurricular academic activities in STEM. As a result, I decided at an early age to pursue a career in science, starting with a BSc degree in Molecular Biology and Biotechnology at the University of Stellenbosch, and returning to Bloemfontein for my postgraduate studies (BSc Honours degree, MSc and finally PhD) at the University of the Free State (UFS), where I chose Biochemistry as my discipline.
Structural Biology is an incredibly powerful and multi-functional field with various applications in human health, agriculture and sustainable ‘green’ chemistry (environmentally friendly chemistry). Passionate about addressing the challenges I see in Africa, I was motivated to undertake my PhD with Prof. Dirk Opperman who is a GCRF START Co-Investigator (Co-I) in UFS’s Biocatalysis and Structural Biology research group, working on enzymes (proteins that act as biological catalysts) from Aspergillus flavus. The Aspergillus flavus fungus grows on agricultural crops, produces cancer-causing compounds and can also cause infectious fungal disease. Studying the atomic structures of proteins from fungi like the Aspergillus flavus reveals a wealth of information, such as how the three-dimensional structure looks and changes during the chemical reactions it catalyses, the possible mechanism of how the protein works, and how it binds to small molecules. If the protein is a drug target, the structure can be used in Structure-Based Drug Discovery to develop new medications, ‘green’ pesticides for agriculture, and other applications.
Passing on the love of learning to other young scientists
I love learning and discovering new things, working in the lab, as well as passing on the knowledge to others. Therefore, I decided to build a career in academia with a focus on Structural Biology. I have recently been appointed as a full-time academic in UFS’s Department of Microbial, Biochemical and Food Biotechnology (January 2020) where I have a joint research and teaching position as Lecturer in Biochemistry. In my new fungal drug discovery projects, which I have just started (delayed because of Covid19 lockdown), I am the main Principal Investigator (PI) in collaboration with Prof. Opperman and Prof. Martie Smit.
My new research projects will look specifically at developing inhibitor compounds against fungal metabolic targets with the aim of discovering new antifungal compounds. Existing anti-fungal medication and pesticides have been so widely used that fungi have evolved and developed ways to combat the anti-fungals, thereby becoming drug resistant. Our research may help in the future to develop sustainable solutions through novel antifungal drugs to improve the health, wellbeing and prognosis of people who suffer from infectious fungal disease, particularly immune-compromised patients, where fungal infections can cause serious health complications and can be life threatening.
To conduct the research, I will use the structure-based drug discovery method of X-ray crystallographic fragment screening at the UK’s national synchrotron, Diamond Light Source (Diamond). This method uses protein crystals of the target enzyme to identify small molecule fragments that bind to the enzyme. These fragments are then elaborated into larger molecules with higher potency, which will hopefully not only inhibit the specific enzyme, but also the growth of pathogenic fungi. I was introduced to the concept and power of fragment screening techniques during GCRF START meetings and learnt more about the experimental workflow of XChem and the I-04 beamline during my research visit to Diamond Light Source in the UK last year, which inspired me to embark on XChem projects for antifungal drug discovery.
Investing in African Early Career networks through GCRF START grant
“Carmien is not only passionate about Structural Biology, but also teaching. She has been a vital part of START, helping and teaching the postgraduate students not just in our lab, but also reached out and helped other GCRF START groups in South Africa.”
Prof. Dirk Opperman, University of the Free State
Being involved in the START grant has made a very concrete contribution to my career as a young scientist. At the beginning of the START project, I was a PhD student with Prof. Opperman. The START grant has contributed to the running cost of our laboratory, funded my postdoctoral salary for 2019, as well as my travel cost of attending a CCP4 workshop in Brazil (2018), the Biophysics and Structural Biology at Synchrotrons workshop, and various START meetings. The grant also enabled and funded my research exchange to the UK last year (2019). Through START, we have met numerous top-notch scientists that can advise us on our experiments. We have START meetings for early career scientists, both in the Structural Biology and Energy Materials strands of the START project. We routinely collect data with other members of the South African Structural Biology Consortium at Diamond (various universities and START collaborating laboratories), albeit through remote access – a process that was greatly improved by a Data Collection Workshop run by Diamond’s beamline scientists in Pretoria last year, and which enhanced our data collection skills and deepened our relations within the network established by START.
Interestingly, this international collaboration has been instrumental in establishing a network of early-career structural biologists in South Africa, including postgraduate students and postdoctoral researchers. Getting to know peers who are working in Structural Biology, and who are using the same techniques as I am, and who have similar research interests has provided a feeling of connectedness. These projects are often very demanding and having the support and motivation of a friend who has encountered similar setbacks (or being that friend to someone else) can really help one endure in difficult times. My hope is that this network will be the basis for many future collaborations.
Exposure to international research collaborations and facilities
GCRF START has exposed me to many esteemed international scientists and facilities. The START events have introduced me to scientists at Diamond who are very supportive and who have invested in both the START project and the development of the people involved in the project, such as START Co-I, Prof. Frank von Delft, who has research groups at both Diamond and the Structural Genomics Consortium at the University of Oxford. I was hosted by the Structural Genomics Consortium for a two-month research exchange last year to develop new experimental skills and this kind of exposure has greatly improved my skills and the way I think about my research.
At the time of writing, I am currently involved in organising a crystallographic data processing workshop in South Africa – the first of its kind to be held on the continent – with START and CCP4. The workshop was supposed to be in April of this year (2020) but had to be postponed because of the Covid19 pandemic. I am one of the main local organisers, and this has given me the opportunity to improve both my grant-writing skills and organisational skills. In addition to funding by CCP4 and START, we have secured funding from the International Union for Crystallography, the International Union for Pure and Applied Physics, the National Research Foundation of South Africa, and the University of Cape Town.
Gaining the competitive edge!
Over the past two years, being involved in the grant has allowed me to mature and to become much more independent as a scientist. My appointment as a Lecturer in Biochemistry means starting with my own, independent research projects in Structure-Based Drug Discovery, which is very exciting, and scary at the same time! I will be responsible for the second-year undergraduate Biochemistry module – Enzymology and introduction to metabolism. Although this is a difficult year to start teaching a module, I have a great support system at the department. I truly believe that the experience and exposure of START gave me a competitive edge in being selected for the position, and I am very grateful for this opportunity.
“The opportunities that were afforded to Carmien through the GCRF START grant enabled her to transition to academia. For the momentum we have gained through the grant to continue, we must transition our START Post Graduate Research Assistants into permanent academic positions. This allows us to retain the ‘critical mass’ required for structural biology to be successful in South Africa.”
Prof. Dirk Opperman, University of the Free State, South Africa
Click here to read more about the UN’s Sustainable Development Goals
I would firstly like to thank Dirk for the motivation, support and academic mentoring throughout the years; I would not have been the researcher I am today without him. I would like to thank Prof. Trevor Sewell (Director of the Aaron Klug Centre for Imaging and Analysis, University of Cape Town), Dr Ruslan Nukri Sanishvili (formerly of Argonne National Laboratory, Chicago, USA), Dr Gwyndaf Evans (Deputy Director Life Science, Diamond Light Source), Dr Dave Hall (MX Group leader, Diamond Light Source), and the CCP4 staff for their help in organising the CCP4 workshop. I would also like to thank Prof. Frank von Delft (Diamond Light Source, University of Oxford) and Dr Nicola Burgess-Brown (University of Oxford) for hosting me in their research groups. Finally, I would like to thank the University of the Free State and especially Prof. Martie Smit (HOD, Dept. of Microbial, Biochemical and Food Biotechnology) for giving me the opportunity to further my academic career.
Tolmie C, Do Aido Machado R, Ferroni FM, Smit MS and DJ Opperman (2020). Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation. Catalysts 10(3): 339. doi: 10.3390/catal10030339 (Impact factor 3.444): https://www.mdpi.com/2073-4344/10/3/339
“I think we, as African scientists, have a lot to offer. We are very connected and very close to the problems of the world. On a daily basis, we witness many of the global challenges first-hand and see the impact of diseases like HIV/AIDS, TB, Malaria, cancers and other communicable, as well as non-communicable diseases. We can see directly how our research can be life-saving. This is a big motivator!”
Melissa Marx, University of Cape Town, South Africa
To me, the GCRF START grant means the ability to learn new techniques which I can apply in my research on the human papillomavirus (HPV) 16 pseudovirions (PsVs) at the University of Cape Town (UCT). I’m using the structural biology technique cryo-electron microscopy (cryo-EM) to image HPV16-PsVs particles in order to obtain a better idea of the entry mechanisms used by the virus to infect host cells. With the help of the START grant, I can use techniques for research that could potentially contribute to the development of inhibitors for HPV infection, thereby decreasing HPV-associated cancer incidence down the line. This is really exciting and topical because cervical cancer – almost always caused by oncogenic HPV infection – is one of the most common cancers in women globally and the HPV is the second most frequent cause of cancer among women in Africa and in my own country of South Africa. My research and the START grant are therefore very important to me personally, as well as for women in Africa in general.
As a ‘newbie scientist’ in the early stages of my career, it is important to be exposed to different techniques that we wouldn’t normally be exposed to here in Africa. In my undergraduate degree, I had almost no exposure to electron microscopy and computer software in general. Fast forward to the present as a first year MSc student, and after only one year of experience in this field (and lots of help), I’ve managed to make three reconstructions of HPV particles using two different reconstruction programs and have made large numbers of grids on which we mount the samples! Within South Africa, there isn’t a lot of information about cryo-EM and other techniques we need to use for our research. Through the grant, I have been able to learn things like negative staining, vitrification, sample purification, sample preparation, and data analysis using RELION, and I even had the opportunity to go overseas to visit the UK’s national synchrotron, Diamond Light Source (Diamond).
Why developing Inhibitors for HPV could be the way forward
“Melissa’s project is the result of a fruitful collaboration with the Electron Microscopy Unit at the University of Cape Town which adds exciting new approaches to study and target viral entry mechanisms.”
Dr Georgia Schäfer, University of Cape Town, South Africa
Human Papillomavirus (HPV) is one of the most commonly diagnosed sexually transmitted viruses worldwide, and infection with high risk types has been linked to several cancer types, most notably cervical cancer, as mentioned above. In Africa, an estimated 372.2 million women aged 15 years and older are at risk of developing cervical cancer; every year, 119,284 women across Africa are diagnosed with cervical cancer and 81,687 women die from the disease, as reported by the HPV Centre report on HPV in Africa, 2019. In my own country of South Africa, cervical cancer is the first most common female cancer in women aged 15 to 44 years and one of the leading causes of cancer related deaths [1-6]. Although HPV vaccinations exist and are safe, these vaccines are only protective to HPV uninfected adolescents, making them ineffective for persons already infected with HPV [7,8].
The vaccines are also relatively expensive and need repeat doses [7,9,10]. This creates a difficult situation for many people, who may not be able to afford repeat treatments or do not have easy access to health care facilities. In addition, rural communities in South Africa are largely unaware of HPV infection as a risk factor for cervical cancer, which has made vaccine distribution ineffective, with little of the South African population vaccinated between 2009 and 2014 . Developing medication to prevent HPV infection by blocking the entry of HPV into susceptible human cells could be an alternative to vaccination, and another opportunity to reduce the amount of HPV associated cancers within South Africa and worldwide.
In our laboratories at the University of Cape Town we have identified two human proteins, surfactant protein A (SP-A) and vimentin, which decrease HPV infection by modulating viral entry into susceptible cells  or by activating the innate immune system, respectively. This research took place in UCT’s Electron Microscope Unit at the Aaron Klug Centre for Imaging and Analysis and Division of Medical Biochemistry and Structural Biology (Institute of Infectious Disease and Molecular Medicine). To determine which portions of these two proteins interact with HPV, electron microscopy imaging and 3D reconstruction studies of HPV particles pre-incubated with each of these two proteins are being conducted. From this, and further biochemical tests, we can determine the relevance of these interactions for HPV infection, with the potential to develop inhibitors for HPV infection of susceptible human cells.
Using Diamond Light Source synchrotron to image our HPV samples
In order to carry out this research access to state-of-the-art imaging equipment is vital. The GCRF START grant has made this possible, by providing our researchers and collaborators with access to the Electron Bio-imaging Centre (eBIC) embedded at Diamond Light Source. My visit to the Diamond synchrotron to conduct experiments for my research took place from the 9 – 11 October 2019. We had done the sample preparation at the University of Cape Town and had shipped the HPV samples in liquid nitrogen to Diamond a few weeks previously, so they were there once we arrived. The HPV samples were loaded onto the Diamond M06 Titan Krios electron microscope with the help of eBIC staff before imaging them using the transmission electron microscopy (TEM) technique.
Unfortunately, there are no equivalent facilities available on the African continent, and only a handful available worldwide, so I feel unbelievably fortunate to have been to Diamond – not just as someone from overseas on a tour but to have the experience as a researcher of working in and around such an innovative environment. The research and the equipment available are cutting edge and incredibly motivating to a young scientist. In addition to this, the scientists and staff are friendly and easy to engage with, and I found myself having conversations with researchers from all fields, not just biology.
Having a central research hub with scientists from different academic backgrounds, such as the materials sciences, biology, physical sciences, chemistry and others, creates a co-operative space and is likely to benefit anyone who participates. Being at Diamond Light Source and the Harwell Campus made me realise that having such a research hub is essential to science, aside from making things easier logistically! It was an incredible experience to be at Diamond Light Source, and I don’t think I could thank everyone involved enough for all the support and guidance along the way.
Most importantly, I would like to thank Dr Jeremy Woodward, who is a GCRF START Co-Investigator – for the time and effort he was willing to put into this project; I really wouldn’t be anywhere without him. I am also grateful to my supervisor, Dr Georgia Schäfer, for her help and encouragement, especially when producing the HPV16 particles at such short notice! I am also grateful to GCRF START Co-Investigator, Prof. Trevor Sewell, and Dr Andani Mulelu (previously a GCRF START-funded Postdoctoral Research Fellow), and to Dr Lubbe (currently a START-funded Postdoctoral Research Assistant); thanks also to Dr Sarron for all the advice and reassurance – which really helps! Lastly, I would like to thank the staff of the Electron Microscopy Unit at the University of Cape Town, especially Mohammed Jaffer, and the eBIC staff – James Gilchrist and Alistair Siebert – all of whom were very cheerful and accommodating when using the different microscopes. I even had a good enough sample for me to travel to Diamond, with the help of my two brilliant supervisors, Dr Georgia Schafer and Dr Jeremy Woodward, without whom, I might have been completely lost!
My science career so far..
I’ve always had an interest in biology, and I was fortunate enough to have parents who encouraged my interest, although they didn’t always know what I was doing! I began my scientific journey by completing a Bachelor of Science at Stellenbosch University (South Africa) in biochemistry and physiology. I then moved to the University of Cape Town for my Honour’s and Masters’ degrees. I was exposed to structural biology during my Honour’s degree, but I was somewhat intimidated by all the physics and maths involved. So, I only became involved in structural biology during the first year of my Master’s degree, at the Biophysics and Structural Biology at Synchrotrons 2019 conference (Cape Town, South Africa). I am currently completing my MSc in Medical Biochemistry and Structural Biology, under the supervision of Dr Georgia Schäfer and Dr Jeremy Woodward, within the Electron Microscopy Unit at UCT.
Click here to read more about the UN’s Sustainable Development Goals
1. Trottier, H. and E.L. Franco, The epidemiology of genital human papillomavirus infection. Vaccine, 2006. 24 Suppl 1: p. S1-15.
2. de Villiers, E.M., et al., Classification of papillomaviruses. Virology, 2004. 324(1): p. 17-27.
3. Chikandiwa, A., et al., Patterns and trends of HPV-related cancers other than cervix in South Africa from 1994-2013. Cancer Epidemiol, 2019. 58: p. 121-129.
4. Munoz, N., et al., Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med, 2003. 348(6): p. 518-27.
5. Walboomers, J.M., et al., Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 1999. 189(1): p. 12-9.
6. Bruni, L., et al., Global estimates of human papillomavirus vaccination coverage by region and income level: a pooled analysis. Lancet Glob Health, 2016. 4(7): p. e453-63.
7. Draper, E., et al., A randomized, observer-blinded immunogenicity trial of Cervarix((R)) and Gardasil((R)) Human Papillomavirus vaccines in 12-15 year old girls. PLoS One, 2013. 8(5): p. e61825.
8. Hildesheim, A., et al., Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment. Am J Obstet
9. Schiller, J.T., et al., An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Vaccine, 2008. 26 Suppl 10: p. K53-61.
10 Biryukov, J. and C. Meyers, Papillomavirus Infectious Pathways: A Comparison of Systems. Viruses, 2015. 7(8): p. 4303-25
“The GCRF START grant has been a game-changer for young African scientists, particularly from underrepresented groups such as female, and black scientists, enabling them to enter the field of Structural Biology and thrive. This has been achieved by collaborations from Africa and the UK, outstanding workshops on research techniques, international conferences, symposia hosted in Africa, and the recruitment of African scientific officers and postdoctoral fellows.”
Prof. Edward D. Sturrock, University of Cape Town, South Africa.
GCRF START –belonging to a diverse group of African scientists
My name is Lizelle Lubbe and I am a GCRF START Postdoctoral Research Fellow. My field of research is Structural Biology, which is a scarce skill in Africa with only a handful of scientists trained in single particle cryo-EM – a cutting-edge technique for determining the structure of proteins. START provides me with the opportunity to learn from these science pioneers in Africa, as well as from experts in the UK by establishing networks for discussion and organising workshops for hands-on training. Furthermore, GCRF START provides us with the resources to conduct outreach, not only to make science accessible for the community but also to inspire the future generation of scientists. I find it very stimulating to be a part of such a diverse group of scientists who are all working together towards achieving common goals to uplift communities and find solutions to global challenges.
Structural Biology combines concepts of Biology, Chemistry and Physics and therefore can be quite daunting to enter. For example, the design of drugs for the treatment of disease requires one to understand how the disease develops, identify a drug target in this process, use medicinal chemistry to design a small molecule capable of blocking that target, and validate the process using structural techniques. Although this has traditionally been a more male-dominated field, the hardships endured by women in science throughout history have led to ground-breaking discoveries and a paradigm shift, so that today I have the privilege of doing my postdoctoral research using revolutionary techniques like cryo-EM.
As a result of the GCRF START grant, I am funded to do my research which includes associated travel costs for data collection, access to mentoring from experts in their field, and the use of state-of-the-art equipment and facilities such as the UK’s national synchrotron, Diamond Light Source, and the GCRF START Centre for Excellence in the University of Cape Town’s (UCT’s) Aaron Klug Centre for Imaging and Analysis. START has made it possible to gain valuable and much sought-after experience and skills in biophysical and synchrotron techniques.
Improving the health of patients with hypertension and other diseases
My research is focused on a protein called angiotensin-converting enzyme (ACE) which is well-known for its role in blood pressure1 regulation. It is found in many organs throughout the human body where it catalyses a reaction to produce a peptide (string of amino acids) that causes constriction of blood vessels, thereby regulating blood pressure and circulation. In some cases, however, this process goes awry, and the blood pressure becomes elevated, increasing the force of blood against the artery walls. This condition is known as hypertension and typically does not produce any noticeable symptoms.
According to the World Health Organisation, 1.13 billion people suffer from hypertension globally2, with many countries in Africa3 experiencing the highest prevalence of hypertension in the world at 27% (WHO, 2019). Conditions caused by hypertension include stroke, heart failure, heart attack, kidney failure and loss of vision. There are many risk factors to hypertension, and these include family history, increasing age, stress, being overweight/obese, a diet high in salt, smoking tobacco, drinking too much alcohol, and a lack of exercise. Given the important role of ACE in blood pressure regulation, ACE inhibitors are commonly used in the clinic to effectively treat hypertension and heart/kidney disease. The use of ACE inhibitors is unfortunately linked to the development of side effects in some patients. It can be mild (loss of taste, skin rash or persistent dry cough) but also life-threatening in the case of angioedema. Angioedema is a condition where the patient develops severe swelling below the skin surface which can affect the throat, tongue and lips and obstruct the airway.
I am motivated by the potential of the research we are doing to improve the lives of patients living with hypertension and other diseases associated with ACE by increasing our understanding of the disease-causing protein. This would ultimately allow us to design ACE inhibitors with less side-effects. It is also very exciting to learn structural biology techniques such as cryo-EM and to help establish this expertise in Africa for the benefit of our community. By gaining valuable experience in the scarce field of Structural Biology, I hope to strengthen research in Africa and motivate others towards a career in science.
Inspired into biochemistry – persistencepays off!
The motivation I describe above started at a young age, and I was greatly inspired by my parents who both studied science – my mother studied Microbiology and my father, Mechanical Engineering. I grew up on a small farm outside Pretoria in the Gauteng province of South Africa and have been interested in the mechanism of action of therapeutic drugs from a young age. Opportunities for women in science were scarce in the early 1990’s and my mother could unfortunately no longer pursue her career after my birth. Her interest in the world of microorganisms remained, however, and inspired me to enter the field of Biochemistry where one could not only study microorganisms and other factors in relation to disease but also design therapies.
I had very limited hands-on exposure to science at the farm school I attended. My siblings and I spent many afternoons in the community library and at some point, I started reading encyclopaedias and became fascinated with science. After that, I saved some money and bought myself a second-hand toy light-microscope which occupied me for hours. However, these years were not without hardship. After obtaining his degree in Mechanical Engineering, my father single-handedly established a small business and it was very challenging to secure an income, so we were often left without certain essentials. Our school tuition was funded by government subsidies and as we could not afford private healthcare, I spent many school days in long queues since before the crack of dawn at the local District Hospital.
During my final year at high school (matric), the Physical Sciences teacher told me about the field of Biochemistry and although my parents could not afford to pay for my tertiary education, I was determined to obtain a degree and arranged to get a student loan. Persistence paid off and I obtained my undergraduate Bachelor of Science (BSc) degree at the University of Pretoria majoring in Biochemistry and Chemistry in 2011.
Great mentors – learning key Structural Biology techniques from GCRF START experts
These challenges and hardships only cemented my determination to continue in the field I am passionate about and having experienced mentors has really helped. My PhD at the University of Cape Town was supervised and co-supervised by Prof. Ed Sturrock and Prof. Trevor Sewell, respectively. They are both Co-Investigators on the GCRF START grant and, after finalising my PhD thesis, Prof. Sturrock offered me a GCRF START Postdoctoral Fellowship on a related research project in his laboratory. I started as a GCRF START postdoc in October 2018 and, in October 2019, I travelled to the UK to the Harwell Campus, and collected a dataset of ACE at the Electron Bio-Imaging Centre (eBIC) at Diamond Light Source using a Titan Krios transmission electron microscope with K3 detector. I am in the data analysis stage right now.
Professor Sturrock4 is a leader in the design of anti-hypertensive drugs and was an excellent mentor during my BSc (Med)(Hons) in Medical Biochemistry (completed in 2012) and PhD in Chemical Biology (completed in 2018) studies. He has taught me how to think critically about the problem at hand and to persevere despite the numerous setbacks one experiences as a scientist. For example, Structural Biology techniques such as X-ray crystallography, molecular dynamics (MD) simulations and cryo-electron microscopy (cryo-EM) are key to understanding proteins involved in disease and how to target them.
However, because advanced Mathematics or Physics modules were not included in my undergraduate training, it was really difficult for me to learn the theoretical aspects of these techniques and how it is applied in practice. I am therefore very grateful for the START project which has given me the opportunity to learn from experts in the field of Structural Biology – experts such as Dr Jeremy Woodward and Prof.Trevor Sewell from the UCT Aaron Klug Centre for Imaging and Analysis. A further challenge throughout my PhD was my limited background in Computational Science. The computer skills I learned from high school were very elementary which meant a particularly steep learning curve when I decided to use MD simulations to answer key research questions.
Studying ACE for the future design of ACE inhibitors
ACE is a dumbbell-shaped protein comprised of two domains (the N- and C-domain) which perform diverse physiological functions: the C-domain is mainly responsible for blood pressure regulation while the N-domain is important for regulating scar tissue formation. The main focus of Prof. Sturrock’s research is to design inhibitors that selectively bind to the N- or C-domain. Selectivity is very important since the side-effects associated with current ACE inhibitors are due to equal inhibition of both domains. At the end of my BSc (Med)(Hons) year, Prof. Sturrock (in collaboration with Prof. Kelly Chibale at UCT) discovered a molecule (33RE) which binds with 1000-times greater affinity to the N-domain than the C-domain of ACE5. N-selective ACE inhibitors are antifibrotic and as such, show potential for the treatment of fibrosis (excessive scar tissue formation). X-ray crystallography was used to study the binding of 33RE to the N-domain but the reason for its selectivity remained a mystery. One limitation of this technique is that it only gives you a static ‘snapshot’ of the protein’s structure while proteins are naturally very dynamic when in solution (as in the body).
For my PhD research, I therefore decided to study ACE using MD simulations. In this technique, the atoms in the crystal structure are allowed to move which can provide more insight into how the drug interacts with the protein. My results were really interesting and showed that subtle amino acid differences between the two domains caused drastic changes in their dynamics and thereby, their affinity for 33RE6.
GCRF START ensures the continuation of postdoctoral research
As a GCRF START postdoc, I am continuing this research in collaboration with Prof. K Ravi Acharya7 at the University of Bath and we have recently discovered that these differences in dynamics also affect the binding and selectivity of ACE inhibitors from different classes89. This has great implications for the future design of ACE inhibitors and emphasizes the importance of using a range of biophysical techniques when studying proteins. The workshops funded by the GCRF START grant has equipped me with valuable skills and I am very excited to discover even more insight into the workings of ACE by applying these skills.
The biggest challenge on my road to becoming a scientist has been financing ten years of tertiary study. Although I was fortunate enough to receive merit and government bursaries to fund my PhD, I am still paying off the student loan from my undergraduate and honours years. Therefore, funding through the GCRF START grant has been invaluable, ensuring the continuation of my postdoctoral research.
Commenting on Lizelle’s achievements and the impact of the GCRF START grant on emerging African scientists like Lizelle, Prof. Ed Sturrock said,
“The GCRF START grant has had a significant impact on Lizelle’s career development, career opportunities and personal growth. Her progress with a very challenging research project and her involvement in other GCRF START activities, such as the START outreach project to uplift the community and promote science through art, bear testament to this. I have been enormously impressed by what Lizelle has achieved as a START postdoctoral research fellow in a relatively short period of time.”
Read more about the UN’s Sustainable Development Goal 3 for Health and Wellbeing here.
I am very grateful to Mrs Sylva L. U. Schwager (Chief Scientific Officer in Prof. Sturrock’s laboratory at the University of Cape Town) for her guidance and assistance with key experiments during my postgraduate and postdoctoral years.
Cozier, G.E., Lubbe, L.*, Sturrock, E.D., Acharya, K.R. ACE-domain selectivity extends beyond direct interacting residues at the active site. Biochem J 477 (7), 1241–1259 (2020) https://doi.org/10.1042/BCJ20200060
Sturrock, E.D., Lubbe, L., Cozier, G.E., Schwager, S.L.U., Arowolo, A.T., Arendse, L.B., Belcher, E., Acharya, K.R. Structural basis for the C-domain-selective angiotensin-converting enzyme inhibition by bradykinin-potentiating peptide b (BPPb). Biochem J 476 (10), 1553–1570 (2019) https://doi.org/10.1042/BCJ20190290
“The GCRF START grant has initiated a beautiful story and this story involves developing African scientists, especially in terms of Synchrotron Radiation Technology and Research. We hope to continue this highly fruitful collaboration for many years to come.”
Dr Ikechukwu Anthony Achilonu, Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand
I love teaching and research, especially contributing towards human development through innovative research in medicine and biology. My research focuses on the Biochemistry and Structural Biology of druggable proteins of human Neglected Tropical Diseases (NTD’s) and ESKAPE pathogens (Healthcare Acquired Infections) at the University of the Witwatersrand’s Protein Structure-Function Research Unit (PSFRU). I owe my motivation for biochemistry to very good teachers and mentors from an early point in my education.
I was educated to undergraduate level in biochemistry at Nigeria’s Abia State University, Uturu, Abia State and as an undergraduate, found pleasure in being taught by biochemistry lecturers who were able to ‘self-de-elevate’ and inspire us. These teachers were easy to have rapport with and I was able to extract as much as they could offer, both as my teachers, as well as my mentors and motivators. I remember Dr Okechukwu Ukairo, a young and admirable biochemistry lecturer who taught us carbohydrate metabolism and bioenergetics. His persona as a biochemistry lecturer and researcher enabled him to de-mystify what was a difficult course in biochemistry by being down to earth, but not to be trampled upon!
Subsequently, I spent four years in Lesotho as an educator, teaching in secondary schools after briefly working as an analytical chemist at Lesotho Pharmaceuticals in Mafeteng. My desire to do my Master’s in Biochemistry was fulfilled, however, at the University of KwaZulu-Natal in Durban, South Africa, where I gained my PhD in 2008. Working with Prof Heini Dirr at Wits University (March 2009) strengthened my aspiration in Structural Biology and three years later, I joined The University of the Witwatersrand. Currently, I am a Senior Researcher and the Interim South African Research Chair (SARChI) in Protein Biochemistry and Structural Biology.
When I look back at my career journey so far, it was the experience of having inspiring teachers and mentors that stayed with me to the present day and drives my vision as head of my group in teaching, supervising and mentoring the students on my watch. Therefore, the GCRF START grant with its emphasis on equipping and mentoring the next generation of scientists in Africa to tackle local and global challenges, means everything to me, especially in terms of structural biology.
African scientists have a critical role to play in the search to solve Africa’s challenges
“My vision is to see young people rise-up and flourish in the sciences on the African continent and apply the African, UK and global perspectives we share in the GCRF START network to the global challenges we face.”– Dr Ikechukwu Anthony Achilonu, Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand
With the START grant I believe we can create a new narrative of excellence in African science and structural biology and fulfil our vision to equip our students in the latest techniques to solve our continent’s health, energy and socio-economic challenges. For example, at the PSRU, we have many gifted post-docs and undergraduates with the potential to go far and make a positive difference on our continent and beyond. I supervise 12 students (four PhD and seven MSc. students, and one Post-Doctoral Fellow), some of whom already benefit from the exposure to state-of-the-art synchrotron techniques at the UK’s national synchrotron – Diamond Light Source (Diamond) – as a result of the GCRF START grant. Often from previously disadvantaged backgrounds and female, these students have attended START funded workshops, have collected data remotely, and are being trained by scientists from the Diamond beamlines. They would love to one day visit Diamond to see a synchrotron for themselves and want to develop careers in structural biology and biochemistry.
Our dream is that each university in South Africa and beyond our borders will have new generation structural biology, synchrotron and drug discovery techniques taking place as a matter of course. In South Africa, our vision is to include lesser known universities like Venda, Fort Hare, and Johannesburg ensuring that those previously unable to access to opportunities will be able to do so. Already, in just over two years, the START network has grown in South Africa to encompass a wide range of university groups/hubs covering a broad variety of research disciplines to address challenges across Africa, as well as globally.
Take viruses like COVID-19, for example, we have every potential to be able to produce the targeted, appropriate vaccines and drugs needed for our unique situations. Instead of researchers from Europe and America coming to us to collect samples to take over to Europe/America to do their studies, we could be on an equal footing and able to do every stage of the research right here in Africa so that we are well prepared for outbreaks when they occur.
In terms of our journey at the PSFRU, the GCRF START grant and Diamond Light Source came at the right time for our group, and for me personally. When I got involved with START in 2018, most of my protein crystal structures were solved in-house using a home-source XRD Wits University commissioned in 2008. However, over the years, the life of the machine started depreciating and we had to look for an alternative light source. Prof. Yasien Sayed, Director of the PSFRU, was contacted by START Co-I, Prof. Trevor Sewell, from the University of Cape Town to champion the University of the Witwatersrand’s Structural Biology collaboration with Diamond as part of the South African broader collaboration with the facility, and because Prof. Sayed and I work in the same research unit, he involved my research in his application.
The common denominator is science!
“I know some people say that the priorities in Africa are all about hunger, and that doing scientific research is not a priority but if you look at all the challenges here, the common denominator is science!”– Dr Ikechukwu Anthony Achilonu, Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand
We can’t do without the science and the latest scientific equipment in terms of tackling Africa’s sustainable development goals. Take hunger and the goal of food security, for example. We need drought resistant crops and pest resistance; we need clean water sources and uncontaminated land; we need disease solutions for the animals and a healthy variety of nutritional and affordable crops; we need people who are sufficiently healthy to grow the food, distribute, manufacture and sell it. Indeed, some of the pathogens I am working on right now, such as Schistosomiasis (Bilharzia), affect a prime source of food security on our continent – cattle. The poultry industry is another example where multiple pathogens kill the poultry which people rely on for food. Therefore, investing in science in Africa is imperative for the health of our continent and the world.
However, sustainable sources of funding are needed to conduct world class science. Even in terms of small things like shipping samples, it costs over 3500 Rand (£160.00) each time we ship our protein crystals to and from Diamond. This would be prohibitive for many science groups if it were not for grants like GCRF START. The fact that START grant enables us to do the experiments remotely at Diamond, means we can save money – we don’t have to fly abroad to conduct our experiments and we speak the same language so there are no ‘lost in translation’ issues!
To demonstrate some of the diverse and world class science research we do at the PSFRU I have outlined three examples below, which benefit from the GCRF START grant.
Exploring language and cognition: untangling the neuromolecular networks in the brain
Dr Sylvia Fanucchi’s research looks in detail at a particular node of interaction that is implicated in Autism. This involves investigating the FOXP family of transcription factors which are associated with language and cognition. Her studies aim at untangling the neuromolecular networks in the brain by identifying the nodes of interactions associated with these proteins. In order to do this, Dr Fanucchi explores protein-protein interactions and protein-nucleic acid interactions and how they influence each other in these large neuromolecular complexes. Through the GCRF START grant using the Diamond synchrotron, Dr Fanucchi can investigate the structures of both protein-DNA and protein-protein complexes. This information is highly valuable in dissecting the interactions within these neuromolecular complexes at atomic resolution and is critical to answering the questions posed by Dr Fanucchi in her research.
New insights into the South African HIV-1 subtype C protease
Another example of success is Prof. Yasien Sayed’s research on the HIV C protease1 – the strain of the HIV virus we have in South Africa, whereby Prof Sayed and his team are the first to solve the type C protease at unparalleled resolution. This is a significant success (pending publication) which has been made possible with access synchrotron techniques at Diamond with the GCRF START grant2. This paves the way to repurpose AntiRetrovirals (ARV’s) that are tailor-made for the type of HIV we have here in South Africa so that in years to come, HIV prevention and treatment can be far more effective than they are now. Currently, the ARV’s employed here in South Africa are not tailored specifically for our strain of the HIV virus, which means that the side effects are more than they should be (leading to problems with ARV adherence) and drug resistance.
Schistosomiasis/Bilharzia – solving the 3D structure of the Schistosoma japonicumGlutathione S-transferase (GST) protein
“Access to facilities at Diamond has enabled young and emerging researchers, such as Dr. Achilonu in my Unit to realise their potential by publishing their research in internationally peer-reviewed journals.” –
Prof. Yasien Sayed, Director of the Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand, South Africa
There are several milestones yet to be reached but my journey with the GCRF START grant is already yielding fruitful outcomes for Africa. My publication3 titled “Molecular basis of inhibition of Schistosoma japonicum glutathione transferase by ellagic acid: insights into biophysical and structural studies” is one of those milestones achieved over the past three years. Using I03 & I04 beamlines at Diamond, we were recently able to solve the 3D structure of the Schistosoma japonicum GST protein atan unprecedented resolution of 1.53 Å- amongst the highest resolution in the current global protein database for this enzyme!
The resulting publication emphasises the need to exploit the unique structural diversity between Schistosoma GST and other human GSTs for a rational approach to design new generation anthelminthics. Without the high-resolution structure of the Schistosoma GST-in-complex with the potential natural product (Ellagic Acid) – which we aim to study for the design of new anti-Schistosoma drugs – it would have been difficult understanding several empirical observations made in our research. Achieving these results means we can now progress further to find effective drug targets, something only possible to the level we need using synchrotron techniques. I am very grateful to the GCRF START grant and Diamond for this opportunity.
Our vision to collaborate with groups in other African countries is also progressing. One such group is a medical research institute working on Schistosoma in Kenya with whom we hope to have a collaboration up and running by early next year. Now that we have new insights afforded by the solved structure of the Schistosoma japonicum GST protein, we need to know that the drug target we are investigating is active against an entire parasite – either as a parasite on its own or in an animal. A collaboration with the Kenyan group offers exciting opportunities to explore this. I also have students from Nigeria, Zimbabwe and Namibia who will be joining us next year; and one from India, therefore our group is truly pushing the boundaries geographically as well as scientifically!
Towards an African Light Source
For many, the ultimate vision is having an African Synchrotron Light Source on the African continent. However, it may take years before this is possible and therefore, in the meantime, the START grant enables us to move closer to fulfilling our vision to inspire creative and collaborative scientific research and equip the next generation of scientists in structural biology (and energy materials) to use synchrotron equipment and techniques. I pray and hope that GCRF START and Diamond continue this incredible journey with us, long into the future.
Read more here about the UN’s Sustainable Development Goals.
More about Dr Achilonu
Dr Ikechukwu Anthony Achilonu is Senior Researcher and the Interim South African Research Chair (NRF/SARChI) in Protein Biochemistry and Structural Biology at the Protein Structure-Function Research Unit (PSFRU), School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand in South Africa.