Disentangling the neuromolecular networks involved in speech and language

As a biochemist/biophysicist working primarily with proteins, I am naturally drawn to the mechanisms of interactions of biological macromolecules. My name is Sylvia Fanucchi, and I am a senior Lecturer in the Protein Structure Function Research Unit (PSFRU) at the University of the Witwatersrand (Wits) in South Africa. I am interested in how things work at the molecular and atomic level, and how the structure of macromolecules leads to their function. This has inspired my research for the past six years which involves disentangling the neuromolecular networks involved in speech and language. With the GCRF START grant, the doors to collecting the detailed structural information we need through studying and obtaining crystal structures, have been opened for groups in Africa like ours. I have had multiple opportunities, thanks to the grant, to send crystals to the UK’s world class national synchrotron, Diamond Light Source (Diamond).

Senior Lecturer, Dr Sylvia Fanucchi, in the Protein Structure Function Research Unit at the University of the Witwatersrand in South Africa. Photo credit: Sylvia Fanucchi. ©Diamond Light Source

My research appeals so much to me because our ability to speak, to think, to read is fundamental to humankind. Indeed, my research question started with “what defines speech and language?” but has since expanded to include questions about cognition, reading, and a number of disorders associated with these such as Autism, Dyslexia, Epilepsy and Schizophrenia. Dyslexia, for example, occurs in at least one in 10 people world-wide, putting more than 700 million children and adults worldwide at risk of life-long illiteracy and social exclusion.[1].

Globally, it is estimated that one in 160 children has an Autism Spectrum Disorder (ASD), although estimates vary significantly across studies, and between developed[2] and developing countries[3]. In Southern Africa, very little is known about the prevalence ASD and it is understood that many cases go undiagnosed. Because these disorders can be debilitating and impact on the quality of life of those living with these disorders, and because there is currently no known cure, it is of utmost importance that the complex neuromolecular mechanisms that define these disorders be explored and far better understood. It is hoped that through our research more robust forms of therapeutics could be developed.

Piecing together neuromolecular complexes and networks

In my work, I investigate protein-protein and protein-nucleic acid interactions and try to piece together the neuromolecular complexes and networks that form in both space and time to better understand the mechanism of their interaction and how this is associated with language and cognition, as well as how changes in these may lead to certain disorders. I use an array of biochemical and biophysical techniques to achieve this study and the most prominent of these include, fluorescence anisotropy, isothermal titration calorimetry, hydrogen exchange mass spectrometry and single molecule kinetics. These techniques are used to study binding kinetics and thermodynamics as well as the dynamics and motions of molecules and their interactions with each other, such as the interaction between a protein and DNA, or the interaction between two proteins. The work we have done has mostly been conducted at the PSFRU but I also have collaborations with Dr Previn Naicker and Dr Stoyan Stoychev at the CSIR in Pretoria who assist with mass spectroscopy, and Dr Carlos Penedo[4] from the University of St Andrews in Scotland, UK, who assists with single molecule studies.

The promising biophysical studies conducted in this work will benefit greatly from detailed structural information, provided currently through access to Diamond with the GCRF START grant. Knowledge of the structures of macromolecular complexes allows us to fully understand our system at a level of detail that is otherwise unattainable. And this information, in addition to the dynamics/thermodynamics/kinetics data, will enable us to understand the complexity of these networks at atomic resolution. This will foster a deeper understanding of these mechanisms and enable detailed therapeutics to be designed that would help regulate these disorders, particularly if single strong contributing factors could be identified. Crystallography and solving the structures of the individual interacting partners, as well as of the complexes is therefore of fundamental importance in this project.

FOXP2 protein – the “the language gene”

The protein that sparked this investigation is a transcription factor (a protein that regulates the expression of genes) called FOXP2. FOXP2 was dubbed “the language gene” in the early 2000s when a mutation in this gene that severely impeded DNA binding was found to result in a form of verbal dyspraxia in a family of individuals in the UK. Because FOXP2 is a transcription factor, it is located in the nucleus of cells and its role is to bind to the promotor region of certain genes and facilitate/regulate their transcription to mRNA which ultimately results in the translation and thus expression of that particular protein. Therefore, the regulation of transcription (and hence translation) of any protein will have a direct effect on the functioning of that protein. Our focus is thus on transcriptional regulation because it is the process that initiates downstream effects and predicts which genes will be turned on or off and hence, crudely put, controls the way we function.

Over the past three years, this project therefore focused on the mechanism of DNA binding of FOXP2. Through this work we were able to meticulously describe what drives the interaction of the DNA-binding domain with cognate DNA. We identified electrostatic interactions that played a critical role, we studied binding sequences to gain insight into binding specificity and affinity, we outlined how a domain-swapped dimerisation event that is unique to this subfamily of FOX proteins was able to assist in the dynamics of the DNA binding event, and we described the thermodynamic and kinetic events that occur during binding. In essence, by describing how the transcription factor interacted with DNA, we were able to tell which sequences it preferred, which conditions were most favourable for transcription, and how the structure and fold of the protein was necessary for transcription to occur. Knowing this helps us understand what is necessary for certain genes to be turned on or turned off and how we could interfere with this process.

The focus of our work then moved from DNA binding to the complex network of neuromolecular protein-protein interactions and we began to piece together other interacting partners of FOXP2 and how these interactions affected transcriptional regulation. One specific interaction has yielded a very interesting link to Autism that we are currently exploring further. I have established a very fruitful collaboration with Dr Carlos Penedo from the University of St Andrews primarily through a Newton Fellowship from the Royal Society and the single molecule work done through this collaboration has helped to resolve intricate details about these interactions that I am very excited about[5].

Fast and remote access to diffraction and data collection with Diamond and the GCRF START grant

The opportunities to send crystals to Diamond with the assistance of the GCRF START grant have been revolutionary in enabling us to have fast and remote access to diffraction and data collection that would otherwise have been logistically far more difficult to achieve, and therefore far more sparsely accomplished. Unfortunately, up to now, crystallisation in this project has been a challenge and so far, we are yet to achieve the crystals we require. The fact that the proteins we are attempting to crystallise have not yet had their structures solved and published in the Global Protein Data Bank (PDB) attests to the challenge we knew we would face in obtaining good diffraction data. And while we have obtained some crystals successfully, none of the data we have obtained has been worthy of solving the structure. Nevertheless, the fact that we can obtain crystals is promising and I am determined to persevere with this work until we are successful.

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

My students are all working on aspects of this project. They work on protein-protein interactions, crystallisation and structural biology, biophysics, and biochemistry. I am currently supervising 5 PhD students and 4 MSc students from diverse backgrounds, 8 of whom are females. I also have 2 postdoctoral Fellows – one from Lesotho and one from Kenya – that have worked under me for the past two years.  In 2020, I graduated 2 PhD students and 2 MSc students. The students are given the autonomy to operate equipment, design experiments and analyse their data. Where possible, and covid-19 pandemic permitting, I encourage them to participate in international workshops and to visit other labs to gain experience and exposure.

Riyaadh Mayet is one of the early career MSc Students in my team.

“The GCRF START grant has enabled the African continent to foster development in synchrotron techniques through collaboration with the UK.” she says. “My MSc project deals with the structural biology of DNA-binding by the TBR1 T-box transcription factor implicated in Autism. The grant has enabled me to send my samples to the Diamond Light Source for diffraction, and without it, it would be very difficult if not impossible to obtain such data. It has also taught me how to better collaborate with fellow researchers, as well as given me the opportunity to learn how to diffract crystals to obtain atomic resolution data. Lastly, I have indirectly benefitted through learning about protein crystallography from fellow researchers who have used the START grant.”

Dr Sylvia Fanucchi with some members of her team of researchers at the Protein Structure Function Research Unit, at the University of the Witwatersrand in South Africa. From left: Ilan Kirkel, Joni Symon, Dr Ashleigh Blane, Heather Donald, Dr Sylvia Fanucchi, Dr Monare Thulo, Riyaadh Mayet and Aasiya Lakhi.
Photo credit: Sylvia Fanucchi. ©Diamond Light Source

Despite the challenges we have encountered with solving structures in this project, I am very grateful for the support received through the GCRF START grant and the support structures put in place – in particular, in bringing together a strong network of South African crystallographers. Knowing that I have this group of colleagues available across the country that forms a support structure is very reassuring. I am confident that the assistance and opportunities offered to me by this grant over the years is going to result in the ultimate success of my crystal structure dreams for this project and I am both grateful and excited for what the future holds.

Commenting on Sylvia’s research project and the access to infrastructure such as the Diamond synchrotron, Head of School of Molecular and Cell Biology (MCB), Prof Marianne J. Cronje, says,

“I am wholly in support of these research endeavours. Dr Sylvia Fanucchi is an incredibly talented researcher and her position within the school’s Protein Structure Function Research Unit strengthens her efforts by providing access to high-end research infrastructure to support her research in the school.”

Senior Lecturer, Dr Sylvia Fanucchi, in the laboratory at the Protein Structure Function Research Unit, University of the Witwatersrand in South Africa.
Photo credit: Sylvia Fanucchi. Diamond Light Source

Addressing disability is referenced in many of the UN’s Sustainable Development Goals (SDGs), namely health, education, economic growth and employment, inequality, accessibility of human settlements, and others.  Read more about the SDGs here.


[1] https://www.dyslexia-and-literacy.international/wp-content/uploads/2016/04/DI-Duke-Report-final-4-29-14.pdf accessed 20.02.2021

[2] In the USA~10% of school children struggle with dyslexia and ~1 of every 59 school children is diagnosed with ASD (Yuhang Lin et al Int. J. Environ. Res. Public Health 2020, 17, 7140). The number with ASD has increased over the years reflecting both an increase in awareness as well as a potential increase in environmental triggers although the disorder is currently believed to be predominantly genetically determined.

[3] https://www.who.int/news-room/fact-sheets/detail/Autism-spectrum-disorders (accessed 20.02.2021)

[4] https://risweb.st-andrews.ac.uk/portal/en/persons/carlos-penedo(e1903c4a-e36d-4555-9c7e-e604c9873ba0).html

[5] Thulo M, Rabie MA, Pahad N, Donald HL, Blane AA, Perumal CM, Penedo JC, Fanucchi S. Biosci Rep. 2021 Jan 29;41(1):BSR20202128. doi: 10.1042/BSR20202128

Promising first steps towards an inhibitor targeting the South African HIV-1 subtype C protease (C-SA PR)

In a bid to design clinical drugs to improve health outcomes for people living with a particular strain of HIV and its mutants, scientists at the University of the Witwatersrand’s Protein Structure-Function Research Unit (PSFRU) in South Africa have embarked on a clinical drug discovery journey with promising results. The aim of the research, which receives funding from the GCRF START grant, is to develop a novel inhibitor specifically designed to target the South African HIV-1 subtype C protease (C-SA PR) and its mutants.

The purpose of developing an inhibitor is to stop C-SA PR’s activity by preventing the formation of mature copies of the human immunodeficiency virus (HIV). This would improve health outcomes in line with Sustainable Development goals across South Africa by increasing drug efficacy, reducing adverse side effects and drug resistance, as well as benefitting populations infected with the HIV subtype C in other sub-Saharan countries, India, China and Brazil[1].

GCRF START Post-Doctoral Research Fellow, Dr Ramesh Pandian (L), discussing crystallisation set up with GCRF START Co-I, Prof. Yasien Sayed (R), for the screening of crystals at the Protein Structure-Function Research Unit, University of the Witwatersrand, South Africa. Photo credit: Ramesh Pandian. ©Diamond Light Source

There is no permanent cure for HIV/AIDS which has claimed the lives of an estimated 32.7 million people globally since the beginning of the HIV pandemic (UNAIDS, 2020[2]). A number of drugs have been developed and approved by the USA’s Food and Drug Association (FDA) to increase the quality and duration of life in HIV infected individuals in some parts of the world. However, these are not specific to the HIV-1 protease subtype C which is dominant in South Africa – a country with approximately 20% of the global HIV infection rate and 10.44% of the global AIDS-related deaths (UNAIDS, 2020)[3].

To date, the scientists at the PSFRU have screened ten drugs in the FDA approved and Zinc drug databases, with seven hits that show promise for optimisation as inhibitors. They have solved one protein structure through sophisticated computational modelling, and with high-resolution X-ray crystallography data collected on beamline i03 at the UK’s national synchrotron – Diamond Light Source (Diamond) – have solved the structure of the South African HIV-1 subtype C protease (C-SA PR), the results of which were deposited in the global Protein Data Bank (6I45.pdb) in 2018 (Fig.1).

Fig.1 Ribbon structural representations of the HIV-1 subtype C-SA PR (cyan) and a mutant protease (purple). The structure of the mutant protease was determined using diffraction data obtained at the UK’s national synchrotron, Diamond Light Source (Diamond). PDB ID: 6I45. Sherry, D., Pandian, R., Achilonu, I.A., Dirr, H.W., Sayed, Y.  (2018), Crystal structure of I13V/I62V/V77I South African HIV-1 subtype C protease containing a D25A mutation. DOI: 10.2210/pdb6I45/pdb[4]; PyMOL Molecular Graphics System (Schrödinger LLC., Portland, USA[5]).

The research involves characterising the structure and function of the South African HIV-1 subtype C protease (C-SA PR) and its mutants using state-of-the-art computational and experimental methods made possible by the GCRF START grant. The scientists want to understand what role amino acid insertions and mutations the HIV-1 protease may have on clinical drug binding so they can design an effective inhibitor.

This research builds on a previous study[6], in which a blood sample was taken from a drug naive infant born to an HIV positive mother. To prevent the transmission of the virus to her baby, the mother had received reverse transcript inhibitor treatment (but not protease inhibitors) prior to the birth. However, when the baby was born it was found to be HIV positive and a mutation was present rendering current drug therapy ineffective.

“It is the results like this of other research on the South African HIV-1 C-SA PR, and the impact of the disease on individual lives and livelihoods, which drives our motivation. The fact that the baby had developed drug resistance mutations is very rare in mother-to-child transmission but no less concerning,” says Professor Yasien Sayed, who heads up the PSFRU and leads the research on the HIV-1 C-SA PR, “and there is evidence that some adults are also failing drug therapies. We therefore need to develop treatments which work more effectively against the HIV-1 C-SA PR and its mutants if we are going to improve clinical outcomes for the large population of HIV positive adults and children in South Africa, and further afield.”

Some of the first steps in the team’s drug discovery journey have been computational involving Molecular Dynamics Simulation[7] of the HIV wild type C-SA PR and its mutants. After this, drugs in various databases were screened[8].  As a result, the scientists found a promising drug from the FDA database that binds with the HIV wild type C-SA PR and its mutant with best docking scores and energies.

“We modelled the homology structures of the HIV wild type protease and its mutants using the template South African wild type HIV-1 Subtype C Protease (PDB ID: 3U71),” explains Dr Pandian who is a Post-Doctoral Research Fellow funded by the GCRF START grant specialising in the computational aspects of the research. “The structure was solved at 2.72Å using the software packages: Swiss model/modeler/I-Tasser, followed by experimental validation of the modelled structures with in-house computer software. We are excited by the preliminary results, which are better than the current FDA approved drugs, although the computational results now have to be proved through wet lab experiments, along with the best results from the screened from the Zinc database.”

Dr Ramesh Pandian, GCRF START Post-Doctoral Research Fellow at the University of the Witwatersrand, South Africa, in the process of solving of a crystal protein structure. Photo credit: Ramesh Pandian. ©Diamond Light Source

To conduct these studies, the PSFRU has its own computational and wet lab facilities for Molecular Dynamics simulation, docking studies, protein expression and purification. Screening of crystals is carried out using an Oryx8Protein Crystallization Robot (Douglas Instruments, UK) and testing of crystals using a home-source X-ray diffractometer. However, synchrotron facilities are not available on the African continent, so access to the Diamond Light Source synchrotron (Beamlines i03, i04, and also i04-1 and i24) is achieved remotely from the PSFRU lab in South Africa in order to characterise the structure and function of proteins at high resolution.

“Having access through the GCRF START grant to experimental synchrotron techniques like X-Ray crystallography at Diamond to obtain crystals and to solve the structures at high resolutions has been revolutionary for us,” reports Dr Pandian. “It is ultimately the combination of computational and experimental techniques that makes it possible to see how well the drugs are binding to optimise them for the South African HIV-1 subtype C protease (C-SA PR)[9].

“During the wet lab experiments,” Dr Pandian continues, “we can’t screen the whole drug library for the target protein and it’s very costly to purchase the drugs for screening. The theoretical part of the drug discovery method is therefore useful for generating three dimensional structures for any proteins when the crystal structures are not available in the PDB databases, and for sorting out the best ligand / inhibitors for the protein target before starting protein characterisation wet lab experiments.”

Aerial view of the UK’s national synchrotron, Diamond Light Source (Diamond) on the Harwell Campus, in Oxfordshire, UK. ©Diamond Light Source

Scientific results are not the only progress being made by the PSFRU team in their research which is meeting the UN’s Sustainable Development Goals for health (SDG 3); great strides have also been made in the PSFRU in terms of education and capacity building in structural biology (SDG 4) with more than 30 postgraduate students involved in the collaboration with the GCRF START grant since 2019. This includes Dr Ramesh Pandian, and Ms Mpho Setshedi who is a MSc. candidate working on the wet lab studies of the HIV-1 C-SA PR and its mutants.

“The research is meaningful,” says Ms Setshedi, “I feel like we are doing a good job and doing something to solve a challenge that impacts South Africa. I hope it contributes something big – an effective HIV inhibitor. In terms of what I am learning, there are challenges in this field but once you get the hang of the techniques you just need to persevere. Getting funding is a struggle in my field generally and there aren’t a lot of women doing this work. There have also been challenges caused by the COVID-19 lockdown in 2020 – but I haven’t let anything discourage me.”

Ms Mpho Setshedi, MSc. student at the Protein Structure-Function Research Unit, University of the Witwatersrand, South Africa. Photo credit: Mpho Setshedi. ©Diamond Light Source

Read more about the UN’s Sustainable Development Goals here


[1]: https://www.unaids.org/en/AIDS_SDGs accessed 3.3.2021

[2]https://www.unaids.org/en/resources/documents/2020/UNAIDS_FactSheet accessed 3.3.2021

[3] https://www.avert.org/professionals/hiv-around-world/sub-saharan-africa/south-africa accessed on 4 March 2021; For latest (2019) South African country statistics see: https://www.unaids.org/en/regionscountries/countries/southafrica

[4] https://www.rcsb.org/

[5] http://www.schroding-er.com ; Schrödinger, L. & DeLano, W., 2020. PyMOL, Available at: http://www.pymol.org/pymol

[6] https://pubmed.ncbi.nlm.nih.gov/30793914/ accessed 9.3.2021

[7]The Molecular Dynamics (MD) simulations of validated structures were performed under physiological conditions for 100ns using GROMACS software packages.  The MD simulated structures were analysed thoroughly and extracted the energy minimised structure for further analysis. Important parameters such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radiation of gyration (Rg) and hydrogen bonding analysis were carried out.

[8]The energy minimised structures of HIV wild type and its mutants were used for the screening of drugs from different data bases such as the Zinc database and FDA approved drugs database.

[9]The results of the binding pocket analysis of the protease complex form obtained by the docking studies with best ligand directed the scientists to modify the side chain with the combination of different R group of the drug to improve the binding affinity.

Engineering sustainable solutions – Enzymes to tackle toxic waste

The effects of human activity on climate change are evident in accelerated changes to global climatic conditions. As a result, there have been efforts to decrease human impact on the environment. This includes sustainable and environmentally friendly waste management systems, bioremediation of damaged ecosystems and biocatalysis as a replacement for conventional chemical synthesis in industries in line with the UN’s Sustainable Development Goals.

One way to address these challenges is through the use of enzyme biotechnology in which proteins (enzymes) are used as industrial catalysts. Nitrilases are widely used enzymes with potential in the production of high-value fine chemicals including medicines, bioremediation and waste management. A problem with using enzymes in environmental remediation is that naturally occurring enzymes are susceptible to degradation and inactivation under harsh conditions. They can, however, be engineered to make them more tolerant of these conditions. Nitrilases have intrinsically robust, spiral structures that suggest that substantial improvements in stability are possible.

My name is Lenye Dlamini and my PhD study in the Structural Biology Research group at the University of Cape Town (UCT) concerns the engineering of a cyanide-degrading nitrilase enzyme that can be used to remediate cyanide waste in the textile, electroplating and gold-mining industries. In particular, cyanide is used in huge quantities in these industries and spills or unsafe disposal results in environmental degradation and causes harm (and occasionally death) to humans and livestock.

Lenye Dlamini, PhD student at the University of Cape Town, South Africa. Photo credit: Lenye Dlamini. ©Diamond Light Source

My study will use predictive biophysical methods based on structural knowledge of cyanide degrading nitrilases to measurably improve their tolerance of non-optimal temperature ranges and enhance the operational stability of the enzyme so that they can be routinely used for safe and cheap disposal of cyanide waste.  The project builds on the work of Dr Andani Mulelu[1],2 and several of Prof Michael Benedik’s students at Texas A&M University who used directed evolution, a technique in which random amino acid mutations are introduced throughout the protein, to increase protein stability and ultimately led to the first structure of an enzyme of this type. My goal is to use this structure to identify specific amino acid changes that will lead to increased stability.

I am working from Prof Trevor Sewell’s (GCRF START Co-I) laboratory at UCT and the Electron Microscope Unit at the Aaron Klug Centre for Imaging and Analysis. My work is a component of the work on nitrilases being done by a large team of local and international collaborators (my first experience of collaborating with scientists outside of South Africa) that includes in South Africa: Dr Jeremy Woodward (GCRF START Co-I), Dr Gerhard Venter and Prof Roger Hunter at UCT, Prof Dean Brady at the University of the Witwatersrand, Dr Nishal Pharbhoo at UNISA; in Germany: Prof Andreas Stolz and Mr Erik Eppinger at the University of Stuttgart, Prof Markus Piotrowski of the Ruhr University at Bochum, and Prof Achilleas Frangakis at Goethe-University, Frankfurt.

While the direct impact of my research project is environmental, it has broader implications in a variety of industries. There is growing demand for biological agents and processes that will replace conventional processes of managing waste and chemical synthesis. Enzymes, including the nitrilases, have taken centre-stage in this regard and present not just an environmentally benign alternative but one that produces better reaction products (they are highly specific in the enantiomers and regions on compounds that they bind to, leading to more specific reaction products).

It is critical that we understand and can adapt enzymes for these new uses.  Nitrile-containing compounds are widespread in nature and are also utilised in industries including agriculture, mining, pharmaceuticals and the plastics and paper industry. Most nitrile-containing compounds are toxic, mutagenic, and carcinogenic. We are trying to design a way that will result in the use of harmful compounds as substrates for the catalysis of useful compounds in a sustainable and environmentally benign manner.

In my research on nitrilases, I am building on previous research skills I gained through my MSc. project which also benefitted from access to the UK’s national synchrotron, Diamond Light Source (Diamond). Through supporting research, workshops, mentoring and supervision, and other aspects of these labs, the GCRF START grant has also, by extension, supported the development of my research career. In addition, workshops presented by structural biologists from Diamond in South Africa, have enabled me to acquire skills that include molecular biology techniques, protein crystallography, electron microscopy and data collection at synchrotrons.

My Master’s research was in rational drug design against Mycobacterium tuberculosis using molecular and structural biology techniques. One of the main outcomes of my study was the crystal structure of thiamine monophosphate kinase from Mycobacterium tuberculosis, solved at a resolution of 2.19 Å, with data collected using the i04 beamline at Diamond with access through the GCRF START grant.

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

Commenting on the research outlined above, Prof Trevor Sewell, Lenye’s supervisor, said,

“The work of the last 30 years has provided a wealth of knowledge about the structures, occurrence and chemistry of members of the ubiquitous nitrilase superfamily of enzymes. This has led to their widespread use as industrial enzymes and a recognition that some superfamily members are potential drug targets. Even so, our understanding of their mechanism and our ability to introduce desirable properties through design is very limited. Lenye’s work seeks to surmount the barriers, leading to the ability to enhance at least one property of the cyanide degrading nitrilases, the thermostability, by design and then verify that the desired goal has been achieved experimentally using CryoEM and differential scanning calorimetry.”

Find out more about the UN’s Sustainable Development Goals here

About Lenye Dlamini

Lenye Dlamini was born and raised in Mbabane, the capital city of Swaziland, which is also where she received her primary and high school education. Lenye was inspired into science at high school through her biology and chemistry teacher who, Lenye says, saw the potential in her and motivated her to work extra hard. Prior to embarking on her PhD studies, Lenye’s tertiary education was at the University of Pretoria in the laboratory of GCRF START Co-I, Prof Wolf-Dieter Schubert. Lenye is currently a PhD candidate in Medical Biochemistry in the Structural Biology Research group, Department of Integrative Biomedical Sciences, Faculty of Health Sciences at the University of Cape Town, South Africa.


[1] Mulelu, A. 2017. Factors involved in the oligomerisation of the cyanide dihydratase from Bacillus pumilus C1. University of Cape Town. http://hdl.handle.net/11427/24446

2 Sewell, BT, Frangakis, A, Mulelu, A and Reitz, J. (2017). The structure of the cyanide dihydratase (CynD) from Bacillus pumilus. Acta Cryst.  A73, C1296. DOI: 10.1107/S2053273317082791

From medicinal chemist to protein crystallographer – Anton Hamann’s story

From medicinal chemist to protein crystallographer, Dr Anton Hamann has made remarkable strides in structural biology despite many challenges. These achievements he attributes to new doors of opportunity which have opened as a result of GCRF START grant funding for his role as a Post-doctoral Research Fellow at Stellenbosch University, South Africa – a role which has changed his life and career in many ways.  Although possessing “no previous experience” (as he puts it) in the particular techniques and skills required, Anton has not only retrained into a new field of science in a short space of time, but he has also learnt world-class techniques scarce in Africa, and now develops small and novel molecule inhibitors to combat diseases. Here is his inspiring story in his own words….

My love for science and medicine

My name is Anton Hamann and I grew up on the outskirts of Cape Town, in the Western Cape of South Africa. I was diagnosed with severe hearing loss in both ears with no possibility of recovering the loss. Despite this, from a very young age, I enjoyed science and building contraptions. I was also a bookworm and always enjoyed visiting the local library. My high school science teacher was extremely passionate in chemistry and motivated me to pursue a degree in chemistry. As a result, I decided to pursue a career in science, starting with a BSc degree in Chemical Biology at the University of Stellenbosch. After that, I started with my postgraduate studies (BSc Honours, MSc and PhD) with organic chemistry as my discipline.

Dr Anton Hamann, GCRF START Post-doctoral Research Fellow at Stellenbosch University, South Africa. Photo credit: Blake Balcomb. ©Diamond Light Source

I was always fascinated in medicine and how it affects our bodies and staves off diseases. It was questions like – What molecules are involved and how do these molecules change the biology in our bodies? How can we use these molecules to combat diseases? Can we cure these diseases with better molecules? What are these molecules? –  that intrigued me.

This prompted me to do research in the field of medicinal chemistry which is a multi-functional field with various applications in drug discovery, drug design, synthetic chemistry, and protein molecular modelling. During my MSc and PhD, I focused on developing drugs with better medicinal properties for the treatment of malaria and Alzheimer’s disease. Over the course of time, I have synthesised several molecules that have the potential to be further developed into medicinal drugs for malaria and Alzheimer’s disease. This has resulted in two publications for my work in malaria (South African Journal of Chemistry, 2013, 66, 231-236 and Bioorganic & Medicinal Chemistry Letters, 2014, 24, 5466-5469) and we are currently in the process of publishing the Alzheimer’s disease results in a peer reviewed journal.

Re-training as a protein crystallographer

After my PhD, I decided to carry on with my research in the field of medicinal chemistry but was looking for a new challenge. This is when I joined Prof. Erick Strauss’ research team as a post-doc to explore the possibilities of developing novel antibiotics for Staphylococcus aureus. This is also where I heard about the GCRF START grant for the first time.

Although GCRF START’s life sciences focus is mainly structural biology, a field in which I possessed no previous experience, I was determined to learn as much as possible and be retrained as a protein crystallographer. This is where the START grant made a significant impact on me, not only fully funding my role as a post-doc but also giving me opportunities to attend conferences and workshops in South Africa and UK, and to hone my skills as a protein crystallographer. As I’ve progressed during my post-doc, I have become a better medicinal chemist with the new skills that I have developed in the field of structural biology thanks to the opportunities provided by the GCRF START grant.

Dr Anton Hamann using the ÄKTA Prime FPLC to purify his protein from a lysed cell media at Stellenbosch University’s Biochemistry Department. Photo credit: Dr Blake Balcomb. ©Diamond Light Source

The GCRF START grant has given me an incredible opportunity to visit XChem twice for two weeks in total at the UK’s national synchrotron, Diamond Light Source (Diamond), to carry out X-ray crystallographic fragment screening experiments. I’ve gained valuable experiences from Dr Romain Talon and Dr Alice Douangamath and these visits also introduced me to a new field of high-throughput screening where the workflow is almost fully automated. I’ve had access to Diamond’s state-of-the-art equipment including the I04-1 beamline. During this time, I’ve had the opportunity to soak my protein crystals with hundreds of different fragments to identify potential small molecules that bind to the enzyme. These molecules can then be expanded into larger molecules with higher potency and act as antibiotics for Staphylococcus aureus.

To date I’ve used the I03, I04 and I04-1 beamlines at Diamond to obtain diffraction data of my Staphylococcus aureus protein crystals which was extremely valuable to my research. I have also attended a CCP4 (Collaborative Computational Project Number 4) workshop in York in the UK, where I learned how to process the diffraction data to solve the crystal structures. GCRF START is one of the CCP4 workshop partners.

Another benefit of the GCRF START grant has been the fruitful collaborations and relationships that I have built with other South African and British structural biologists who have significantly aided my career progression. In addition, I have learned valuable tips and skills from Romain and Alice at Diamond. They gave me insights on how to achieve optimal crystals and what to do if your proteins do not crystallise. They have been incredible in assisting me with the XChem project.

Commenting on Anton’s achievements and the support of the GCRF START grant, Prof. Erick Strauss said,

“I’ve always personally been of the opinion – and this is especially relevant in the South African context – that a scientist with multiple skill sets and the ability to transition easily between fields is more likely to make a deep impact. It was with this in mind that I was really happy to welcome Anton into my group: as a skilled synthetic chemist I was certain that he would be more than able to take on protein crystallography to bridge the chemistry/biology divide. And without the GCRF START grant, this would not have been possible – we are extremely thankful for this support.”

Acknowledgements  

I would like to thank Prof. Erick Strauss, who is a GCRF START Co-Investigator, for taking a gamble on someone like me who is an organic chemist and not a biochemist! The effort he was willing to put into me and this project is highly appreciated. I couldn’t have asked for a more invested supervisor. I am also grateful to my lab mates, Dr Blake Balcomb (GCRF START-funded Post-doctoral Research Fellow) and Konrad Mostert, for teaching me the nuts and bolts of protein chemistry. I am also thankful to Dr Carmien Tolmie (previously a GCRF START-funded Post-doctoral Research Fellow) and the other GCRF START Co-Investigators, Prof. Trevor Sewell, and Prof. Wolf-Dieter Schubert for their work behind the screen to keep things running smoothly. Lastly, a big thank you to the people at Diamond for making this a reality.

Read about the UN’s Sustainable Development Goals for Health and Wellbeing here.

MSc student lauded for world-class HPV research on International Women’s Day

On International Women’s Day (today – 8th March), we highlight the achievements of Melissa Marx, an MSc medical biochemistry student in the University of Cape Town’s (UCT) Faculty of Health Sciences (FHS), who is conducting ground-breaking research in the field of cervical human papillomavirus (HPV) with the assistance of the GCRF START grant. HPV is the cause of most cervical cancer cases amongst women worldwide. Melissa’s research into HPV, which forms part of a larger departmental programme, was funded by the GCRF START grant which provided access to the UK’s world class national synchrotron, Diamond Light Source.  

Marx’s research focused on visualising the effect of an enzyme found within the reproductive tract on the structure of the virus, as it occurs during the infection process. To achieve this, she and fellow researchers studied HPV pseudoviruses (non-infectious and synthetic viruses) using laboratory-based techniques, structural biology and computational work. 

Melissa hopes that her findings will set a strong foundation as scientists work towards discovering preventative and therapeutic options for HPV infection to decrease the high burden of HPV infection in South Africa, on the continent and around globe. Cervical cancer is the fourth most common cancer among women worldwide. 

“Without the help of the GCRF START grant, much of my research would not have been possible. The grant enabled me to apply cutting-edge structural biology techniques to gain insights into the structure of HPV,” she said.  

“I was also incredibly fortunate to have collected data at the Electron Bio-Imaging Centre at Diamond Light Source in the United Kingdom. This was only possible with funding from the GCRF START grant.” 

Read the full story here 

Melissa Marx, MSc medical biochemistry student in the University of Cape Town’s (UCT) Faculty of Health Sciences. Melissa’s research in the field of cervical human papillomavirus (HPV) is assisted with funding by the GCRF START grant. Photo supplied by Melissa Marx.

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.