Expanding the pool of African research talent to tackle disease challenges – world class technology, expertise, and peer-training with the GCRF START grant

“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.

GCRF START PDRA, Blake Balcomb, at Stellenbosch University, South Africa. The image on screen behind Blake is of a flavoprotein. Flavoproteins play a major role in a wide array of biological processes.
Photo credit: Blake Balcomb. ©Diamond Light Source

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.

GCRF START PDRA, Blake Balcomb from Stellenbosch University, South Africa, sharing some of his findings with the MX Group’s Life Sciences Seminar at the UK’s national synchrotron.
Photo credit: Blake Balcomb. ©Diamond Light Source

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.  

GCRF START PDRA, Blake Balcomb in the laboratory at Stellenbosch University in South Africa, with Master’s student, Karli Bothma, discussing Karli’s protein expression results.
Photo credit: Blake Balcomb. ©Diamond Light Source

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.

GCRF START PDRAs, Blake Balcomb and Anton Hamann inspecting bacterial transformation results in the laboratory at Stellenbosch University in South Africa. Photo credit: Blake Balcomb. ©Diamond Light Source

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[1]. 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.”

Nicholas Herbert collecting data on one of his own crystals via remote access to the UK’s national synchrotron, Diamond Light Source, conducted from Stellenbosch University in South Africa.
Photo credit: Blake Balcomb. ©Diamond Light Source

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.


[1] Int J Infect Dis. 2018 Aug; 73:78-84. doi: 10.1016/j.ijid.2018.06.004

Did you know that globally only 30% of science researchers are female?

And why collaborating with young female scientists in Africa is reaping great results.

Timed to coincide with UN International Day of Women and Girls in Science on 11 Feb, and to inspire more female students to study and work in science, the GCRF START grant has announced the results of its three year project launched in March 2019.  To date it has directly collaborated with nearly 50 young African research students and given access to almost 100 synchrotron beamline sessions.  Over half of START’s students are female scientists who are demonstrably changing perceptions and increasing the possibilities for women choosing long term STEM research careers.

“Globally UNESCO figures show that only 30% of researchers are female and they occupy only 20% of STEM leadership positions. These figures are even lower in many countries in Africa underlining how important it is to challenge women’s under-representation. Young female African scientists are vital both for their research and as role models and mentors for the next generation.  So we are really delighted to see many of the young women we collaborate with through the START grant, making great strides and achieving some incredible results in the fields of structural biology and energy materials

Prof. Chris Nicklin, Science Group Leader and Principal Investigator (PI) in the GCRF START (Synchrotron Techniques for African Research and Technology) grant programme.
Michelle Nyoni, University of the Witwatersrand & Chinhoyi University of Technology (CUT). Michelle Nyoni, part-time PhD student at the University of the Witwatersrand, South Africa, and Chemistry lecturer at the Chinhoyi University of Technology (CUT), Zimbabwe. Michelle collaborates with the GCRF START grant in the field of energy materials. ©Diamond Light Source

GCRF START  is an innovative collaboration between Diamond Light Source,  the UK’s national synchrotron,  and higher education and research partners in the UK and Africa. It is funded by the Science and Technology Facilities Council under the UK government Global Challenge Research Fund programme.  It is enabling and inspiring researchers from this, and the next generation of Africans to choose careers in science and find African and joint UK-African solutions to some of the world’s most pressing health and environmental challenges.  A key goal is to challenge the under-representation of women in science by providing access to world-class scientific facilities, funding, training, mentoring, and unique international collaborations.  Great results have been achieved in a relatively short space of time because START scientists get access to specialist technologies and facilities not available on the African continent – like beamtime on the Diamond synchrotron.

One indicator of the success of the programme is how the tiny community of structural biologists in Africa has grown across South Africa including a whole new generation of women. Similarly, in energy materials, the gender factor has traditionally been a barrier, so having young women entering materials science is great progress. Additionally, all these women participate in outreach and act as role models to inspire girls to choose STEM careers. Female START successes include:

Priscilla Masamba  has solved the partial structure of a protein from Schistosoma mansoni, a parasite responsible for the debilitating disease Schistosomiasis (Bilharzia) which is endemic in more than 78 countries, with an estimated 4 million people infected in South Africa alone. Her work will contribute to drug discovery efforts and is notable because she was the first student from the University of Zululand, South Africa, to use the Diamond synchrotron, which she did remotely from a lab in South Africa learning many scientific techniques for the first time;                                 

Thandeka Moyo  is part of a leading South African team working on HIV/AIDS vaccine research and is currently researching Covid-19; Originally from Zimbabwe, Thandeka mentors early career female scientists and is a role model for school children;                                                                                             

Gugulethu Nkala is investigating new generation renewable energy storage systems in South Africa to help close the energy poverty gap; she is active in inspiring girls into STEM;

Lizelle Lubbe is a GCRF START grant-funded Postdoctoral Research Fellow in Structural Biology (a scarce skill in Africa). Lizelle is one of only a handful of scientists in Africa as a whole trained in single particle cryo-EM –  a cutting-edge technique for determining the structure of proteins;

Michelle Nyoni  is studying energy materials to improve the performance of Lithium-ion batteries for portable electronics and renewable energy sources to make them affordable and improve their environmental footprint to tackle climate change. Michelle is also a chemistry lecturer in Zimbabwe.

“The GCRF START grant has been a game-changer for young African scientists, particularly from under-represented groups such as female, and black scientists, enabling them to enter the fields of Structural Biology and Energy Materials and thrive.”

GCRF START Co-Investigator, Prof. Edward D. Sturrock from the University of Cape Town, South Africa.
GCRF START grant-funded Postdoctoral Research Fellow, Dr Lizelle Lubbe (L), with fellow scientists, Melissa Marx (R)& Andani Mulelu at the University of Cape Town, South Africa.
Photo Credit Rebekka Stredwick. ©Diamond Light Source

One young scientist working with START, Gugulethu Nkala, is an Energy Materials PhD student from South Africa. The eldest of three daughters and first in her family to go to university, she remarks; “Seeing a black girl in science, makes girls 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.”

Access to inclusive quality education and lifelong learning opportunities is a distant dream for many young people across Africa, especially women. Few have the opportunity to finish school, let alone reach university to study world-class science, be mentored by experts or continue to postdoctoral studies. This can be due to lack of access to resources at home institutions, insufficient grant writing experience, lack of mentors or supervisors, inadequacy of facilities, and poor postdoctoral pay.

“It is important to support and mentor young women in science especially since women are largely under-represented, particularly in the case of the physical sciences, the field in which we work. I found that having access to synchrotrons and also building international collaborations through the GCRF START grant programme has not only allowed the young women that I work with to gain better skills but they also grow in confidence about their abilities” 

Professor Caren Billing, Energy Materials Research Group Co-Principal Investigator (Co-PI), Lecturer and Associate Professor in the School of Chemistry at the University of the Witwatersrand, South Africa.
Gugulethu Nkala, energy materials PhD student at the University of the Witwatersrand, South Africa, on a workshop tour of UK’s national synchrotron, Diamond Light Source (Diamond), in March 2020. Here Gugu is looking at the large red magnets that are part of the linear accelerator at Diamond on a visit to the Diamond synchrotron funded by the GCRF START grant.  The electron beams travel through the linear accelerator and are used to investigate the samples provided by the scientists for their experiments. Photo credit: Gugulethu Nkala. ©Diamond Light Source

The GCRF START grant supports young scientists working on key Climate, Energy, Health, and Education challenges in line with the UN’s Sustainable Development Goalsby building partnerships between world leading scientists in Africa and the UK and enabling them to work together on research using synchrotron science. The project focuses on developing and characterising new energy materials, for example in the development of solar cells or improving energy efficiency through novel catalysts, and structural biology to understand diseases and develop drug targets for better treatments and potential vaccines.  The START programme is grant-funded through the UK’s Global Challenges Research Fund (GCRF) and delivered by UK Research and Innovation (UKRI) through the Science and Technology Facilities Council (STFC) and the UK’s national synchrotron facility, Diamond Light Source.

 “Science is a collaborative discipline. Yet science is being held back by a gender gap. Girls and boys perform equally well in science and mathematics – but only a fraction of female students in higher education choose to study sciences. To rise to the challenges of the 21st century, we need to harness our full potential. That requires dismantling gender stereotypes. It means supporting the careers of women scientists and researchers.” United Nations, Secretary General, Antonio Guterras, United Nations International Day of Women and Girls in Science – 11 February

Dr Priscilla Masamba, Postdoctoral Researcher in structural biology at the University of Johannesburg, South Africa (previously PhD student at the University of Zululand). Here she is in the laboratory at the University of Cape Town where she conducts some of her experiments. Photo credit: Rebekka Stredwick. ©Diamond Light Source
Thandeka Moyo, GCRF START Postdoctoral Research Fellow at South Africa’s National Institute for Communicable Diseases ((NICD) and affiliated to the University of the Witwatersrand, South Africa.
Photo credit: Thandeka Moyo. ©Diamond Light Source
GCRF START Postdoctoral Research Fellow, Dr Lizelle Lubbe (L) & MSc. Student Melissa Marx (R) from the University of Cape Town next to the Titan Krios III, at the UK’s national synchrotron, Diamond Light Source where they conducted experiments in structural biology. Photo credit: Dr Jeremy Woodward. ©Diamond Light Source

Breaking barriers and aiming high! An African woman in Energy Materials Science – Gugulethu Nkala’s story

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[1], Prof Caren Billing[2] and Dr Roy Forbes, her particular interest is: ‘The Use of Fused Bimetal Phosphate-based Ceramics for Solid-State Electrolyte Applications’[3], 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).

Energy Materials scientist, Gugulethu Nkala, PhD student at the University of the Witwatersrand, South Africa. Photo credit: Gugulethu Nkala. ©Diamond Light Source

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.  

Energy materials PhD student, Gugulethu Nkala, on a workshop tour of UK’s national synchrotron, Diamond Light Source (Diamond), in March 2020. Here Gugu is looking at the large red magnets that are part of the linear accelerator at Diamond. The electron beams travel through the linear accelerator and are used to investigate the samples provided by the scientists for their experiments. Photo credit: Gugulethu Nkala. ©Diamond Light Source

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[4]. Approximately 80% of South Africa’s electricity relies on coal, with the resulting environmental challenges that this brings[5]. 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[6].

Commercial batteries use an organic liquid as an electrolyte and these organics compromise the safety of the battery[7]. Increasingly, alternative electrolyte materials have received great attention, more specifically solid-state electrolytes[8]. 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[9].

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.”

Energy materials PhD student, Gugulethu Nkala, at a University of the Witwatersrand’s science outreach event in South Africa.
Photo credit: Gugulethu Nkala. ©Diamond Light Source

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!”

Energy materials PhD student, Gugulethu Nkala, from the University of the Witwatersrand, South Africa, on a visit to the UK’s national synchrotron Diamond Light Source.
Photo credit: Gugulethu Nkala. ©Diamond Light Source

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.”

Energy Materials PhD student, Gugulethu Nkala, with the GCRF START banner at the University of the Witwatersrand, South Africa. Photo credit: Gugulethu Nkala. ©Diamond Light Source

[1] 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.

[2] Prof Caren Billing is Associate Professor in the School of Chemistry at the University of the Witwatersrand, South Africa

[3] 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.

[4] Eberhard, A., Leigland, J. and Kolker, J., 2014. South Africa’s Renewable Energy IPP Procurement Program. World Bank Publications. (https://ppp.worldbank.org/public-private-partnership/library/south-africa-s-renewable-energy-ipp-procurement-program-success-factors-and-lessons-0)

Banks, D. and Schäffler, J., 2005. The potential contribution of renewable energy in South Africa. Sustainable Energy & Climate Change Project (SECCP). ( https://www.ee.co.za/wp-content/uploads/legacy/Gener%201.pdf )

Fluri, T.P., 2009. The potential of concentrating solar power in South Africa. Energy Policy37(12),pp.5075-5080. (https://econpapers.repec.org/article/eeeenepol/v_3a37_3ay_3a2009_3ai_3a12_3ap_3a5075-5080.htm)

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 Energy137, pp.511-536.

[5] 82.6% in 2018 (South African Energy Sector Report 2018) http://www.energy.gov.za/files/media/explained/2018-South-African-Energy-Sector-Report.pdf

[6] Kuwano, J., Sato, N., Kato, M. and Takano, K., 1994. Ionic conductivity of LiM2 (PO4) 3 (M= Ti, Zr, Hf) and related compositions. Solid State Ionics70, pp.332-336.

Pegels, A., 2010. Renewable energy in South Africa: Potentials, barriers and options for support. Energy policy38(9), pp.4945-4954.

[7] Takada, K., 2013. Progress and prospective of solid-state lithium batteries. Acta Materialia61(3), pp.759-770.

[8] Quartarone, E. and Mustarelli, P., 2011. Electrolytes for solid-state lithium rechargeable batteries: recent advances and perspectives. Chemical Society Reviews40(5), pp.2525-2540.

[9] Kuwano, J., Sato, N., Kato, M. and Takano, K., 1994. Ionic conductivity of LiM2 (PO4) 3 (M= Ti, Zr, Hf) and related compositions. Solid State Ionics70, pp.332-336.

In the spirit of Ubuntu: Addressing global challenges through community-led Sci-Art

We are delighted to announce that our exciting Sci-Art collaboration with The Keiskamma Trust in South Africa is well underway! In the spirit of Ubuntu [1], funded by the GCRF START grant, the collaboration involves a unique series of tapestries inspired and created by community-based artists and crafters from the Trust’s flagship Keiskamma Art Project located in South Africa’s Eastern Cape. The artwork is based on concepts provided by scientists in the UK and Africa working on GCRF START-related Energy Materials and Structural Biology themes. The aim of the collaboration is to stimulate shared learning and dialogue on solutions to local and global challenges in line with Sustainable Development Goals: from alternative energy solutions to tackle pollution and climate change, and biotechnology for food security, to improved health outcomes through novel drug discovery and design.

Embroidery crafters from The Keiskamma Trust’s flagship Art Project sewing tapestries depicting
GCRF START-related research by scientists in the UK and Africa.
Photo credit: Pippa Hetherington, The Keiskamma Trust. Copyright: The Keiskamma Trust

The Keiskamma Trust is a small, Non-Profit Organisation (NPO) in South Africa’s Eastern Cape dedicated to addressing HIV/AIDS and poverty holistically through health, art, music and education initiatives. With unemployment levels in the region’s rural areas up to 90%, and water shortages, poor nutrition, lack of electricity, and diseases like HIV/AIDS, Tuberculosis (TB) and diabetes highly prevalent, hardship is an everyday experience for the remote communities the Trust serves. The artists and crafters creating the tapestries hail from the villages of Hamburg, Bodiam and Bell in the surrounding communities.  Overcoming many challenges including months of Covid19 lockdown, they have already completed several panels, including one large panel and a series of smaller ones, with more panels nearing completion.

While the large ‘Our Vision for Africa’ panel gives vibrant expression to a community-led vision of a future with clean air and access to sustainable energy and good health, the smaller panels intricately depict a host of specific research topics. These range from explaining the purpose of the UK’s national Diamond Light Source synchrotron (Diamond), which lies at the heart of the GCRF START grant, to research on structures of proteins for novel HIV, blood-pressure and anti-fungal infection drug treatments, studies exploring organic solar energy materials, and themes on the role of catalysis, which underpins food production, generation of clean energy, and maintenance of clean water and air.

The ‘Our Vision for Africa’ large panel designed by Siyabonga Maswana and Sanela Maxengana, artists of the Keiskamma Art Project. This panel depicts the artists’ vision for the future of their village, which is what the GCRF START grant is all about: access to sustainable development goals of good health, sustainable energy, and a clean environment. Each element on the panel relates to different aspects of research from catalysis and energy materials, to drug discovery and biotechnology. Photo credit: Jeremy Woodward. Copyright: University of Cape Town on behalf of a collaborative project with the Synchrotron Techniques for African Research and Technology (START) in the United Kingdom funded by the Global Challenges Research Fund (GCRF) START grant. ‘Our Vision for Africa’, 2020, Keiskamma Art Project. Embroidered by Nomgcobo Nompunga and Asanda Nompunga.

Artwork commissions like the SciArt collaboration bring much needed employment and income generation opportunities to the staff employed by the Keiskamma Art Project. Such commissions can also provide a platform for empowering skills development and learning, as Cebo Mvubu, theproduction managerat the Keiskamma Art Project, explains, “Here in South Africa the unemployment is too high and now even more with the Covid19 crisis”, says Cebo. “Commissions like the GCRF START Sci-Art project help many people from our villages, directly and indirectly. The income feeds our families and helps send our kids to school, and even if just one person is working on a project like the START commission, this helps support more than 5-8 people in their extended family. We also benefit from the skills we learn when doing these commissions and the publicity the project gets.”

The villages served by The Keiskamma Trust are located in a remote, rural part of South Africa’s Eastern Cape.
Photo credit: Pippa Hetherington, copyright: The Keiskamma Trust.

There are many stories of hope among the crafters and artists at the Keiskamma Art Project, not least those reflecting the strength of the women in the region – described as ‘elabafazi’ in the local Xhosa language. One such story is from a crafter who is the sole breadwinner in her family, despite suffering from chronic health conditions, she alone supports her younger sisters, brothers and her daughter who are all unemployed.

“I have a big challenge because I am a single mother and I have to look after the kids at home,” the crafter from the Keiskamma Art Project explains. “I am not 100% health-wise so it is a big thing to feed everyone, enable them to go to school, and to keep a home. But since the year 2000, when I was accepted by the The Keiskamma Trust, I have employment which supports my family. I have learnt sewing, drawing, embroidery, felt-making, screen printing, pottery, and painting. It is a big opportunity to be the part of START’s Sci-Art project.”

A crafter from the Keiskamma Art Project sewing a tapestry panel for the GCRF START grant’s Sci-Art project depicting research on blood pressure. Photo credit: Cebo Mvubu, The Keiskamma Trust. Copyright: The Keiskamma Trust

There is a strong desire amongst the artists and embroidery crafters working on START’s SciArt commission for dialogue with the scientists in order to learn more about the concepts behind their creations, especially what the science could mean for their families and communities, “We want to learn from each other and from the scientists as we see this as a collaboration,” says Cebo. “It is one of the things we would love to know: what the scientists do. For example, we would like to know more about solar energy. We need new energy options here because we have little electricity and we often have load-shedding. But we do have lots of sunshine! We also hear that the scientists want to learn from us too. We would like to show them how we do this artwork.”

Cebo Mvubu, Production Manager at The Keiskamma Trust’s flagship Keiskamma Art Project. Photo credit: The Keiskamma Trust. Copyright: Diamond Light Source

“There is a hunger here for greater connectivity. We can fashion a bridge from science to art through the interpretation of research concepts into embroidery, but it would mean so much to us if the science itself could touch our communities,” says Michaela Howse, curator and manager at the Trust’s Keiskamma Art Project. “It is rare that science being done in metropolitan centres, or internationally, reaches our villages and it is very exciting to work on concepts that seem to come from another world,” explains Michaela. “Dialogue between artists in our unique contexts, and the GCRF START scientists in theirs, may enrich both parties. Perhaps the applications of the research might one day grow to directly impact the needs of communities whose main concerns remain improved health, education opportunities, as well as dignity in life above all things.”

To encourage dialogue, the artists and embroidery crafters have recently written a letter to the scientists collaborating with START asking them to share how the concepts provided by the researchers could impact their villages. In the letter they ask: “Can your work educate us or help us in understanding energy, electricity, water, disease, better health and better lives? We would love to hear from you.”

The scientists are currently responding with letters of their own, explaining what the science might mean for improving everyday lives. In one such letter, scientists collaborating with START from the Biocatalysis and Structural Biology Research Group at the University of the Free State, in South Africa, respond by citing the inspiration behind their research to find new anti-fungal compounds which can be used in the health and agricultural sectors, “Dear Keiskamma community,” the letter states. “Thank you for your letter – both your commitment to your art and your determination in difficult circumstances inspire us to work hard on our research and make a difference in people’s lives.”

“I find it motivating to see the artists represent their vision of a better future through their artwork and I hope the science that I do has a positive impact on the world,” says GCRF START Co-Investigator, Dr Jeremy Woodward, who is the Principal Investigator in the Structural Biology Research Unit at the University of Cape Town. “These artworks show what the GRCF START grant is all about: using the most sophisticated technology in the world to enable Africans to solve African and global problems. I particularly hope that young people see these artworks and this plants the seed so that people see that science can be done anywhere in the world, by anyone.”

“It has been a great joy to see our science come to life through the eyes of the Keiskamma artists and I am very excited about the project’s potential to uplift communities in Africa,” says GCRF START Postdoctoral Research Assistant, Dr Lizelle Lubbe, from the University of Cape Town. “I hope this collaboration will break down barriers to science and inspire future generations of researchers and innovators, as well as stimulate dialogue with the communities impacted by the challenges that people in Africa and around the world face.”

The ‘Angiotensin Converting Enzyme’ panel. A tapestry designed by Cebo Mvubu of the Keiskamma Art Project based on research by Prof. Ed Sturrock (GCRF START Co-I) and GCRF START Postdoctoral Research Assistant, Dr Lizelle Lubbe, from the University of Cape Town, South Africa. The panel shows a snake wriggling through a blood vessel that has become affected by a build-up of fats, cholesterol and calcium (atherosclerosis). High blood pressure is a major cause of atherosclerosis and can lead to heart attacks and strokes. Certain snake venoms contain compounds that, when injected, cause their prey to lose consciousness from a drop in blood pressure. The venom of the Brazilian viper inhibits angiotensin converting enzymes and forms the basis for medicines that are used to lower blood pressure and treat heart disease.

Photo credit: Jeremy Woodward. Copyright: University of Cape Town on behalf of a collaborative project with the Synchrotron Techniques for African Research and Technology (START) in the United Kingdom, funded by the Global Challenges Research Fund (GCRF) START grant. ‘Angiotensin Converting Enzyme’, 2020, Keiskamma Art Project.

Embroidered by Nosiphiwo Mangwane.

The ‘Flexible Solar Cells’ panel. A Solar Energy tapestry designed by artist Nozeti Makubalo from the Keiskamma Art Project. The panel design is based on a collaborative concept provided by Prof. Moritz Riede (GCRF START Co-I) and Postdoctoral Research Assistant, Dr Pascal Kaienburg, from the University of Oxford, and Prof. Chris Nicklin (GCRF START PI) and Postdoctoral Research Associate, Dr Thomas Derrien, from the UK’s national synchrotron, Diamond Light Source (Diamond), all of whom work closely together on Solar Energy research. The materials being studied can be used to make solar cells which harness the sun as a source of energy. The research looks at how to improve the efficiency of materials in ‘organic semiconductors’ to make them commercially viable. These are more lightweight, flexible, environmentally friendly, and easier to deploy in rural environments than heavy, stiff panels of silicon-based solar cells.  The data obtained tells us how these materials organise themselves on devices, which can affect how well the solar cells work.

Photo credit: Jeremy Woodward. Copyright: University of Cape Town on behalf of a collaborative project with Synchrotron Techniques for African Research and Technology (START) in the United Kingdom funded by the Global Challenges Research Fund (GCRF) START grant. ‘Flexible Solar Cells’, 2020, Keiskamma Art Project.

Embroidered by Nozeti Makubalo.

The ‘Aspergillosis’ panel. A tapestry designed by artist Siyabonga Maswana from the Keiskamma Art Project based on a concept provided by Dr Diederik Opperman (GCRF START Co-I) from the University of the Free State’s Biocatalysis and Structural Biology Research Group in South Africa. Opportunistic fungal pathogens (agents) invade vulnerable individuals, such as immune-compromised patients, and cause life-threatening health conditions (mucoses). Anti-fungal agents are used to combat mycoses but current therapies often suffer from toxicity, as well as emerging anti-fungal resistance, prompting the search for alternative medicinal drug targets. The panel depicts invasive aspergillosis, an infection caused by a type of fungus, growing on the lungs. The bright light of the UK’s synchrotron, Diamond Light Source, and a technique called X-ray crystallography are used to examine the structures of fungal redox enzymes (special types of proteins) as novel anti-fungal drug targets.

Photo credit: Jeremy Woodward. Copyright: University of Cape Town on behalf of a collaborative project with Synchrotron Techniques for African Research and Technology (START) in the United Kingdom funded by the Global Challenges Research Fund (GCRF) START grant. ‘Aspergillosis, 2020, Keiskamma Art Project.

Embroidered by Nomakhaya Dada.

‘Chemistry from Plants’ panel. A tapestry designed by artist Siyabonga Maswana from the Keiskamma Art Project based on a concept provided by Dr Jeremy Woodward (GCRF START Co-I) from the University of Cape Town’s Structural Biology Research Unit in South Africa. Plants produce a variety of chemical compounds to defend themselves from being eaten and these poisons need to be detoxified by the plant when not needed. The panel depicts a small weed – Red Shepherd’s Purse – which repels insects by producing poisonous compounds called nitriles. These are broken down by three different enzymes, each converting nitriles of a different size. How these enzymes worked was a mystery until now because we couldn’t visualise them. Normally, enzymes arrange themselves into crystals that allow us to determine the positions of every atom but in this case it wasn’t possible because of their pentameric shape, as shown on the panel by pentagons that do not assemble into a space-filling pattern. Now, using the UK’s Diamond Light Source Synchrotron (Diamond) and the Titan Krios III (beamline M06) at Diamond’s Electron Bio-Imaging Centre (eBIC), Dr Woodward has been able to image these enzymes for the first time, paving the way to design new enzymes for a range of ‘eco-friendly’ biotechnology applications, from cleaning up toxins in contaminated land to improving crop types and yields, and helping design medicines with fewer side effects.  

Photo credit: Jeremy Woodward. Copyright: University of Cape Town on behalf of a collaborative project with Synchrotron Techniques for African Research and Technology (START) in the United Kingdom funded by the Global Challenges Research Fund (GCRF) START grant. ‘Chemistry from plants’, 2020, Keiskamma Art Project.

Embroidered by Thembisa Gusha.

Typical village scene in the rural communities of the Eastern Cape of South Africa.
Photo credit: Cebo Mvubu. Copyright: The Keiskamma Trust

Tapestry topics

Catalytic CO2 conversion to methanol for producing  renewable and sustainable fuels; new compounds for controlling blood-pressure; enzymology for solutions to food security; anti-fungal drug targets for life-threatening fungal infections (mycoses); the structure of the South African HIV-1 Subtype C Protease for insights into a possible HIV vaccine/treatments; research into antibiotic-resistant strains of  the bacteria Staphylococcus aureus;  improving efficiency of solar cell materials; finding solutions to diseases like Malaria, and research on Rotaviruses which are the most common cause of diarrheal disease.

GCRF START SciArt project collaborating institutions

South Africa: University of the Witwatersrand; University of Cape Town; Stellenbosch University; University of the Free State; North-West University; Aim Shams University; University of Limpopo; University of Pretoria; National University of Lesotho; National Institute of Communicable Diseases (NICD).

United Kingdom: Diamond Light Source; University of Oxford; University of Southampton; University of Cardiff; University of Sheffield.

More about The Keiskamma Trust

The Keiskamma Trust uses art and heritage/tourism to alleviate long-standing poverty and unemployment in the communities of Hamburg, Bodiam and Bell in the Eastern Cape of South Africa. Founded in 2000 by the local Xhosa community with the help of the Trust’s first director, artist and doctor –  Dr Carol Hofmeyr – the Trust’s community driven and inspired Keiskamma Art Project works to develop creative skills to empower mainly women and young members of the community. It does this through turning inherent talents into sustainable income-generating activities, showcasing the local culture and heritage, and aiding the archiving of the Eastern Cape rural collective memory and preservation of oral history. Read more here about The Keiskamma Trust. Related articles: The Keiskamma Art Project: Restoring Hope and Livelihoods:https://www.tandfonline.com/doi/abs/10.1080/00043389.2017.1338648?journalCode=rdat20

Contacts

For more information about the GCRF START SciArt project, please contact : Dr Jeremy Woodward


[1] ‘Ubuntu’ or ‘umntu ngumntu ngabantu’ in the isiXhosa language means ‘I am because you are’. In the Oxford Dictionary and Oxford Learners’ dictionary respectively, Ubuntu is defined as a quality that includes the essential human virtues of compassion and humanity or the idea that people are not only individuals but live in a community and must share things and care for each other.’

The hunt for an HIV vaccine – unique insights from an inspiring Cohort of women in South Africa

“We have been privileged to have worked with community members who are so committed to the research that could one day realize our shared vision of a world without AIDS.” 

Professor Salim Abdool Karim, Director of CAPRISA, South Africa.

Since HIV was found to be the cause of acquired immune deficiency syndrome (AIDS) in 1983, scientists have been working endlessly towards the development of an effective vaccine to end the global HIV pandemic which has claimed more than 32 million lives[1] and impacted millions more. Unfortunately, the best vaccine candidate we have had to date was from the famous Thai RV144 trial which only resulted in 31.2% efficacy (Rerks-Ngarm et al., 2009[2]). However, hope remains and more than 30 years after the discovery of HIV, we have uncovered many vulnerabilities of the virus which could lead to the development of an effective HIV vaccine to solve one of the big global challenges of our age.

One of the keys to a successful vaccine is the use of broadly neutralizing antibodies (bNAbs). These special antibodies bind to the HIV envelope protein and prevent the virus from infecting host cells. What makes them even more special is that they can bind numerous mutated versions of the virus and therefore overcome the problem of the HIV variability. Understanding the diverse ways that antibodies use to target the HIV envelope is important to the development of an HIV vaccine which can produce such unique and unusual antibodies and effectively protect vaccinated individuals from HIV infection.

My name is Dr Thandeka Moyo and I am a GCRF START grant-funded Postdoctoral Research Fellow at South Africa’s National Institute for Communicable Diseases (NICD), affiliated to the University of the Witwatersrand (Wits). Over the past few years, my colleagues and I have gained new insights into bNAbs in chronic HIV infection, insights which contribute significantly to the worldwide hunt for an HIV vaccine. Most recently, with access to the UK’s national synchrotron – Diamond Light Source (Diamond) – facilitated by the GCRF START grant, we were able to solve the structure for one member of a family of antibodies which has revealed a uniquely long loop in the light chain of the antibody – a loop up to three times longer than other published anti-HIV antibodies![3]  Such insights are exciting, providing opportunities not only to expand my skills and knowledge as an early career scientist but also to inspire further hope that we will one day have all the necessary information to design an effective vaccine to end the global HIV pandemic.

South Africa has the biggest HIV epidemic in the world, with an estimated 7.5 million people infected nationally according to UNAIDS[4]. In this article, I will outline some of the insights achieved over several years of investigating broadly neutralizing antibodies through women participating in the CAPRISA Cohort – a research programme based in the KwaZulu-Natal province of South Africa. Without these women enabling us to study their donated samples, we would still have many unanswered questions.

“The experiences of the CAPRISA bnAb cohort studies epitomize the strength of the relationship between CAPRISA researchers and the local communities – a relationship of respect and equality.”

Professor Salim Abdool Karim, Director of CAPRISA, South Africa.
The rural town of Vulindlela in KwaZulu-Natal, South Africa, where the CAPRISA Vulindlela Clinical Research Clinic is based. Photo credit: Dean Demos

Investigating broadly neutralizing antibodies in chronic HIV infection

A subset of individuals who are infected with HIV develop broadly neutralizing antibodies (bNAbs) in chronic HIV infection. Unfortunately, these special antibodies are very unusual with characteristics not found in most other antibodies that we have in our bodies. For example, these antibodies are highly mutated and have longer “arms” that reach out and bind to the virus. Most antibodies do not have these characteristics, so researchers have spent years studying these unique bNAbs to get a better sense of how to produce them with an HIV vaccine.

In our laboratory at the NICD, we study antibodies in HIV-infected women from KwaZulu-Natal who participate in the CAPRISA Cohort.  Established in 2003, this Cohort has tracked women over several years from before HIV infection, through to when a subset of them were just infected (acute stage), and years after infection (chronic stage). Throughout the course of the study, the women received healthcare and HIV counselling through the Cohort and have continued to participate in it for years. Blood samples were taken at various time points and from these samples we have been able to track the evolution of the viruses in these women as well as the way their antibodies have adapted throughout infection – with some women developing these special bNAbs.

The CAPRISA Cohort has been invaluable in providing us with novel information on how bNAbs develop as the virus mutates, as well as how we can engineer a vaccine strategy more widely to make these antibodies. This has helped us understand the development of bNAbs and how we can use these antibodies for an effective HIV vaccine. Outlined below are examples from three women in the Cohort (referred to as CAP256, CAP248 and CAP314 respectively) who have developed special antibodies.

CAPRISA Cohort participants CAP256 and CAP248

CAPRISA Cohort participant CAP256 became infected with HIV during the study and then re-infected with another variant form of HIV 15 weeks after initial infection – a phenomenon referred to as superinfection. A related virus to the superinfecting virus changed the immune response in this woman and she developed bNAbs after this event.  Scientists in the USA isolated antibodies from the blood donated by CAP256[5] and discovered that the best antibody isolated bound to the apex (the top region) of the HIV envelope protein. This antibody is the most potent antibody isolated to date that binds to this target and the exact mode of binding for this antibody was not understand until recently. Led by our collaborators at the National Institute of Health in the USA, a study of the high-resolution structure of this antibody bound to the HIV envelope using cryo-electron microscopy revealed that it uses two distinct mechanisms to bind to this region (Gorman et al., 2020[6]). The use of these diverse strategies is likely the cause of its extremely high potency. The antibodies from CAP256 are currently in an HIV prevention clinical trial with results expected in the next few years.

Another CAPRISA Cohort participant, CAP248, also developed bNAbs. Researchers isolated an antibody from this participant which was unusual in the HIV envelope site that it targeted. Using negative stain electron microscopy (Scarff et al., 2018[7]), they showed that this antibody from CAP248 bound to a target proximal to the viral membrane and parts of the antibody interacted directly with viral membrane (Wibmer et al., 2017[8]). This mode of binding is unique and represents a novel way an antibody can bind to the HIV envelope protein. This novel binding mechanism may provide insight into the design of an HIV vaccine candidate that can produce this type of antibody response.

Solving a unique antibody structure with the help of the GCRF START grant – CAPRISA Cohort participant CAP314

The last participant to highlight in this article is CAP314. CAP314 developed bNAbs within two years of infection which is a relatively short time for HIV-infected individuals to develop these special antibodies. We isolated antibodies from three families of antibodies that developed in this individual. One family of antibodies mutated over time in response to the mutating HIV variants circulating in CAP314 at the same time. We were able to solve the structure for one member of this antibody family by X-ray crystallography on Diamond’s i03 beamline, in 2019, with Dr Dave Hall as our local contact in the UK for the beamline session and access provided by the GCRF START grant. Solving the structure of this antibody has revealed its uniqueness in that it has an extremely long light chain loop. The loops of antibodies are like arms which reach out and attach to their target on the HIV Envelope. Most anti-HIV antibodies have long loops on the heavy chain of the antibody, but this antibody has a uniquely long loop – up to three times longer than other published anti-HIV antibodies – in the light chain of the antibody. This long light chain loop reaches into the HIV envelope protein and makes the necessary contacts for this antibody to bind to the virus and stop it from infecting cells. Novel and unique binding mechanisms of antibodies like these give us important insights which could help us in our quest to design an HIV vaccine.

Aerial view of the UK’s national synchrotron, Diamond Light Source, located at the Harwell Campus in Oxfordshire, UK. ©Diamond Light Source

Global solidarity, shared responsibility through phenomenal CAPRISA Cohort and collaborations  

We are very grateful to the women in the CAPRISA Cohort who make our vital work towards the goal of HIV prevention possible, and to our collaboration with the GCRF-funded START grant. START is a phenomenal initiative supporting capacity development of structural biologists throughout Africa by providing improved access to world class synchrotron equipment, mentoring and expertise. I have been fortunate to have found extremely supportive mentors in START Co-Investigator’s (CoI’s), Prof. Penny Moore and Prof. Lynn Morris, who have encouraged my independence and supported me throughout my Postdoctoral studies.

“Over the last decade, we have learned an incredible amount about how some HIV infected women make broadly neutralizing antibodies. These insights have significantly contributed to HIV vaccine design. This has only been possible because of the extraordinary commitment shown by CAPRISA Cohort donors who come back again and again, and the clinical staff who care for them. We are truly indebted to them.” 

GCRF START Co-I, Prof. Penny Moore, University of the Witwatersrand and the National Institute for Communicable Diseases.

The UN states that a core principle of the 17 Sustainable Development Goals (SDGs), and of the AIDS response, is that “no one should be left behind. The AIDS epidemic cannot be ended without “the needs of people living with and affected by HIV, and the determinants of health and vulnerability, being addressed.”– UNAIDS[9]

Read more here about HIV/AIDS and the UN Sustainable Development Goals.

Read more about World AIDS Day 2020 here.

World AIDS Day 2020 – Global solidarity, shared responsibility. Photo credit: UNAIDS

More about Dr Thandeka Moyo

 GCRF START Postdoctoral Research Fellow, Dr Thandeka Moyo, holds a BSc with distinctions in Biochemistry and Microbiology and a BSc (Hons) in Biochemistry from Rhodes University. She went on to obtain a MSc (Med) and PhD in Clinical Science and Immunology from the University of Cape Town where she looked at the mechanisms used by various HIV strains to gain resistance to broadly neutralizing antibody responses. Based at South Africa’s National Institute for Communicable Diseases and affiliated to the University of the Witwatersrand, Thandeka’s postdoctoral research involves understanding the structure and function of HIV neutralizing antibodies by X-ray crystallography. More recently she has added SARS-CoV-2 to her research focus, developing serological assays to measure humoral responses to infection and vaccination. 

Dr Thandeka Moyo, GCRF START Postdoctoral Research Fellow at the National Institute for Communicable Diseases, affiliated to the University of the Witwatersrand, South Africa. ©Diamond Light Source

More about Prof. Penny Moore

GCRF START Co-I, Prof. Penny Moore, is a Reader and DST/NRF South African Research Chair of Virus-Host Dynamics at the University of the Witwatersrand and the National Institute for Communicable Diseases. She holds a joint appointment as Honorary Senior Scientist in Virus-Host Dynamics at the Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal.  Moore co-directs a team of more than 15 scientists and 10 graduate students, with the team’s research focused predominantly on HIV neutralizing antibodies and their interplay with the evolving virus.

Prof. Penny Moore, GCRF START Co-I, Reader and DST/NRF South African Research Chair of Virus-Host Dynamics at the University of the Witwatersrand and the National Institute for Communicable Diseases, South Africa.
©Diamond Light Source

Footnotes

[1] https://www.unaids.org/en/resources/fact-sheet accessed November 2020

[2] RERKS-NGARM, S., PITISUTTITHUM, P., NITAYAPHAN, S., KAEWKUNGWAL, J., CHIU, J., PARIS, R., PREMSRI, N., NAMWAT, C., DE SOUZA, M. & ADAMS, E. 2009. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. New England Journal of Medicine, 361, 2209-2220; doi: 10.1056/NEJMoa0908492.

[3] The structure was solved by Dr Thandeka Moyo from the NICD, South Africa, and Taylor Sicard and Dr Jean-Philippe Julien from the University of Toronto, Canada.

[4] http://aidsinfo.unaids.org/ accessed November 2020.

[5] The donor was identified by Prof. Penny Moore in research that commenced in 2005.

[6] GORMAN, J., CHUANG, G.-Y., LAI, Y.-T., SHEN, C.-H., BOYINGTON, J. C., DRUZ, A., GENG, H., LOUDER, M. K., MCKEE, K. & RAWI, R. 2020. Structure of Super-Potent Antibody CAP256-VRC26. 25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition. Cell Reports, 31, 107488, https://www.cell.com/cell-reports/pdf/S2211-1247(20)30366-1.pdf.

[7] SCARFF, C. A., FULLER, M. J., THOMPSON, R. F. & IADANZA, M. G. 2018. Variations on negative stain electron microscopy methods: tools for tackling challenging systems. JoVE (Journal of Visualized Experiments), e57199. https://www.jove.com/t/57199/variations-on-negative-stain-electron-microscopy-methods-tools-for.

[8] WIBMER, C. K., GORMAN, J., OZOROWSKI, G., BHIMAN, J. N., SHEWARD, D. J., ELLIOTT, D. H., ROUELLE, J., SMIRA, A., JOYCE, M. G., NDABAMBI, N., DRUZ, A., ASOKAN, M., BURTON, D. R., CONNORS, M., ABDOOL KARIM, S. S., MASCOLA, J. R., ROBINSON, J. E., WARD, A. B., WILLIAMSON, C., KWONG, P. D., MORRIS, L. & MOORE, P. L. 2017. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape. PLoS Pathog, 13, e1006074. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006074.

[9] https://www.unaids.org/en/AIDS_SDGs accessed November 2020.

Next steps with the GCRF START grant: building on 30 years of successful UK-Africa collaboration and capacity building in energy materials science

“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.  

Prof. Phuti Ngoepe, Director of the Materials Modelling Centre at the University of Limpopo in South Africa, and GCRF START Co-Investigator. ©Diamond Light Source 

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.[1]

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.”

Prof. Sir Richard Catlow, GCRF START Co-Investigator, Professor of Catalytic and Computational Chemistry at the University of Cardiff,
and Professor of Chemistry at University College London in the UK. Photo credit: The Royal Society. ©Diamond Light Source

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.”

Improving solar energy storage is one of many sustainable energy solutions to mitigate the adverse effects of global climate change.
Photo credit: Rebekka Stredwick. ©Diamond Light Source

“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.”

Aerial photograph of the UK’s national synchrotron, Diamond Light Source. ©Diamond Light Source

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”[2]. Click here for a full biography.

Publications: https://www.researchgate.net/profile/Phuti_Ngoepe

About Professor Sir Richard Catlow

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.[3]

Publications: https://scholar.google.co.uk/citations?user=eQRHK8EAAAAJ&hl=en

About Dr Happy Sithole

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.


[1] http://www.thepresidency.gov.za/national-orders/recipient/phuthi-ngoepe-1953-%E2%80%93

[2] Source: http://www.thepresidency.gov.za/national-orders/recipient/phuthi-ngoepe-1953-–

[3] Source: https://royalsociety.org/people/richard-catlow-11198/

Computational modelling and experimental science for sustainable energy storage, mineral processing and alloy development

“We have such a lot of potential insight and capacity in Africa which can contribute towards the whole wellbeing of the world and the good of humankind.”

Prof. Phuti Ngoepe, GCRF START Co-Investigator, Director Materials Modelling Centre, University of Limpopo, South Africa

Computational modelling and experimental science have always gone hand in hand. In the past, in my research, this was with laser spectroscopy to extract optimum information from both techniques. 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 capacity building even further, addressing global energy and climate challenges, building on more than 30 years of successful collaboration with UK scientists.

My name is Phuti Ngoepe, and I am Senior Professor and Director of the Materials Modelling Centre at the University of Limpopo (UL) in South Africa and a GCRF START Co-Investigator.  Our group uses computational modelling to study materials related to energy storage, mineral processing and alloy development themes. This research contributes to important energy and climate Sustainable Development Goals by investigating energy materials (including raw materials) for improvements in batteries central to the development of electric vehicles, solar energy storage and electricity utility backups.  Efficient mineral processing methods, which focus on water, energy and environmental conservation in the mining sector, are becoming imperative in Africa. Therefore, ‘greener’ water conserving and cost-effective approaches to mineral recovery and processing are also explored.

These themes are studied through collaborations with experimental teams using UL’s computational facilities and a petascale national computational facility at the South African national Centre for High Performance Computing (CHPC) in Cape Town, using a wide range of academic and commercial software for simulations.  Specific areas of study include computational approaches to produce nanostructures for cathodes of Li-ion batteries and emerging batteries, beneficiation of raw materials within all three themes of energy storage, and mineral processing and alloy development.

Phase stabilities of precious and light metal alloys have been examined from a combination of energetics, elastic properties and phonon dispersions, providing valuable information for aerospace applications, shape memory devices and generally powder metallurgy processing. The latter is undertaken in collaboration with South Africa’s Council for Scientific and Industrial Research (CSIR) and the University of South Africa (UNISA), the University of Cardiff (UK) and University College London (UK). Commercialisation processes are continuously pushing us out of our comfort zones, and we have even stretched ourselves to image and imitate processes that take place inside reactors in industrial pilot and production plants to help understand and solve challenging problems.

A decade ago, the mineral processing industry in South African mines approached South African universities, including UL and the Department of Science and Innovation (DSI) to employ blue sky research in modernising ways of mining and mineral extraction. In response, our group has developed stability protocols for metal sulphides hosting precious metals and proofs of concept, using computational modelling for the design of reagents that can efficiently extract metals from mineral ores, including those occurring in the Limpopo Province here in South Africa. Mineral processing is conducted with the University of Cape Town (UCT), the BGRIMM (Beijing General Research Institute of Mining and Metallurgy, China) and South Africa’s mineral mining research organisation, Mintek.

Prof. Phuti Ngoepe, Director of the Materials Modelling Centre at the University of Limpopo in South Africa and GCRF START Co-Investigator. ©Diamond Light Source

African perspectives on impact: energy storage solutions, capacity building and job creation

Ultimately, the potential impact of our collaborative research is huge.  For example, improved battery solutions for solar energy storage in Africa would mean better access to clean, affordable energy for working, cooking and learning at any time of the day or night. In addition, more efficient batteries in devices like mobile phones brings hope that one day phone batteries could be recharged just once a year!  The latter would make a huge difference to our rural people, the majority of whom rely on cell phones for communication but often struggle to access reliable energy sources to recharge.  With regards to industry and job creation, most of the materials involved in making the compounds we are investigating are mined in our region, such as manganese ores (South Africa has 80% of the world’s manganese ores), which means in terms of their beneficiation, we have possibility to harness the benefits locally by establishing industries related to energy storage.

Of course, impact is not just about scientific results; it is also about building the expertise of people. All our programmes have played and continue to play an important role in the training of postgraduate students and emerging researchers in South Africa and further afield. Much of this capacity building has benefitted from a fruitful collaboration of more than 30 years with Professor Sir Richard Catlow, Professor of Catalytic and Computational Chemistry at the University of Cardiff and Professor of Chemistry at University College London in the UK. Initially funded by The Royal Society, London (UK), and South Africa’s National Research Foundation (NRF), this partnership has afforded UK and African scientists opportunities to share skills, build capacity, and get involved in diverse and sustainable projects related to energy storage, mineral processing and alloy development. Today, our energy storage programme at the University of Limpopo is broad and involves several researchers and postgraduate students, with national and international collaborators from the South African Energy Storage Research Initiative (ESRDI), and from leading research organisations in the UK, USA and China.

We have produced highly competent systems administrators, many of whom are now based at other institutions and thus have been able to grow the capacity in computer modelling in our country. Students who qualified for PhDs in our programmes have continued and established computer modelling activities at other research institutions/universities, such as the University of South Africa (UNISA), Tshwane University of Technology, amongst others. National Laboratories such as the CSIR, Centre for High Performance Computing, Statistics South Africa, and commercial companies and SOE like Johnson and Matthey, Microsoft SA and Transnet are a few of the many high-profile labs we have been able to connect with in this way. The GCRF START grant will further assist us in our mission to develop expertise and people to take up leadership positions in South Africa and across the African continent, sharing their African perspectives on science with their counterparts in the UK.

Prof. Phuti Ngoepe, Director of the Materials Modelling Centre at the University of Limpopo in South Africa and GCRF START Co-Investigator. ©Diamond Light Source

A very promising START! Setting up of a new Li-ion battery cathode synthesis laboratory

“It is important that we invest for the long term and that the African scientific community engages with synchrotron science with the view to an African synchrotron being a reality in the not too distant future.” 

Professor Sir Richard Catlow, GCRF START Co-Investigator, The Royal Society, London; Cardiff Catalysis Institute (UK) and University College London (UK).

In terms of the science, the GCRF START grant enables us to use the latest synchrotron techniques on Diamond beamlines such as Extended X-ray Absorption Spectroscopy techniques (EXAS) and X-ray atomic pair distribution function (PDF), with our simulations complemented by experiments using samples produced from our new Li-ion Battery Cathode Synthesis Laboratory to help us understand how structural and electronic properties of the battery materials can be improved, especially in relation to the charging and discharging of batteries. 

The Li-ion Battery Cathode Synthesis Laboratory is being commissioned and co-ordinated by Dr Noko Ngoepe at the University of Limpopo. Dr Noko Ngoepe has the necessary experience through working with the cathode materials group which runs the manganese-based pilot plant in Nelspruit, and through his collaboration with the Argonne National Laboratory (USA) on the synthesis of the Nickel-Manganese-Cobalt (NMC) cathode materials. The products are lined up for further fluorination processing in South Africa, and for characterisation at Diamond together with our GCRF START Post-Doctoral researcher, Dr Cliffton Masedi.

This research also complements work carried out at the Cathode Materials Pilot Plant based in Nelspruit, South Africa, which was launched in Nelspruit in October 2017. It aims to see beneficiated manganese-based cathode materials for lithium-ion batteries developed locally at highly competitive costs, using South African raw materials. Our research is mainly intended to produce manganese rich cathode materials using the synthesis reactor. These materials will be characterised at UL and other collaborating institutions in South Africa that are participating in the Energy Storage Research Development Initiative, supported by the South African Department of Science and Innovation. It is further envisaged that some of the synthesised cathode materials will be doped in order to enhance their stability. 

Aerial view of Diamond Light Source Ltd, Harwell Campus, UK. ©Diamond Light Source

Nanostructures for cathodes of Li-ion batteries and emerging batteries

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. In terms of vehicle batteries, the three major considerations are the distance vehicles such as cars can travel before recharging their batteries; how quickly the batteries can be charged; and reasonable prices of batteries. Our research is contributing to global research efforts that will ultimately produce safe, cheap, ‘green’ batteries with a longer life cycle, increased storage capacity, a wider optimal temperature operating range, and higher power output.  Many of the technologies are there, it is now a question of how to improve them: how to increase the range of travel, the length of use, how to reduce cost, and how to reduce the carbon footprint.

The enhanced performance of batteries is now achieved with nano-architecture electrodes which is at the core of what we are doing. We use world leading computational approaches to produce such nanostructures for cathodes of Li-ion batteries and emerging batteries. Valuable insights are shed on disruptive structural changes that occur during charging and discharging, and how these can be brought under control. The electrodes we study consist of nanoparticles that aggregate to form bigger/secondary particles. The nano-architecture helps to increase the capacity of the batteries, the coherence and stability of which during operation, is vital.  Currently, computational modelling studies of manganese-based cathodes such as the spinel lithium manganese oxides and manganese rich NMCs of these are explored, predicting structural stabilities, 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 UK’s national synchrotron, Diamond Light Source (Diamond) with the START grant will be of enormous value.

Lithium-ion battery. Photo credit Rebekka Stredwick. ©Diamond Light Source

The impact for humanity and our planet is worth it!

“It takes more than a scientist to put things together. One must have one’s feet in different worlds: capacity building, relevance, the requirements of the science itself, and sustainable funding – it is a huge demand but worth it for humanity!”

Prof. Phuti Ngoepe, GCRF START Co-Investigator, Director Materials Modelling Centre, University of Limpopo, South Africa

With climate change and increasing socio-economic challenges facing both developing countries and the developed world, it has become more pressing than ever to invest in the next generation of scientists, and find novel, cost effective and clean energy storage solutions for the good of humanity and our planet. Most recently, during the global Covid-19 ‘lockdown’, we have watched how the world reduced its human activity (such as fossil fuel emissions) and for a short time in places nature bounced back! Yet creating sustained, lasting impact takes time and investment, as demonstrated by our research collaboration successes with the UK and others. In the space we find ourselves now (the ‘new normal’) how are we in Africa and the UK going to redefine our parameters for the benefit of future generations? What kind of world do we want to see post-Covid-19?  Collaborating well into the future with synchrotron science through the GCRF START grant is one positive answer to these difficult questions and the global challenges we all face.

It is an opportune time to strengthen this approach, as we are now in the era of Big Data, and the amount of data coming from various experimental facilities requires an integrated approach with modelling and simulation to exploit new approaches, such as Artificial Intelligence and Machine Learning. This GCRF START grant opens new avenues for exploring more hidden parameters and presents us with good opportunities.”

Dr Happy Sithole, Director of South Africa’s Centre for High Performance Computing (CHPC) and Centre Manager of the South African National Integrated Cyber infrastructure System (NICIS).

“It has been hugely rewarding working with Phuti and colleagues and with other African scientists over the last 30 years. 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.” – Prof. Catlow, GCRF START Co-Investigator, 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).

Professor Sir Richard Catlow, GCRF START Co-Investigator, Professor of Catalytic and Computational Chemistry at the University of Cardiff, and Professor of Chemistry at University College London in the UK. Photo credit: The Royal Society. ©Diamond Light Source
Click here to read more about the UN’s Sustainable Development Goals.

About Prof. Phuti Ngoepe

Prof. Phuti E Ngoepe is Senior Professor, Director of the Materials Modelling Centre at the University of Limpopo and holds the South African Research Chair on Computational Modelling of Materials. Awarded South Africa’s Order of Mapungubwe Silver, Prof. Ngoepe is a Founder Member of Academy of Science South Africa. Click here for a full biography. Prof. Ngoepe is a GCRF START Co-Investigator.

Prof. Phuti Ngoepe’s Publications

About Prof. Sir Richard Catlow

Prof. Sir Richard Catlow is Foreign Secretary and Vice President at The Royal Society, London, Professor of Catalytic and Computational Chemistry at Cardiff Catalysis Institute (UK), Professor of Chemistry at University College London (UK), and 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. “By combining powerful computational methods with experiments, Richard has made considerable contributions to areas as diverse as catalysis and mineralogy.[1]Prof. Catlow is a GCRF START Co-Investigator.

Prof. Sir Richard Catlow’s Publications


Footnotes

[1] Source: The Royal Society: https://royalsociety.org/people/richard-catlow-11198/

Taking energy materials to the next level

Investigating lithium-ion battery cathode materials for new generation improvements in sustainable energy solutions

“Ensuring access to affordable, reliable, sustainable and modern energy for all will open a new world of opportunities for billions of people through new economic opportunities and jobs, empowered women, children and youth, better education and health, more sustainable, equitable and inclusive communities, and greater protections from, and resilience to, climate change.”

UN Sustainable Development Goal 7 – Energy[1].

Lithium-ion batteries are used around the world in everyday portable electronics, in electric vehicles as well as in small power grids.  Scientists from the Energy Materials Research Group at the University of the Witwatersrand (Wits), South Africa, study the materials needed to improve the performance, safety, affordability and environmental footprint of lithium-ion batteries in line with important sustainable development goals (SDGs). A range of different cathode materials, as well as battery chemistry is studied to increase the understanding of the materials themselves: how various synthetic routes introduce impurity phases in these materials and how this can be avoided, and what the effects are of intentional doping and co-doping of these materials[2] to explore the impact they have on the structure, performance and impurities formed.

In this work, however, laboratory-based measurements do not often reveal a clear picture of the overall structure of the material, particularly when it contains lower concentrations of impurity phases which are either below the limit at which it can be detected or cannot be resolved from the major phase. It is therefore important to firstly, employ multiple techniques to provide complementary information and secondly, to obtain high-resolution measurements from synchrotron-based techniques which expose far more in terms of other phases in the samples. This is where the GCRF START grant plays a vital part.

“A synchrotron is millions of times more capable than the equipment in our labs in terms of brightness and detail, which makes access through the GCRF START grant to the UK’s national synchrotron, Diamond Light Source (Diamond), so significant.”

GCRF START Co-I, Prof. David Billing[3], Professor in the School of Chemistry and Co-PI of the Energy Materials Research Group at Wits.

Thus far we have data from various synchrotrons for high resolution X-ray diffraction and total scattering, as well as X-ray absorption spectrometry,” says Group Co-PI, Prof. Caren Billing, lecturer and Associate Professor in the School of Chemistry. “The GCRF START grant provides us with these important experimental opportunities, alongside vital skills training and knowledge exchange for building capacity and training emerging scientists in the energy materials field.”

The ultimate aim of the Group is to address global energy, climate, and health challenges which, amongst other aims, includes enabling better “access to clean and safe cooking fuels and technologies and expanding the use of renewable energy beyond the electricity sector, as well as to increase electrification in sub-Saharan Africa[4]. To this end, improved battery storage solutions are one of a creative mix of options the Group is examining, with the help of their collaborators, including the GCRF START grant.

“GCRF START asks us to consider questions in our research around the global challenges like: am I using components that are sustainable? Are we using elements which are abundant, affordable, and environmentally compatible?”, explains Prof. Dave Billing. “In doing so, we are mindful that the economic and social situations in Europe are different to Africa: different resources, different engineers, and different environments where the solutions have to work.  Everything costs energy, fundamentally, and the whole solution has to fit the community – these are the bigger picture questions that START encourages us to ask.”

Rural village in South Africa. Photo credit: Rebekka Stredwick. ©Diamond Light Source

Some of the Group’s early career scientists focus on various lithium metal ion phosphate materials, where they are studied with the idea of using earth abundant metal ions of benefit for cost effective production and materials with a possible impact on local mining opportunities[5] to support local economies. Two of these scientists – Michelle Thiebaut from South Africa and Michelle Nyoni from Zimbabwe – are PhD research students at Wits working on lithium iron phosphate and lithium vanadium phosphate respectively, examining them as cathode materials. Both students are supervised and mentored by Prof. Dave Billing and Prof. Caren Billing, and are part of a growing number of female scientists in the Energy Materials Research Group at Wits. Michelle Thiebaut and Michelle Nyoni describe the aims, techniques and motivation for their projects in the case studies below.

Michelle Thiebaut’s research: studying Lithium iron phosphate for battery cathode materials

“When Michelle Thiebaut first started in the group, she referred to herself as “an analogue girl in a digital world”. Michelle is now the forerunner in the group in processing XAS data and has been the only chemistry student to operate the Mössbauer spectroscopy instrument in the School of Physics at Wits.” – Prof. Caren Billing, Prof. Caren Billing, University of the Witwatersrand.

Being a new researcher in a field such as energy materials is both daunting and exciting because this field is always changing and improving. One needs to change and improve one’s skill set just as quickly but the key to continue is finding one’s motivation. My main motivation is seeing how people in South Africa and in other developing countries are struggling with everyday tasks, especially people in the rural areas – tasks like coming home and doing their homework. These tasks are things many people take for granted but I think it is unacceptable that people should be struggling to get by without proper, cheap and a long-lasting access to clean energy and electricity.

My second motivation is our planet. Every person has an obligation to the planet and to live an environmentally cleaner life. By pushing science in the energy materials field means also pushing towards a greener tomorrow. Trying to break through in this field as a young female is still a bit tough with people questioning your skill set and abilities but I do think we owe former female scientists a great deal of respect for paving the way for us.

My research field is energy materials, specifically investigating the cathode material LiFePO4 found in lithium-ion batteries. My focus with this material is to find a low cost, low energy synthetic route and to possibly improve the performance. LiFePO4 is a naturally occurring mineral but can also be synthesised in a lab. This naturally occurring mineral is not phase pure[6], meaning that the iron is commonly mixed with other metals such as manganese, magnesium and calcium which lowers the electrochemical performance[7]. Cathode materials are the positive electrodes of batteries and host the mobile ions (in this case lithium). The mobile ions are the ions that are removed from the structure when the battery is being charged and when the battery discharges (depletes) the ions are inserted back into the structure[8]. Current cathode materials are not only expensive to produce but also have some safety issues like overheating and short-circuiting associated with them – challenges we want to overcome.

Compared with other cathode materials, LiFePO4 has the advantage of being environmentally friendly, meaning there are no toxic materials presents, relatively cost efficient (no expensive metals/rare earth metals needed to synthesise the material) and is structurally and thermally stable. This means that the structure does not collapse with the removal of the mobile ions and the structure prevents the battery from overcharging as well as overheating, making this material safer to use[9]. However, one of the main disadvantages of LiFePO4 is the electrochemical performance such as the ionic (movement of ions through the crystal lattice)[10] and electronic (the ability to conduct or resist electric current), which are both important properties for cathode material. The mobile ions are restricted to movement through a 1-dimensional channel. Overcoming these problems has been the main focus for most research groups[11].

In my research, the electrochemical performance can be improved by doping with a selection of different metal ions. Inserting small amounts of metal ions into the structure can improve the battery performance differently depending on the metal. For example, nickel improves the stability of the structure and enhances the movement of lithium through the structure; copper improves the conductivity and improves the reversibility of the lithium ions in the structure; and manganese improves the reversibility as well as the stability of the structure.

Exploring materials through multiple techniques and collaborative efforts

To fully understand my material, it is very important to understand how the structure changes with small changes in my synthetic method and it is the collaborative effort between the Chemistry and Physics Departments at my university – the University of the Witwatersrand – which makes this possible, and through access to world class synchrotron sources to utilise the benefits of synchrotron data to further characterise my materials.  Selected samples were sent to the Synchrotron source at Brookhaven National Laboratory (NSLS-II) in the USA and to Diamond Light Source, the UK’s national synchrotron (Diamond), with access to Diamond provided by the GCRF START grant. We have obtained data from synchrotron X-ray diffraction and total scattering, as well as X-ray absorption spectroscopy. Having remote access to state-of-the-art synchrotron equipment in this COVID-19 travel restricted world is heaven-sent as the research can continue even when no travelling is allowed.

Aerial view of the UK’s national synchrotron, Diamond Light Source, located at the Harwell Campus in Oxfordshire, UK. ©Diamond Light Source

To thoroughly characterise my synthesised materials, I have made use of our lab-based diffractometers in the Chemistry department at Wits as well as the Mössbauer spectrometer and the Raman spectrometer in the Physics department.  Mössbauer spectroscopy and Raman spectroscopy are very useful for identifying crystalline (presence of long-range order of the atoms – regular arrangement of atoms over a longer distance) as well as amorphous (only the presence of short-range order of atoms – regular arrangement of atoms but only over a short distance) species in my samples. It is important to identify all the crystalline and amorphous species in the sample as impurities can occur in both forms and could negatively affect the battery performance.

Mössbauer spectroscopy is also useful for identifying the different local iron (Fe) environments present in my sample and to determine the form of iron – (oxidation state – Fe2+ is the desired state in my samples). Raman spectroscopy aids as a structural fingerprint that can be used to determine the identity of one’s material and is also useful in identifying any impurities present that the lab diffractometers could not detect due poor detection limits or due to the phase being amorphous. Synthesised samples can have a mixture of the desired product as well as impurities. There could be multiple sources for the formation of impurities but the most common causes can be either synthesis related (impurities that are formed due to a specific synthetic route) or impurities formed due to sensitivity to air (being exposed to air could cause some small changes like a change in oxidation state of a metal). Impurities can block the channel and subsequently the movement of the mobile ion and negatively affect the performance of the material and the battery.

Michelle Thiebaut, PhD student at the University of the Witwatersrand, South Africa. ©Diamond Light Source

Michelle Nyoni’s research: investigating Lithium vanadium phosphate for improved battery cathode materials

“Michelle Nyoni is a lady who, against many odds, is striving to obtain her PhD in energy materials. Impacted currently by Covid19 travel restrictions, Michelle is normally an ‘out-of-seat’ student who works full time at Chinhoyi University of Technology (CUT) in Zimbabwe and comes to South Africa for laboratory experiments at the University of the Witwatersrand during her teaching breaks as facilities for her research topic at CUT are limited. She has worked hard during her visits here to gather sufficient data so that she can process it when she returns home and brings with her a great deal of positivity and energy on each visit.” – Prof. Caren Billing, Prof. Caren Billing, University of the Witwatersrand.

While working in the farming sector in my home country of Zimbabwe, I realised that we are blessed with abundant renewable sources of energy – wind and solar – yet hindered by the challenge of how to store this energy effectively.  This is where the subject of batteries came into my life and where my current PhD research area fits in. I am investigating lithium vanadium phosphates as cathode materials for lithium-ion batteries. I began my PhD studies part-time, in 2017, at the University of the Witwatersrand in South Africa under the supervision of Prof. Caren Billing and Prof. Dave Billing, while working as a Chemistry Lecturer at CUT in Zimbabwe.

The inspiration for my research is the fact that South Africa is one of the biggest vanadium producers in the world and Zimbabwe is one of the biggest lithium producers in the world. Therefore, if the raw materials are locally available it will hopefully mean reduced cost of battery production. My research is directly linked to Sustainable Development Goal (SDG) 7 concerning affordable and clean energy but by contributing to SDG 7, my research also contributes to achieving SDGs 1-6 and 8-9.

The aim of my research is to do much of the material characterisation by focussing on understanding what is happening at the atomic level, asking questions like: what is happening with the structure and the material? Lithium vanadium phosphate materials have been made but is this synthesis method reproducible? Does it work for upscaling to commercial levels? How do slight changes within the synthesis (preparation method) affect the material? How does adding a dopant manipulate the electrochemical properties of my material?

Lithium vanadium phosphates are potentially effective because their various properties are attractive – they have a high thermodynamic and kinetic stability, and studies have shown they possess the potential to have very good electrochemical properties, which means they will have high specific energy, high working voltage, and good cycle stability. Normally, as batteries get older, the cycling gets poorer and poorer but lithium vanadium phosphate materials have good cycle stability and a lower price tag so they are not as expensive as some of the alternative materials that can be used.   There are also other advantages. Lithium vanadium phosphate materials provide improved safety, phosphates are more environmentally friendly than some other materials[12], and the vanadium contributes to the energy density as well as the voltage of the cells – in fact, our Lithium vanadium phosphate materials can reach voltages of over 4 volts! A key application is in electric vehicles which will benefit from increased length of travel due to the cycle stability of Lithium vanadium phosphate materials and the higher specific energy density, amongst other improvements due to the advantages described above.

The cathode material determines the voltage and capacity of a battery and the cathode in a lithium-ion battery is the positive electrode, which is normally a metal oxide that is responsible for being the source of lithium ions that carry the electric current when a battery is in use (discharging)[13]. There are various components that contribute to the cost of the battery with the cathode material within the battery usually one of the biggest costs, along with the separator[14]. The lithium vanadium phosphate materials that I am working with are cathode materials, therefore if we can source these locally within the SADC region of Africa, which includes 15 member states, this would make them a lot more affordable and accessible – which is the goal I am driving at.

Cutting edge techniques to determine material characterisation and impact

The techniques I will use in my PhD studies aim to test the lithium vanadium phosphate materials in depth so that I can contribute to research that is already available to help find viable products that can be used in Africa. Techniques include powder X-ray diffraction for the phase identification and Raman spectroscopy to enable me to determine the structural finger-print to ensure I am making the same product each time so that when I do change a parameter, the resulting effect will be clear. The GCRF START grant enables us to use the Diamond synchrotron for variable temperature experiments. Therefore, I would want to look out for how the material changes when we vary the temperature. I would also use XAFS– X-ray absorption fine structure spectroscopy at the B18 beamline at Diamond to study the changes in the neighbourhoods of particular atoms.

Another technique is transition electron microscopy – the determination of particle size and the distribution of those particles as well as the general morphology of the fine particles within the material. Additionally, I want to use STA – Simultaneous Thermal Analysis – to look at the thermal stability to ask a series of questions: how stable is my material and what happens under temperature changes? Does it break down or decompose? How does this effect the overall electrochemical properties because when we use these batteries they will heat up? What is the impact, for example, if I were to leave my phone device with a battery using these materials in the sun – how would the warmth of the sun affect it? Would the structure and performance be impacted? Therefore, I would do extensive electrochemical testing which includes cyclic voltammetry and electrochemical impedance tests, amongst others, to ensure the batteries with these materials are viable in the varied environmental conditions found across Africa, including very warm environments.

Michelle Nyoni, part time PhD student at the University of the Witwatersrand, South Africa, and Chemistry lecturer at
the Chinhoyi University of Technology (CUT), Zimbabwe. ©Diamond Light Source

The GCRF START grant: a bridge to sustainable growth and life-changing possibility

“Being part of the GCRF START collaboration has certainly taken our work in energy materials in South Africa to the next level!”

Prof. Caren Billing, University of the Witwatersrand

Many of the Group’s research projects are now at the point where data has been measured and obtained and the next learning curve of how to process the data is underway. Progress has been made, Prof. Caren Billing reports, which, without funding from the GCRF START Grant, would have been an even larger hurdle to overcome.The resultis cutting-edge science and capacity building, knowledge exchange and access to the latest techniques and technology, and a new generation of gifted scientists working towards the shared vision of developing novel, green and affordable energy solutions to inspire life-changing possibility in Africa and beyond.

“This is where the GCRF START grant comes in,” says Prof. David Billing, “it provides that bridge. Yes, there’s a skills gap here in Africa but for me that gap is possibly smaller than others; as long as we are staying current on the XRD side we can transition easily and tackle the more challenging newer techniques – there’s a whole suite of them but that will grow – and START gets us there! This is also what you need to get to the higher impact journals; it also to gets us closer to current answers and future possibilities rather than just ‘the best we can do’ with 30-year-old technology.”

“In terms of energy solutions, take the scenario of load shedding (electricity cuts) which poses a huge challenge across countries in Africa. The thought of being able to go off grid is vital. If you think about a rural village which is cooking using wood or charcoal and lighting in the form of paraffin or candles – this is energy poverty. If you can find a cheap, clean, sustainable source of energy to replace these – that would be life changing!”

GCRF START Co-I, Prof. David Billing, Professor in the School of Chemistry and Co-PI of the Energy Materials Research Group at Wits.
Prof. Caren Billing, Lecturer and Associate Professor in the School of Chemistry and Co-PI in the
Energy Materials Research Group at the University of the Witwatersrand, South Africa. ©Diamond Light Source
Prof. Dave Billing, Professor in the School of Chemistry and Assistant Dean in the Faculty of Science at the University of the Witwatersrand,
South Africa; and Co-PI of the Energy Materials Research Group and GCRF START Co-I. ©Diamond Light Source

Footnotes

[1] United Nations Sustainable Development Goals: Energy for Sustainable Development, https://sdgs.un.org/topics/energy

[2] Introducing small amounts of other metal ions into the structure during synthesis without changing the structure of the material

[3] Prof. David Billing is also Assistant Dean in the Faculty of Science at the University of the Witwatersrand, South Africa.

[4] https://www.un.org/sustainabledevelopment/energy/

[5] https://www.gcis.gov.za/sites/default/files/docs/resourcecentre/yearbook/yb1919-16-Mineral-Resources.pdf

[6] An easy way to picture this is in terms of ores. Generally, an ore will contain a mixture of minerals and hence is not ‘phase pure’.

[7] Information on the natural occurring triphylite (mineral data):  https://www.mindat.org/min-4020.html as well as an electrochemical comparison: https://www.sciencedirect.com/science/article/pii/S0378775301007273?casa_token=zcBRvEsb5SMAAAAA:Lrk2oIjOY-9W73OBWasFIrxQaP7mhWNfQ4HrYjzx7Ib_r95Pq4ix8eORm0IBm29G-izoI18

[8] How Lithium batteries work in: https://www.explainthatstuff.com/how-lithium-ion-batteries-work.html

[9] Advantages and disadvantages of Lithium-iron-phosphate v lithium ion: https://blog.epectec.com/lithium-iron-phosphate-vs-lithium-ion-differences-and-advantages

[10] See Figure 1. How the lithium ions move in a battery in: https://www.spectroscopyonline.com/view/techniques-raman-analysis-lithium-ion-batteries; see also: The channels through which lithium has to move in LiFePO4  in the paper:  Yi, T., Li, X., Liu, H. et al. Recent developments in the doping and surface modification of LiFePO4 as cathode material for power lithium ion battery. Ionics 18, 529–539 (2012). https://doi.org/10.1007/s11581-012-0695-y

[11] Jingkun Li, Zi-Feng. Past and Present of LiFePO4: From Fundamental Research to Industrial Applications. Chem. Volume 5, Issue 1, 10 January 2019, Pages 3-6 (2019), Elsevier. https://doi.org/10.1016/j.chempr.2018.12.012;

V.S.L. Satyavani,A. Srinivas Kumar,P.S.V. Subba Rao.Methods of synthesis and performance improvement of lithium iron phosphate for high rate Li-ion batteries: A review. Engineering Science and Technology 19, Issue 1, March 2016, Pages 178-188. Elsevier. https://doi.org/10.1016/j.jestch.2015.06.002;

Yi, T., Li, X., Liu, H. et al. Recent developments in the doping and surface modification of LiFePO4 as cathode material for power lithium ion battery. Ionics 18, 529–539 (2012). https://doi.org/10.1007/s11581-012-0695-y

[12] Hameed, S.A., Reddy, M.V., Sakar, N., Chowdari, B.V.R. & Vittal, J.J.; Royal Society of Chemistry Advances 2015, 5, 60630-60637

[13] See: ‘The four components of a Lithium battery’: https://www.samsungsdi.com/column/technology/detail/55272.html?pageIndex=1&idx=55272&brdCode=001&listType=list&searchKeyword=

[14] See: Figure 3. ‘Total material costs of all 10 considered cell chemistries plus Panasonic NCA Use Case differentiated in combined CAM cost, anode cost, and secondary material costs’ in: Wentker, M.; Greenwood, M.; Leker, J. A Bottom-Up Approach to Lithium-Ion Battery Cost Modeling with a Focus on Cathode Active Materials. Energies 201912, 504. https://doi.org/10.3390/en12030504

Addressing global challenges through a love of structural biology – my story as a GCRF START early career scientist

“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. 

Dr Carmien Tolmie, GCRF START Postgraduate Research Assistant at the University of the Free State, South Africa. Photo credit: Sean Dillow. ©Diamond Light Source 

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. 

Dr Carmien Tolmie using a Douglas Oryx Nano crystallisation robot to set up protein crystallisation trials at the University of the Free State’s Department of Microbial, Biochemical and Food Biotechnology. Photo credit: Rodolpho do Aido Machado. ©Diamond Light Source 

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.  

The UK’s national synchrotron, Diamond Light Source Ltd, on the Harwell Campus in Oxfordshire, UK. ©Diamond Light Source 

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.  

Dr Carmien Tolmie using a Rigaku X-ray diffractometer to determine diffraction data of a protein crystal at the University of the Free State’s Department of Microbial, Biochemical and Food Biotechnology. Photo credit: Rodolpho do Aido Machado. ©Diamond Light Source 

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  

Acknowledgements 

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.  

Dr Carmien Tolmie, GCRF START Postgraduate Research Assistant at the Department of Microbial,
Biochemical and Food Biotechnology, University of the Free State, South Africa. ©Diamond Light Source 

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 

Carmien’s profile on Research Gate Profile

Focus on fungal oxidoreductases for infectious disease drug targets

“The atomic structure of proteins provides an intimate insight into these magnificent macromolecules. This knowledge is crucial to truly understand how they function; whether it is to answer a burning question or to manipulate them – either to enhance if their reactions are desirable, or to inhibit if they are harmful.”   

Prof. Dirk Opperman, University of the Free State, South Africa 

Our research studies the structures of bacterial and fungal oxidoreductases (enzymes) which are possible drug targets to combat infectious disease. The current focus is fungal drug targets for fungal infectious diseases which can be very serious, especially for immune-compromised patients, such as those who are HIV/AIDS positive, organ transplant receivers, patients undergoing chemotherapy, and many more. This research is performed at the University of the Free State’s (UFS’s) Department of Microbial, Biochemical and Food Biotechnology1 and is led by the two Principal Investigators (PIs) of the Biocatalysis group at UFS, Prof. Dirk Opperman, who is a GCRF START Co-Investigator (Co-I), and Prof. Martie Smit. In our laboratory, we have solved the structures of a number of bacterial and fungal enzymes by X-ray crystallography over the past few years, two of the most recent – solving the structures of fungal cytochrome P450 reductase (Dec 2019) and Baeyer-Villiger monooxygenase (Feb 2020) – were assisted by the GCRF START grant and published in the journals Scientific reports2 and Catalysts3 respectively, as described later in this article.   

Dr Carmien Tolmie conducting molecular biology experiments at the University of the Free State’s Department of Microbial,
Biochemical and Food Biotechnology. Photo credit: Rodolpho do Aido Machado. ©Diamond Light Source 

The scale of the Fungal infection and drug resistance challenge  

Currently, there are three classes of anti-fungal drugs that are used to combat infectious fungal disease, but there is an increasing number of drug resistant (and even multi-drug resistant) fungi against these drugs meaning that these pathogenic fungi have become or are becoming resistant to the current medication used to treat patients. If no drugs are effective against invasive opportunistic fungi, the prognosis for immune-compromised patients is very poor, and many people will die. 

“It is therefore imperative that we search for and develop new antifungal compounds to address the growing challenge [of drug-resistance to opportunistic fungi], which impacts countries across Africa, as well as globally. This is especially urgent if the world is to meet the UN’s Sustainable Development Goals of Health and Wellbeing and Food Security by 2030.” 

Dr Carmien Tolmie, University of the Free State, South Africa 

Fungal infections are often underreported and because of this the extent of the situation is not fully known.  In South Africa, this is of particular concern because of our high incidence of HIV/AIDS. For example, one group4 reported that 90 % of HIV/AIDS positive patients on prolonged treatment contract oropharyngeal candidiasis (also called Thrush), an infection caused by a yeast, which is a type of fungus called Candida  (Dos Santos Abrantes, McArthur and Africa 2014). However, this is only one statistic, and the problem is much wider. In another example, Cryptococcal meningitis is a deadly brain infection caused by the soil-dwelling fungus Cryptococcus. Worldwide, nearly 220,000 new cases of cryptococcal meningitis occur each year, resulting in 181,000 deaths, most of which occur in sub-Saharan Africa (CDC, 2020). 

Using the powerful beams of Diamond’s synchrotron light to determine protein structures 

Our quest to find new drug targets involves examining the chemical processes that happen in the fungal cell in order to keep the cell alive. We choose an enzyme – a special type of protein involved in these processes – which will be a good target for anti-fungal medication. The experiments we do to produce our protein crystals include molecular biology, protein expression, purification and crystallisation.  We clone the gene that encodes the enzyme and insert it into a suitable host to produce the protein, such as the bacterium Escherichia coli, by protein expression methods. Escherichia coli is easy to manipulate and inexpensive to culture in large volumes. We then isolate the enzyme by protein purification methods which exploit the physicochemical properties of the enzyme to separate the target from the host proteins, and crystallise it before we examine it by X-ray crystallography.  

Dr Carmien Tolmie purifying proteins using an AKTA chromatography system at the University of the Free State’s Department of Microbial,
Biochemical and Food Biotechnology, South Africa. Photo credit: Rodolpho do Aido Machado. ©Diamond Light Source 

We use an in-house crystallisation robot at UFS to prepare the crystallisation trials and we regularly collect crystal diffraction data via remote access at the macromolecular beamlines of the UK’s national synchrotron –  Diamond Light Source (Diamond). This is a great help as we can control the beamline equipment from our offices, so we don’t incur the expense of travelling to the UK to use synchrotron techniques essential for our research. While we have X-ray diffractometers at the University of the Free State, they are not nearly as powerful as the beamlines of the Diamond synchrotron. Diamond’s beamline hardware has been developed to such an advanced stage that data collection can proceed very rapidly, enabling us to collect data much faster (minutes) than at our home sources (days). This high throughput is essential when searching for and identify tiny molecules that might potentially bind to the protein and possibly act as inhibitors, as large libraries of fragments must be screened. 

“The brilliant light generated by Diamond (10 billion times brighter than the sun!)  enables us to determine the structure of the proteins to extremely high resolutions, as well as structures from small or weakly diffracting crystals that we cannot study with our own laboratory techniques.” 

Dr Carmien Tolmie, University of the Free State, South Africa 

 We use the protein structure to search for small molecules that will bind to the enzyme and possibly stop it from working (act as inhibitors). In Biocatalysis, knowledge of the protein structure can identify ways in which one can change, or mutate, the enzyme to perform the specific reactions desired.  If the protein is a drug target, the structure can be used in Structure-Based Drug Discovery to develop new medications. This process can also be used for other applications like developing new pesticides for agriculture. Therefore, the next step in the research process is to use fragment screening methods  to identify lead compounds that can be further developed into inhibitors, thus helping develop a next generation drug. The fragment screening is done in collaboration with Prof. Frank von Delft and the XChem group on the I04-1 beamline at Diamond through the GCRF START grant and will be undertaken once Covid19 travel restrictions are lifted.  

Beamline I04-1 Experimental Hutch – Sample changer and sample environment at the UK’s national synchrotron, Diamond Light Source. ©Diamond Light Source Ltd 

Solving the structures of fungal cytochrome P450 reductase and Baeyer-Villiger monooxygenase  

Recently, we were able to solve and gain new insights into the structures and mechanisms of the fungal cytochrome P450 reductase (CPR) from Candida tropicalis and the Baeyer-Villiger monooxygenase BVMOAFL210 from Aspergillus flavus, research that was made possible by the GCRF START grant. The results were published in the journals Scientific reports and Catalysts respectively, and the research on the CPR was done in collaboration with scientists from the University of Cape Town5, who are also part of the START project. The publications were co-authored by START PDRAs Ana Ebrecht (first author on CPR paper) and Rodolpho do Aido Machado (co-author on BVMOAFL210).  

The CPR plays a pivotal role in primary and secondary metabolism of different species, from bacteria to animals and plants. In fungi, it supplies electrons to enzymes that are vital for the survival of the organism. The CPR mechanism is complex and involves conformational changes that need to be finely tuned to optimise the process. The structural characterisation of the CPR helps to understand how this process occurs and what are the differences with the human homolog, opening the possibility to use it as a drug target. The structure and mutation data of BVMOAFL210 allowed us to better understand the role of the amino acid at a specific position in the enzyme, in terms of regioselectivity (the position in the substrate where the oxygen atom is inserted) as well as the sulfoxidation (the number of oxygen atoms inserted in a sulfur-containing compound). This residue may be used in future studies for directed evolution experiments to evolve the enzyme to catalyse a desired reaction.  

In order to achieve the results, we first needed to produce pure protein. The proteins were crystallised by the vapour-diffusion method with the Douglas Oryx Nano crystallization robot located in our crystallography lab in our department. In these experiments, a library of 384 crystallisation conditions were screened and a few conditions yielded crystals. These crystals were cryo-cooled and shipped at liquid nitrogen conditions in a specialised container to Diamond where we collected data on the macromolecular crystallography beamlines through remote access. We processed the data and solved the structure with programs from the CCP4 suite of macromolecular data processing software. The proteins were characterised further by investigating their kinetic properties with several spectrophotometric assays using a UV/Visible light spectrophotometer.  

Dr Carmien Tolmie using a Douglas Oryx Nano crystallisation robot to set up protein crystallisation trials at the University of the Free State’s Department of Microbial,
Biochemical and Food Biotechnology, South Africa. Credit Rodolpho do Aido Machado. ©Diamond Light Source 

For BVMOAFL210, we created mutations at a specific position and determined how these mutations alter the biocatalytic profile of the enzyme using whole-cell biotransformation experiments, followed by Gas-Chromatography Mass Spectrometry (GC-MS) analyses. In terms of the fungal cytochrome P450 reductase (CPR), the next steps will be to use the CPR for fragment screening to gain further, more detailed insights. 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.  

Benefitting from increased research capacity through the GCRF START grant 

The grant has contributed greatly to the research capacity of the Biocatalysis and Structural Biology Research group, making it possible to appoint a START Postdoctoral Research Assistant (PDRA) who focused on structural biology research, the research itself partially funded by START. START also helped to develop the skills of the researchers in the group by funding workshops, as well as workshop attendance, and a research exchange of the START PDRA to the UK in 2019. In addition, START has introduced us to world-class scientists at Diamond and other institutions who we can consult if we need advice on our experiments.  

“With this sharing of knowledge, capacity building and cutting-edge research enabled by the GCRF START grant, it is our fervent aim to make a lasting, positive impact in terms of sustainable health, well-being and food security solutions now, and well into the future.”

Dr Carmien Tolmie, University of the Free State, South Africa 

Click here to read more about the UN’s Sustainable Development Goals  

Acknowledgements  

We would like to thank Prof. Trevor Sewell from the START Centre of Excellence at the University of Cape Town’s Aaron Klug Centre for Imaging and Analysis for the pivotal role he has played both in GCRF START and Structural Biology in South Africa. The START Centre of Excellence is a collaborative, shared resource where participants in the START programme can access everything they need to get started with their research, such as advice and the necessary equipment which may not be available in their own laboratories elsewhere. This also includes the technological support and expertise to access the UK’s national synchrotron – Diamond Light Source – through the GCRF START grant (such as support with sample preparation, shipping, and remote access experiments). 

Dr Carmien Tolmiehttps://orcid.org/0000-0001-9095-3048 

Dr Carmien Tolmie, researcher in the Department of Microbial, Biochemical and Food Biotechnology
at the University of the Free State, South Africa. ©Diamond Light Source 

Prof.Dirk Oppermanhttps://orcid.org/0000-0002-2737-8797 

Prof. Dirk Opperman, researcher in the Department of Microbial, Biochemical 
and Food Biotechnology at the University of the Free State, South Africa. ©Diamond Light Source 

Footnotes

[1] Research in the Department falls broadly into three main areas: (i) production of safe and novel food products, (ii) biocatalytic production of chemicals or bioremediation of chemical pollution, and (iii) improvement of human and animal health. Our Biocatalysis Group focuses heavily on biocatalysis which involves the use of one or more enzymes, either as cell-free enzymes or enzymes in whole cells, to convert a substrate into a value-added product. This includes converting alkanes, alcohols, fatty acids or monoterpenes into value added building blocks of pharmaceuticals, bio-plastics, cosmetics, flavours and/or fragrances.

[2] Ebrecht AC, Van der Bergh N, Harrison STL, Smit MS, Sewell BT and DJ Opperman (2019). Biochemical and structural insights into the cytochrome P450 reductase from Candida tropicalis. Scientific Reports 9:20088. doi: 10.1038/s41598-019-56516-6: https://www.nature.com/articles/s41598-019-56516-6

[3] 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: https://www.mdpi.com/2073-4344/10/3/339

[4] Dos Santos Abrantes PM, McArthur CP, Africa CWJ. Multi-drug resistant oral Candida species isolated from HIV-positive patients in South Africa and Cameroon. Diagn Microbiol Infect Dis 2014;79:222–7.

[5] https://www.news.uct.ac.za/article/-2020-03-12-sa-women-take-the-lead-in-structural-biology