GCRF START

“Now we have built up the base for computer modelling here in Southern Africa, the GCRF START grant will help us take experimental science, simulations and knowledge exchange even further, building on 30 years of successful collaboration between African and UK scientists to address global energy and climate challenges.” 

Prof. Phuti Ngoepe, GCRF START Co-Investigator, University of Limpopo, South Africa 

Long-standing collaborations with the UK research community have demonstrated the mutual positive impact from partnerships which benefit from unique African perspectives. Spanning more than 30 years, one such partnership is the research collaboration between Professor Phuti Ngoepe, Director of the Materials Modelling Centre at the University of Limpopo (UL) in South Africa, and Professor Sir Richard Catlow, Professor of Catalytic and Computational Chemistry at the University of Cardiff and Professor of Materials Chemistry at University College London in the UK.  

Initially funded by The Royal Society, London (UK), and South Africa’s National Research Foundation (NRF), the collaboration between Prof. Catlow and Prof. Ngoepe has afforded many UK and African scientists opportunities over the years to share skills, build capacity, and get involved in diverse and sustainable projects related to energy storage, mineral processing and alloy development, including recently, with the GCRF START grant, of which both Prof. Ngoepe and Prof. Catlow are Co-Investigators. 

With the GCRF START grant, Prof. Catlow and Prof. Ngoepe are shaping a future legacy built on shared knowledge and past achievements, where emerging scientists in Africa and the UK are trained in the latest synchrotron techniques, and experimental synchrotron science complements cutting edge simulations.  

The building of a legacy: UK-Africa scientific collaboration and capacity building 

The collaboration between Prof. Catlow and Prof. Ngoepe is notable for its many achievements with fruitful outcomes that have been mutually beneficial, not only for the research interests of both scientists, but also in the building of strong teams of simulations experts and improvements in computer modelling and experimental science in Africa and the UK. This has been demonstrated right from the beginning of the partnership, Prof. Ngoepe says, where UK methodologies in energy material simulations were influenced by knowledge exchange between South Africa and the UK.

“At the start of the collaboration, South African minerals were not that “friendly” to the existing modelling techniques in the UK, especially the minerals that work,” Prof. Ngoepe recalls. “This prompted us to introduce and improve the methodologies of the simulations to address these challenges, which helped the simulations in the UK to advance to where they are today. We jointly extended this experience to other African countries, with science advocacy roles forged in institutions across the continent. Richard and I went to Ghana together and to Botswana, and with the experience we built were able to reach out and develop capacity in these countries in the area of simulations. Because of this common experience, when South Africa established its National Centre for High Performing Computing, we were able to bring other African countries on board.”

Technology development has marched forward at lightning speed since then and the collaborative work of the two scientists has diversified successfully into many interesting applications with effective capacity building leading to several researchers involved in the collaboration holding prominent positions in South Africa. A particular highlight is Prof. Ngoepe’s success in setting up a leading Computational Materials Modelling Centre (founded in 1996) at the University of Limpopo – a university that was disadvantaged in the pre-1994 Apartheid dispensation and historically under-resourced for research and innovation. Located in a mainly rural region, the University of Limpopo still predominantly caters for students from disadvantaged backgrounds and rural areas.  However, over recent years, it has developed successful capacity building approaches relevant to many developing countries and from which the group at UL’s Materials Modelling Centre has benefitted.

Through the combined efforts of Prof. Ngoepe, Prof. Catlow and others, new concepts such as Post-Doctoral Researchers and Research Associates were introduced into the Centre’s institutional environment in addition to the advantages of linking researchers to relevant practical initiatives and extending research to address challenges of those programmes, as well as assistance with basic needs such as accommodation and tuition costs. The result has been the promotion of a critical mass of Master’s and PhD students from previously disadvantaged backgrounds through the retention of good students with high computing skills who might otherwise have left research due to financial and other constraints. Today, UL’s Computational Modelling Centre is considered “one of the leading centres within South Africa’s Higher Education landscape where computer modelling is conducted on material for a broad range of industrial applications, such as energy-storage devices, minerals and metal alloys.[1]”

Another achievement of the collaboration between the two scientists is the successful programme of joint conferences at the University of Limpopo and exchange visits by South African and UK students, which has helped shape knowledge and practice in both countries in fundamental ways. “In extending the cyber infrastructure capacity, relations that were formed during the exchanges with fellow postgraduate students in the UK over many years, have and still help to facilitate knowledge, practices and expertise in this ever-expanding field,” Prof. Ngoepe explains.

“It has been hugely rewarding working with Phuti and colleagues and with other African scientists over the last 30 years,” says Prof. Catlow, “I first visited the University of the North (now University of Limpopo) in autumn 1994. I met Phuti and a young colleague working enthusiastically in a small computer lab with one Silicon graphics machine. Over the ensuing decades we have seen develop, from this very modest beginning, a strong and successful centre that has not only produced excellent science but has populated, universities and research centres with its graduates. And I am very pleased and proud that UK scientists were able to contribute to this remarkable achievement.”

Dr Happy Sithole is the Director of South Africa’s Centre for High Performance Computing (CHPC) and Center Manager of the South African National Integrated Cyberinfrastructure System (NICIS). His story, says Prof. Ngoepe, is “a fantastic example of the way this international exchange and collaboration can have a lasting impact”. Dr Sithole obtained his PhD at the University of Limpopo under Prof. Ngoepe and Prof. Catlow’s UK-South Africa collaborative exchange programme early on in his career, the impact of which he describes below.

“I received my PhD through this collaboration, which made it possible to work with various experts in the UK, such as the late David Pettifor, Steve Parker and Kate Wright,” Dr Sithole recalls. “What this really presented was infinite imagination of problems that could be solved. The various expertise enabled me to cover all different aspects of mineral processing and not limiting me to only understanding the properties of materials. I have managed to expand my initial PhD thoughts into what now could be called the bedrock of mineral processing through modelling and simulation, backed by experimental proof. This also presented an opportunity for UK institutions to expand their software and tools to study new problem areas that were proposed by the Materials Modelling Centre in South Africa. I have seen the evolution of METADISE driven by the continued surface requirements of Platinum Group Metals. I am currently heading the National Integrated Cyber-Infrastructure in South Africa, which thrives through collaboration with UK institutions, and contributes to other activities in the UK. It is a mutual benefit between the two countries.”

Dr Sithole has taken teams of scientists and won awards at international meetings and continues to maintain the partnerships he formed with scientists in the UK, which have since deepened and expanded.

Extending the legacy with GCRF START – innovative science and a new generation of science leaders

Building on this legacy, the GCRF START grant has given Prof. Ngoepe and his group momentum to set up new, ground-breaking projects that will radically increase and speed up what the group is able to achieve, providing the means to train and mentor a new cohort of emerging scientists skilled in the latest experimental and theoretical techniques. One of these initiatives aims to advance the group’s research on battery cathodes through the setting up of a new Li-ion Battery Cathode Synthesis Laboratory at the University of Limpopo (currently being commissioned after an initial delay due to the Covid-19 lockdown). The Li-ion Battery Cathode Synthesis Laboratory will provide the group with their own samples to be studied using the UK’s Diamond synchrotron with access provided by the GCRF START grant. The ultimate goal is to contribute to global efforts to produce safe, cheap, ‘green’ batteries with a longer life cycle, increased storage capacity, a wider optimal temperature operating range, and higher power output.

High energy density batteries are central to development of electric vehicles, solar energy storage and electricity utility backups – crucial in mitigating adverse effects of global climate change. Currently, computational modelling studies of manganese-based battery cathodes are explored such as the spinel lithium manganese oxides and manganese rich NMCs of these. Predicting structural stabilities is vital, especially during charging and discharging in order to ensure long life of the batteries. These predictions guide where to put emphasis on experiments, and aid in the interpretation of results. “For this, access to the Diamond synchrotron with the GCRF START grant will be of enormous value,” Prof. Ngoepe explains, “bringing many new dimensions to what we can do within our group.”

“The START grant will enable innovative research insights emanating from comparison of the simulations done by Prof. Ngoepe’s group at the University of Limpopo’s Materials Modelling Centre with synchrotron experimental results,” says Prof. Catlow. “Synchrotron science is an absolutely key area of contemporary science across the board and GCRF START is producing a trained workforce in this field. It is the development of people with expertise in leadership which makes it possible to develop cutting edge facilities and innovative science. We hope that the development of these skills will help to provide support and momentum for the African Light Source project which aims to develop a synchrotron facility on the continent.”

In terms of investing in people, GCRF START grant acts like a catalyst in the training of emerging young scientists to be future science leaders. This is made possible through exchanges and workshops, access to world class equipment and facilities, and mentoring by experts, along with financial and practical support. Within Prof. Ngoepe’s group at UL’s Materials Modelling Centre, there are more than ten students being equipped in this way through exploring simulations of various energy storage areas, ranging from cathode, anode and beyond to lithium-ion battery materials.

Dr Clifton Masedi is a START Post-Doctoral Research Fellow working together with postgraduate students in the Materials Modelling Centre alongside Dr Noko Ngoepe who oversees experimental aspects of the synthesis of cathode materials earmarked to be linked with the Diamond synchrotron. With a background in computational modelling of energy storage materials, Dr Masedi is investigating stabilities of NMC cathode materials and lithium sulphur for batteries using universal cluster expansion methods and will initially use the samples grown from the synthesis laboratory at UL for synchrotron studies and compare them with simulations. By bringing students in the Materials Modelling Centre to work closely with Dr Masedi, the plan is to expose more students to synchrotron science.

“With the GCRF START grant, the process of combining synchrotron science with computer modelling/simulations, enables a critical number of people to be trained in foundational and synchrotron techniques, whilst doing very interesting science. Such exposure is motivational and extends scientific and cultural outlook,” says Prof. Ngoepe. “The goal with the GCRF START grant is to extend these insights to more students in the future, thus developing a trained workforce in contemporary scientific techniques while continuing our collaboration with the UK for generations to come.”

This approach is whole-heartedly endorsed by Dr Sithole who points out that, in the past, Prof. Catlow and Prof. Ngoepe’s efforts followed a similar path, leading to the successful, sustainable impact seen today.

“In line with linking experimental facilities such as the synchrotron to modelling and simulations, I believe this is one of the core ingredients of the success of your previous collaboration. Embedding Human Capital Development in this process cannot be over emphasised, as this is the heart of sustainability of the collaboration,” says Dr Sithole. “We have learnt this through the collaboration under the National Research Foundation and The Royal Society, where a strong team of simulation experts was built in South Africa – in particular at the University of Limpopo – and which elevated the institution’s research capacity now visible through the Materials Modelling Centre. The linkages built during this period continue to function within institutions in the UK and South Africa. I am looking forward to participating in this [GCRF START] collaboration and believe South Africa will be able to bring to the table computational resources and skills which were built through the initial collaboration and further expanded to the bulk of the African continent, making this GCRF START project an even better collaboration.”

About Professor Phuti Ngoepe

Prof. Phuti Ngoepe is a GCRF START Co-Investigator and Senior Professor and Director of the Materials Modelling Centre at the University of Limpopo in South Africa, where research focuses on the prediction of the properties of minerals, light and precious metal alloys, and energy storage materials used mostly in lithium-ion batteries. Prof. Ngoepe’s team has contributed novel work on the simulated synthesis of nanostructures for lithium-ion and newer lithium-air batteries. Simulations are used to predict the performance of such structures, by calculating their voltage profiles, microstructures and mechanical properties. A Founder Member of the Academy of Science (South Africa), Prof. Ngoepe holds the South African Research Chair (SARChI) on Computational Modelling of Materials and has served on the boards of a number of prominent science councils including the National Research Foundation (South Africa), Mintek and the Council for Geosciences, amongst others. Prof. Ngoepe has participated in many science strategy committees and reviews of government institutions and programmes, and in bilateral science and technology missions which have taken him, among others, to the USA, Russia, Japan, China and countries in the European Union. In 2008, Prof. Ngoepe was awarded the South African Presidency’s highest honour – the Order of Mapungubwe Silver for “excellent achievements in the field of the natural sciences and contributing to the development of computer modelling studies at the University of Limpopo”[2]. Click here for a full biography.

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

About Professor Sir Richard Catlow

Prof. Sir Richard Catlow is Foreign Secretary and Vice President at The Royal Society, London (UK), Professor of Catalytic and Computational Chemistry at Cardiff Catalysis Institute (UK) and Professor of Chemistry at University College London (UK), and a GCRF START Co-Investigator. He is also a co-founder of the UK Catalysis Hub. Professor Catlow develops and applies computer models to solid state and materials chemistry — areas of chemistry that investigate the synthesis, structure and properties of materials in the solid phase. Richard’s work has provided insight into mechanisms of industrial catalysts, especially involving microporous materials and metal oxides, as well as how defects — missing or extra atoms — in the structure of solids can result in non-stoichiometric compounds. “Simulation methods are now routinely used to predict the structures of complex solids and silicates, respectively, thanks to Richard’s demonstrations of their power. By combining powerful computational methods with experiments, Richard has made considerable contributions to areas as diverse as catalysis and mineralogy.[3]”

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

About Dr Happy Sithole

Dr Sithole is the director of the Centre for High Performance Computing at South Africa’s Council for Scientific and Industrial Research (CSIR) and Centre Manager of the South African National Integrated Cyber-Infrastructure System (NICIS). He completed his PhD at the University of Limpopo focusing on electronic and atomistic simulation of iron sulphides. Dr Sithole has applied high-performance computing to solve problems in mining industries and nuclear power plant designs. He sits on various high profile local and international high-performance computing committees.

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

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

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

“Over the past two years, being involved in the GCRF START grant has allowed me to mature and to become much more independent as a scientist.”  

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

The molecular workings of the natural world have always interested me, especially how we can use these processes to sustainably improve human health and agriculture. My name is Carmien Tolmie and I grew up in the small city of Bloemfontein, in the Free State province of South Africa. From a young age, I enjoyed maths, science and languages, and I participated in various extracurricular academic activities in STEM. As a result, I decided at an early age to pursue a career in science, starting with a BSc degree in Molecular Biology and Biotechnology at the University of Stellenbosch, and returning to Bloemfontein for my postgraduate studies (BSc Honours degree, MSc and finally PhD) at the University of the Free State (UFS), where I chose Biochemistry as my discipline. 

Structural Biology is an incredibly powerful and multi-functional field with various applications in human health, agriculture and sustainable ‘green’ chemistry (environmentally friendly chemistry). Passionate about addressing the challenges I see in Africa, I was motivated to undertake my PhD with Prof. Dirk Opperman who is a GCRF START Co-Investigator (Co-I) in UFS’s Biocatalysis and Structural Biology research group, working on enzymes (proteins that act as biological catalysts) from Aspergillus flavus. The Aspergillus flavus fungus grows on agricultural crops, produces cancer-causing compounds and can also cause infectious fungal disease. Studying the atomic structures of proteins from fungi like the Aspergillus flavus reveals a wealth of information, such as how the three-dimensional structure looks and changes during the chemical reactions it catalyses, the possible mechanism of how the protein works, and how it binds to small molecules. If the protein is a drug target, the structure can be used in Structure-Based Drug Discovery to develop new medications, ‘green’ pesticides for agriculture, and other applications.  

Passing on the love of learning to other young scientists 

I love learning and discovering new things, working in the lab, as well as passing on the knowledge to others. Therefore, I decided to build a career in academia with a focus on Structural Biology. I have recently been appointed as a full-time academic in UFS’s Department of Microbial, Biochemical and Food Biotechnology (January 2020) where I have a joint research and teaching position as Lecturer in Biochemistry.  In my new fungal drug discovery projects, which I have just started (delayed because of Covid19 lockdown), I am the main Principal Investigator (PI) in collaboration with Prof. Opperman and Prof. Martie Smit. 

My new research projects will look specifically at developing inhibitor compounds against fungal metabolic targets with the aim of discovering new antifungal compounds.  Existing anti-fungal medication and pesticides have been so widely used that fungi have evolved and developed ways to combat the anti-fungals, thereby becoming drug resistant. Our research may help in the future to develop sustainable solutions through novel antifungal drugs to improve the health, wellbeing and prognosis of people who suffer from infectious fungal disease, particularly immune-compromised patients, where fungal infections can cause serious health complications and can be life threatening.  

To conduct the research, I will use the structure-based drug discovery method of X-ray crystallographic fragment screening at the UK’s national synchrotron, Diamond Light Source (Diamond). This method uses protein crystals of the target enzyme to identify small molecule fragments that bind to the enzyme. These fragments are then elaborated into larger molecules with higher potency, which will hopefully not only inhibit the specific enzyme, but also the growth of pathogenic fungi. I was introduced to the concept and power of fragment screening techniques during GCRF START meetings and learnt more about the experimental workflow of XChem and the I-04 beamline during my research visit to Diamond Light Source in the UK last year, which inspired me to embark on XChem projects for antifungal drug discovery.  

Investing in African Early Career networks through GCRF START grant 

“Carmien is not only passionate about Structural Biology, but also teaching. She has been a vital part of START, helping and teaching the postgraduate students not just in our lab, but also reached out and helped other GCRF START groups in South Africa.”

 Prof. Dirk Opperman, University of the Free State 

Being involved in the START grant has made a very concrete contribution to my career as a young scientist. At the beginning of the START project, I was a PhD student with Prof. Opperman. The START grant has contributed to the running cost of our laboratory, funded my postdoctoral salary for 2019, as well as my travel cost of attending a CCP4 workshop in Brazil (2018), the Biophysics and Structural Biology at Synchrotrons workshop, and various START meetings. The grant also enabled and funded my research exchange to the UK last year (2019). Through START, we have met numerous top-notch scientists that can advise us on our experiments. We have START meetings for early career scientists, both in the Structural Biology and Energy Materials strands of the START project. We routinely collect data with other members of the South African Structural Biology Consortium at Diamond (various universities and START collaborating laboratories), albeit through remote access –  a process that was greatly improved by a Data Collection Workshop run by Diamond’s beamline scientists in Pretoria last year, and which enhanced our data collection skills and deepened our relations within the network established by START.  

Interestingly, this international collaboration has been instrumental in establishing a network of early-career structural biologists in South Africa, including postgraduate students and postdoctoral researchers. Getting to know peers who are working in Structural Biology, and who are using the same techniques as I am, and who have similar research interests has provided a feeling of connectedness. These projects are often very demanding and having the support and motivation of a friend who has encountered similar setbacks (or being that friend to someone else) can really help one endure in difficult times. My hope is that this network will be the basis for many future collaborations.  

Exposure to international research collaborations and facilities  

GCRF START has exposed me to many esteemed international scientists and facilities. The START events have introduced me to scientists at Diamond who are very supportive and who have invested in both the START project and the development of the people involved in the project, such as START Co-I, Prof. Frank von Delft, who has research groups at both Diamond and the Structural Genomics Consortium at the University of Oxford. I was hosted by the Structural Genomics Consortium for a two-month research exchange last year to develop new experimental skills and this kind of exposure has greatly improved my skills and the way I think about my research. 

At the time of writing, I am currently involved in organising a crystallographic data processing workshop in South Africa – the first of its kind to be held on the continent – with START and CCP4. The workshop was supposed to be in April of this year (2020) but had to be postponed because of the Covid19 pandemic. I am one of the main local organisers, and this has given me the opportunity to improve both my grant-writing skills and organisational skills. In addition to funding by CCP4 and START, we have secured funding from the International Union for Crystallography, the International Union for Pure and Applied Physics, the National Research Foundation of South Africa, and the University of Cape Town. 

Gaining the competitive edge! 

Over the past two years, being involved in the grant has allowed me to mature and to become much more independent as a scientist.  My appointment as a Lecturer in Biochemistry means starting with my own, independent research projects in Structure-Based Drug Discovery, which is very exciting, and scary at the same time! I will be responsible for the second-year undergraduate Biochemistry module – Enzymology and introduction to metabolism.  Although this is a difficult year to start teaching a module, I have a great support system at the department. I truly believe that the experience and exposure of START gave me a competitive edge in being selected for the position, and I am very grateful for this opportunity.  

“The opportunities that were afforded to Carmien through the GCRF START grant enabled her to transition to academia. For the momentum we have gained through the grant to continue, we must transition our START Post Graduate Research Assistants into permanent academic positions. This allows us to retain the ‘critical mass’ required for structural biology to be successful in South Africa.”  

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

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

Acknowledgements 

I would firstly like to thank Dirk for the motivation, support and academic mentoring throughout the years; I would not have been the researcher I am today without him. I would like to thank Prof. Trevor Sewell (Director of the Aaron Klug Centre for Imaging and Analysis, University of Cape Town), Dr Ruslan Nukri Sanishvili (formerly of Argonne National Laboratory, Chicago, USA), Dr Gwyndaf Evans (Deputy Director Life Science, Diamond Light Source), Dr Dave Hall (MX Group leader, Diamond Light Source), and the CCP4 staff for their help in organising the CCP4 workshop. I would also like to thank Prof. Frank von Delft (Diamond Light Source, University of Oxford) and Dr Nicola Burgess-Brown (University of Oxford) for hosting me in their research groups. Finally, I would like to thank the University of the Free State and especially Prof. Martie Smit (HOD, Dept. of Microbial, Biochemical and Food Biotechnology) for giving me the opportunity to further my academic career.  

Tolmie C, Do Aido Machado R, Ferroni FM, Smit MS and DJ Opperman (2020). Natural variation in the ‘control loop’ of BVMO_AFL210 and its influence on regioselectivity and sulfoxidation. Catalysts 10(3): 339. doi: 10.3390/catal10030339 (Impact factor 3.444): https://www.mdpi.com/2073-4344/10/3/339 

Carmien’s profile on Research Gate Profile

“I think we, as African scientists, have a lot to offer. We are very connected and very close to the problems of the world. On a daily basis, we witness many of the global challenges first-hand and see the impact of diseases like HIV/AIDS, TB, Malaria, cancers and other communicable, as well as non-communicable diseases. We can see directly how our research can be life-saving. This is a big motivator!” 

Melissa Marx, University of Cape Town, South Africa 

To me, the GCRF START grant means the ability to learn new techniques which I can apply in my research on the human papillomavirus (HPV) 16 pseudovirions (PsVs) at the University of Cape Town (UCT). I’m using the structural biology technique cryo-electron microscopy (cryo-EM) to image HPV16-PsVs particles in order to obtain a better idea of the entry mechanisms used by the virus to infect host cells. With the help of the START grant, I can use techniques for research that could potentially contribute to the development of inhibitors for HPV infection, thereby decreasing HPV-associated cancer incidence down the line. This is really exciting and topical because cervical cancer – almost always caused by oncogenic HPV infection – is one of the most common cancers in women globally and the HPV is the second most frequent cause of cancer among women in Africa and in my own country of South Africa. My research and the START grant are therefore very important to me personally, as well as for women in Africa in general.  

As a ‘newbie scientist’ in the early stages of my career, it is important to be exposed to different techniques that we wouldn’t normally be exposed to here in Africa. In my undergraduate degree, I had almost no exposure to electron microscopy and computer software in general. Fast forward to the present as a first year MSc student, and after only one year of experience in this field (and lots of help), I’ve managed to make three reconstructions of HPV particles using two different reconstruction programs and have made large numbers of grids on which we mount the samples! Within South Africa, there isn’t a lot of information about cryo-EM and other techniques we need to use for our research. Through the grant, I have been able to learn things like negative staining, vitrification, sample purification, sample preparation, and data analysis using RELION, and I even had the opportunity to go overseas to visit the UK’s national synchrotron, Diamond Light Source (Diamond). 

Why developing Inhibitors for HPV could be the way forward 

“Melissa’s project is the result of a fruitful collaboration with the Electron Microscopy Unit at the University of Cape Town which adds exciting new approaches to study and target viral entry mechanisms.” 

Dr Georgia Schäfer, University of Cape Town, South Africa 

Human Papillomavirus (HPV) is one of the most commonly diagnosed sexually transmitted viruses worldwide, and infection with high risk types has been linked to several cancer types, most notably cervical cancer, as mentioned above. In Africa, an estimated 372.2 million women aged 15 years and older are at risk of developing cervical cancer; every year, 119,284 women across Africa are diagnosed with cervical cancer and 81,687 women die from the disease, as reported by the HPV Centre report on HPV in Africa, 2019.  In my own country of South Africa, cervical cancer is the first most common female cancer in women aged 15 to 44 years and one of the leading causes of cancer related deaths [1-6]. Although HPV vaccinations exist and are safe, these vaccines are only protective to HPV uninfected adolescents, making them ineffective for persons already infected with HPV [7,8].  

The vaccines are also relatively expensive and need repeat doses [7,9,10]. This creates a difficult situation for many people, who may not be able to afford repeat treatments or do not have easy access to health care facilities. In addition, rural communities in South Africa are largely unaware of HPV infection as a risk factor for cervical cancer, which has made vaccine distribution ineffective, with little of the South African population vaccinated between 2009 and 2014 [11]. Developing medication to prevent HPV infection by blocking the entry of HPV into susceptible human cells could be an alternative to vaccination, and another opportunity to reduce the amount of HPV associated cancers within South Africa and worldwide.  

In our laboratories at the University of Cape Town we have identified two human proteins, surfactant protein A (SP-A) and vimentin, which decrease HPV infection by modulating viral entry into susceptible cells [12] or by activating the innate immune system, respectively. This research took place in UCT’s Electron Microscope Unit at the Aaron Klug Centre for Imaging and Analysis and Division of Medical Biochemistry and Structural Biology (Institute of Infectious Disease and Molecular Medicine). To determine which portions of these two proteins interact with HPV, electron microscopy imaging and 3D reconstruction studies of HPV particles pre-incubated with each of these two proteins are being conducted. From this, and further biochemical tests, we can determine the relevance of these interactions for HPV infection, with the potential to develop inhibitors for HPV infection of susceptible human cells.  

Using Diamond Light Source synchrotron to image our HPV samples 

In order to carry out this research access to state-of-the-art imaging equipment is vital. The GCRF START grant has made this possible, by providing our researchers and collaborators with access to the Electron Bio-imaging Centre (eBIC) embedded at Diamond Light Source.  My visit to the Diamond synchrotron to conduct experiments for my research took place from the 9 – 11 October 2019. We had done the sample preparation at the University of Cape Town and had shipped the HPV samples in liquid nitrogen to Diamond a few weeks previously, so they were there once we arrived. The HPV samples were loaded onto the Diamond M06 Titan Krios electron microscope with the help of eBIC staff before imaging them using the transmission electron microscopy (TEM) technique. 

Unfortunately, there are no equivalent facilities available on the African continent, and only a handful available worldwide, so I feel unbelievably fortunate to have been to Diamond – not just as someone from overseas on a tour but to have the experience as a researcher of working in and around such an innovative environment. The research and the equipment available are cutting edge and incredibly motivating to a young scientist. In addition to this, the scientists and staff are friendly and easy to engage with, and I found myself having conversations with researchers from all fields, not just biology.  

Having a central research hub with scientists from different academic backgrounds, such as the materials sciences, biology, physical sciences, chemistry and others, creates a co-operative space and is likely to benefit anyone who participates. Being at Diamond Light Source and the Harwell Campus made me realise that having such a research hub is essential to science, aside from making things easier logistically! It was an incredible experience to be at Diamond Light Source, and I don’t think I could thank everyone involved enough for all the support and guidance along the way.  

 Acknowledgements  

Most importantly, I would like to thank Dr Jeremy Woodward, who is a GCRF START Co-Investigator – for the time and effort he was willing to put into this project; I really wouldn’t be anywhere without him. I am also grateful to my supervisor, Dr Georgia Schäfer, for her help and encouragement, especially when producing the HPV16 particles at such short notice! I am also grateful to GCRF START Co-Investigator, Prof. Trevor Sewell, and Dr Andani Mulelu (previously a GCRF START-funded Postdoctoral Research Fellow), and to Dr Lubbe (currently a START-funded Postdoctoral Research Assistant); thanks also to Dr Sarron for all the advice and reassurance – which really helps! Lastly, I would like to thank the staff of the Electron Microscopy Unit at the University of Cape Town, especially Mohammed Jaffer, and the eBIC staff – James Gilchrist and Alistair Siebert – all of whom were very cheerful and accommodating when using the different microscopes. I even had a good enough sample for me to travel to Diamond, with the help of my two brilliant supervisors, Dr Georgia Schafer and Dr Jeremy Woodward, without whom, I might have been completely lost!  

My science career so far.. 

I’ve always had an interest in biology, and I was fortunate enough to have parents who encouraged my interest, although they didn’t always know what I was doing! I began my scientific journey by completing a Bachelor of Science at Stellenbosch University (South Africa) in biochemistry and physiology. I then moved to the University of Cape Town for my Honour’s and Masters’ degrees. I was exposed to structural biology during my Honour’s degree, but I was somewhat intimidated by all the physics and maths involved. So, I only became involved in structural biology during the first year of my Master’s degree, at the Biophysics and Structural Biology at Synchrotrons 2019 conference (Cape Town, South Africa). I am currently completing my MSc in Medical Biochemistry and Structural Biology, under the supervision of Dr Georgia Schäfer and Dr Jeremy Woodward, within the Electron Microscopy Unit at UCT. 

“The GCRF START grant has been a game-changer for young African scientists, particularly from underrepresented groups such as female, and black scientists, enabling them to enter the field of Structural Biology and thrive. This has been achieved by collaborations from Africa and the UK, outstanding workshops on research techniques, international conferences, symposia hosted in Africa, and the recruitment of African scientific officers and postdoctoral fellows.” 

Prof. Edward D. Sturrock, University of Cape Town, South Africa.  

GCRF START – belonging to a diverse group of African scientists  

My name is Lizelle Lubbe and I am a GCRF START Postdoctoral Research Fellow. My field of research is Structural Biology, which is a scarce skill in Africa with only a handful of scientists trained in single particle cryo-EM –  a cutting-edge technique for determining the structure of proteins. START provides me with the opportunity to learn from these science pioneers in Africa, as well as from experts in the UK by establishing networks for discussion and organising workshops for hands-on training. Furthermore, GCRF START provides us with the resources to conduct outreach, not only to make science accessible for the community but also to inspire the future generation of scientists. I find it very stimulating to be a part of such a diverse group of scientists who are all working together towards achieving common goals to uplift communities and find solutions to global challenges.  

Structural Biology combines concepts of Biology, Chemistry and Physics and therefore can be quite daunting to enter.  For example, the design of drugs for the treatment of disease requires one to understand how the disease develops, identify a drug target in this process, use medicinal chemistry to design a small molecule capable of blocking that target, and validate the process using structural techniques. Although this has traditionally been a more male-dominated field, the hardships endured by women in science throughout history have led to ground-breaking discoveries and a paradigm shift, so that today I have the privilege of doing my postdoctoral research using revolutionary techniques like cryo-EM. 

As a result of the GCRF START grant, I am funded to do my research which includes associated travel costs for data collection, access to mentoring from experts in their field, and the use of state-of-the-art equipment and facilities such as the UK’s national synchrotron, Diamond Light Source, and the GCRF START Centre for Excellence in the University of Cape Town’s (UCT’s) Aaron Klug Centre for Imaging and Analysis. START has made it possible to gain valuable and much sought-after experience and skills in biophysical and synchrotron techniques. 

Improving the health of patients with hypertension and other diseases 

My research is focused on a protein called angiotensin-converting enzyme (ACE) which is well-known for its role in blood pressure¹ regulation.  It is found in many organs throughout the human body where it catalyses a reaction to produce a peptide (string of amino acids) that causes constriction of blood vessels, thereby regulating blood pressure and circulation.  In some cases, however, this process goes awry, and the blood pressure becomes elevated, increasing the force of blood against the artery walls.  This condition is known as hypertension and typically does not produce any noticeable symptoms.  

According to the World Health Organisation, 1.13 billion people suffer from hypertension globally², with many countries in Africa³ experiencing the highest prevalence of hypertension in the world at 27% (WHO, 2019). Conditions caused by hypertension include stroke, heart failure, heart attack, kidney failure and loss of vision.  There are many risk factors to hypertension, and these include family history, increasing age, stress, being overweight/obese, a diet high in salt, smoking tobacco, drinking too much alcohol, and a lack of exercise.  Given the important role of ACE in blood pressure regulation, ACE inhibitors are commonly used in the clinic to effectively treat hypertension and heart/kidney disease.  The use of ACE inhibitors is unfortunately linked to the development of side effects in some patients.  It can be mild (loss of taste, skin rash or persistent dry cough) but also life-threatening in the case of angioedema. Angioedema is a condition where the patient develops severe swelling below the skin surface which can affect the throat, tongue and lips and obstruct the airway.  

I am motivated by the potential of the research we are doing to improve the lives of patients living with hypertension and other diseases associated with ACE by increasing our understanding of the disease-causing protein. This would ultimately allow us to design ACE inhibitors with less side-effects.  It is also very exciting to learn structural biology techniques such as cryo-EM and to help establish this expertise in Africa for the benefit of our community. By gaining valuable experience in the scarce field of Structural Biology, I hope to strengthen research in Africa and motivate others towards a career in science. 

Inspired into biochemistry – persistence pays off!  

The motivation I describe above started at a young age, and I was greatly inspired by my parents who both studied science – my mother studied Microbiology and my father, Mechanical Engineering. I grew up on a small farm outside Pretoria in the Gauteng province of South Africa and have been interested in the mechanism of action of therapeutic drugs from a young age.  Opportunities for women in science were scarce in the early 1990’s and my mother could unfortunately no longer pursue her career after my birth.  Her interest in the world of microorganisms remained, however, and inspired me to enter the field of Biochemistry where one could not only study microorganisms and other factors in relation to disease but also design therapies.   

I had very limited hands-on exposure to science at the farm school I attended.  My siblings and I spent many afternoons in the community library and at some point, I started reading encyclopaedias and became fascinated with science.  After that, I saved some money and bought myself a second-hand toy light-microscope which occupied me for hours.  However, these years were not without hardship. After obtaining his degree in Mechanical Engineering, my father single-handedly established a small business and it was very challenging to secure an income, so we were often left without certain essentials. Our school tuition was funded by government subsidies and as we could not afford private healthcare, I spent many school days in long queues since before the crack of dawn at the local District Hospital.  

During my final year at high school (matric), the Physical Sciences teacher told me about the field of Biochemistry and although my parents could not afford to pay for my tertiary education, I was determined to obtain a degree and arranged to get a student loan. Persistence paid off and I obtained my undergraduate Bachelor of Science (BSc) degree at the University of Pretoria majoring in Biochemistry and Chemistry in 2011.   

Great mentors – learning key Structural Biology techniques from GCRF START experts 

These challenges and hardships only cemented my determination to continue in the field I am passionate about and having experienced mentors has really helped. My PhD at the University of Cape Town was supervised and co-supervised by Prof. Ed Sturrock and Prof. Trevor Sewell, respectively.  They are both Co-Investigators on the GCRF START grant and, after finalising my PhD thesis, Prof. Sturrock offered me a GCRF START Postdoctoral Fellowship on a related research project in his laboratory. I started as a GCRF START postdoc in October 2018 and, in October 2019, I travelled to the UK to the Harwell Campus, and collected a dataset of ACE at the Electron Bio-Imaging Centre (eBIC) at Diamond Light Source using a Titan Krios transmission electron microscope with K3 detector. I am in the data analysis stage right now. 

Professor Sturrock⁴ is a leader in the design of anti-hypertensive drugs and was an excellent mentor during my BSc (Med)(Hons) in Medical Biochemistry (completed in 2012) and PhD in Chemical Biology (completed in 2018) studies.  He has taught me how to think critically about the problem at hand and to persevere despite the numerous setbacks one experiences as a scientist. For example, Structural Biology techniques such as X-ray crystallography, molecular dynamics (MD) simulations and cryo-electron microscopy (cryo-EM) are key to understanding proteins involved in disease and how to target them.  

However, because advanced Mathematics or Physics modules were not included in my undergraduate training, it was really difficult for me to learn the theoretical aspects of these techniques and how it is applied in practice. I am therefore very grateful for the START project which has given me the opportunity to learn from experts in the field of Structural Biology – experts such as Dr Jeremy Woodward and Prof.Trevor Sewell from the UCT Aaron Klug Centre for Imaging and Analysis. A further challenge throughout my PhD was my limited background in Computational Science.  The computer skills I learned from high school were very elementary which meant a particularly steep learning curve when I decided to use MD simulations to answer key research questions.  

Studying ACE for the future design of ACE inhibitors 

ACE is a dumbbell-shaped protein comprised of two domains (the N- and C-domain) which perform diverse physiological functions: the C-domain is mainly responsible for blood pressure regulation while the N-domain is important for regulating scar tissue formation. The main focus of Prof. Sturrock’s research is to design inhibitors that selectively bind to the N- or C-domain. Selectivity is very important since the side-effects associated with current ACE inhibitors are due to equal inhibition of both domains.  At the end of my BSc (Med)(Hons) year, Prof. Sturrock (in collaboration with Prof. Kelly Chibale at UCT) discovered a molecule (33RE) which binds with 1000-times greater affinity to the N-domain than the C-domain of ACE^5. N-selective ACE inhibitors are antifibrotic and as such, show potential for the treatment of fibrosis (excessive scar tissue formation).  X-ray crystallography was used to study the binding of 33RE to the N-domain but the reason for its selectivity remained a mystery.  One limitation of this technique is that it only gives you a static ‘snapshot’ of the protein’s structure while proteins are naturally very dynamic when in solution (as in the body).   

For my PhD research, I therefore decided to study ACE using MD simulations.  In this technique, the atoms in the crystal structure are allowed to move which can provide more insight into how the drug interacts with the protein.  My results were really interesting and showed that subtle amino acid differences between the two domains caused drastic changes in their dynamics and thereby, their affinity for 33RE⁶.   

GCRF START ensures the continuation of postdoctoral research 

As a GCRF START postdoc, I am continuing this research in collaboration with Prof. K Ravi Acharya⁷ at the University of Bath and we have recently discovered that these differences in dynamics also affect the binding and selectivity of ACE inhibitors from different classes^8 9.  This has great implications for the future design of ACE inhibitors and emphasizes the importance of using a range of biophysical techniques when studying proteins. The workshops funded by the GCRF START grant has equipped me with valuable skills and I am very excited to discover even more insight into the workings of ACE by applying these skills. 

The biggest challenge on my road to becoming a scientist has been financing ten years of tertiary study.  Although I was fortunate enough to receive merit and government bursaries to fund my PhD, I am still paying off the student loan from my undergraduate and honours years. Therefore, funding through the GCRF START grant has been invaluable, ensuring the continuation of my postdoctoral research.  

Commenting on Lizelle’s achievements and the impact of the GCRF START grant on emerging African scientists like Lizelle, Prof. Ed Sturrock said, 

“The GCRF START grant has had a significant impact on Lizelle’s career development, career opportunities and personal growth. Her progress with a very challenging research project and her involvement in other GCRF START activities, such as the START outreach project to uplift the community and promote science through art, bear testament to this. I have been enormously impressed by what Lizelle has achieved as a START postdoctoral research fellow in a relatively short period of time.”  

Read more about Hypertension here.

Read more about the UN’s Sustainable Development Goal 3 for Health and Wellbeing here.

Additional acknowledgements 

I am very grateful to Mrs Sylva L. U. Schwager (Chief Scientific Officer in Prof. Sturrock’s laboratory at the University of Cape Town) for her guidance and assistance with key experiments during my postgraduate and postdoctoral years.  

Related articles/publications 

• Cozier, G.E., Lubbe, L.*, Sturrock, E.D., Acharya, K.R. ACE-domain selectivity extends beyond direct interacting residues at the active site. Biochem J 477 (7), 1241–1259 (2020) https://doi.org/10.1042/BCJ20200060 
• Sturrock, E.D., Lubbe, L., Cozier, G.E., Schwager, S.L.U., Arowolo, A.T., Arendse, L.B., Belcher, E., Acharya, K.R. Structural basis for the C-domain-selective angiotensin-converting enzyme inhibition by bradykinin-potentiating peptide b (BPPb). Biochem J 476 (10), 1553–1570 (2019) https://doi.org/10.1042/BCJ20190290  

FOOTNOTES

[1]  https://www.healthline.com/health/high-blood-pressure-hypertension

[2] Hypertension, also known as high or raised blood pressure, is a condition in which the blood vessels have persistently raised pressure. For more information:  https://www.who.int/health-topics/hypertension/#tab=tab_1

[3] https://www.who.int/choice/demography/african_region/en/

[4]  http://www.idm.uct.ac.za/Edward_Sturrock

[5] https://doi.org/10.1042/CS20130403

[6] https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.13900

[7] https://researchportal.bath.ac.uk/en/persons/ravi-acharya

[8] https://doi.org/10.1042/BCJ20200060

[9] https://doi.org/10.1042/BCJ20190290

“The GCRF START grant has initiated a beautiful story and this story involves developing African scientists, especially in terms of Synchrotron Radiation Technology and Research. We hope to continue this highly fruitful collaboration for many years to come.”

Dr Ikechukwu Anthony Achilonu, Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand 

I love teaching and research, especially contributing towards human development through innovative research in medicine and biology. My research focuses on the Biochemistry and Structural Biology of druggable proteins of human Neglected Tropical Diseases (NTD’s) and ESKAPE pathogens (Healthcare Acquired Infections) at the University of the Witwatersrand’s Protein Structure-Function Research Unit (PSFRU). I owe my motivation for biochemistry to very good teachers and mentors from an early point in my education.  

I was educated to undergraduate level in biochemistry at Nigeria’s Abia State University, Uturu, Abia State and as an undergraduate, found pleasure in being taught by biochemistry lecturers who were able to ‘self-de-elevate’ and inspire us. These teachers were easy to have rapport with and I was able to extract as much as they could offer, both as my teachers, as well as my mentors and motivators. I remember Dr Okechukwu Ukairo, a young and admirable biochemistry lecturer who taught us carbohydrate metabolism and bioenergetics. His persona as a biochemistry lecturer and researcher enabled him to de-mystify what was a difficult course in biochemistry by being down to earth, but not to be trampled upon!  

Subsequently, I spent four years in Lesotho as an educator, teaching in secondary schools after briefly working as an analytical chemist at Lesotho Pharmaceuticals in Mafeteng. My desire to do my Master’s in Biochemistry was fulfilled, however, at the University of KwaZulu-Natal in Durban, South Africa, where I gained my PhD in 2008. Working with Prof Heini Dirr at Wits University (March 2009) strengthened my aspiration in Structural Biology and three years later, I joined The University of the Witwatersrand. Currently, I am a Senior Researcher and the Interim South African Research Chair (SARChI) in Protein Biochemistry and Structural Biology.  

When I look back at my career journey so far, it was the experience of having inspiring teachers and mentors that stayed with me to the present day and drives my vision as head of my group in teaching, supervising and mentoring the students on my watch. Therefore, the GCRF START grant with its emphasis on equipping and mentoring the next generation of scientists in Africa to tackle local and global challenges, means everything to me, especially in terms of structural biology. 

African scientists have a critical role to play in the search to solve Africa’s challenges 

“My vision is to see young people rise-up and flourish in the sciences on the African continent and apply the African, UK and global perspectives we share in the GCRF START network to the global challenges we face.” – Dr Ikechukwu Anthony Achilonu, Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand 

With the START grant I believe we can create a new narrative of excellence in African science and structural biology and fulfil our vision to equip our students in the latest techniques to solve our continent’s health, energy and socio-economic challenges. For example, at the PSRU, we have many gifted post-docs and undergraduates with the potential to go far and make a positive difference on our continent and beyond. I supervise 12 students (four PhD and seven MSc. students, and one Post-Doctoral Fellow), some of whom already benefit from the exposure to state-of-the-art synchrotron techniques at the UK’s national synchrotron – Diamond Light Source (Diamond) – as a result of the GCRF START grant. Often from previously disadvantaged backgrounds and female, these students have attended START funded workshops, have collected data remotely, and are being trained by scientists from the Diamond beamlines. They would love to one day visit Diamond to see a synchrotron for themselves and want to develop careers in structural biology and biochemistry. 

Our dream is that each university in South Africa and beyond our borders will have new generation structural biology, synchrotron and drug discovery techniques taking place as a matter of course. In South Africa, our vision is to include lesser known universities like Venda, Fort Hare, and Johannesburg ensuring that those previously unable to access to opportunities will be able to do so. Already, in just over two years, the START network has grown in South Africa to encompass a wide range of university groups/hubs covering a broad variety of research disciplines to address challenges across Africa, as well as globally. 

Take viruses like COVID-19, for example, we have every potential to be able to produce the targeted, appropriate vaccines and drugs needed for our unique situations. Instead of researchers from Europe and America coming to us to collect samples to take over to Europe/America to do their studies, we could be on an equal footing and able to do every stage of the research right here in Africa so that we are well prepared for outbreaks when they occur. 

In terms of our journey at the PSFRU, the GCRF START grant and Diamond Light Source came at the right time for our group, and for me personally. When I got involved with START in 2018, most of my protein crystal structures were solved in-house using a home-source XRD Wits University commissioned in 2008. However, over the years, the life of the machine started depreciating and we had to look for an alternative light source. Prof. Yasien Sayed, Director of the PSFRU, was contacted by START Co-I, Prof. Trevor Sewell, from the University of Cape Town to champion the University of the Witwatersrand’s Structural Biology collaboration with Diamond as part of the South African broader collaboration with the facility, and because Prof. Sayed and I work in the same research unit, he involved my research in his application. 

The common denominator is science! 

“I know some people say that the priorities in Africa are all about hunger, and that doing scientific research is not a priority but if you look at all the challenges here, the common denominator is science!” – Dr Ikechukwu Anthony Achilonu, Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand 

We can’t do without the science and the latest scientific equipment in terms of tackling Africa’s sustainable development goals. Take hunger and the goal of food security, for example. We need drought resistant crops and pest resistance; we need clean water sources and uncontaminated land; we need disease solutions for the animals and a healthy variety of nutritional and affordable crops; we need people who are sufficiently healthy to grow the food, distribute, manufacture and sell it. Indeed, some of the pathogens I am working on right now, such as Schistosomiasis (Bilharzia), affect a prime source of food security on our continent – cattle. The poultry industry is another example where multiple pathogens kill the poultry which people rely on for food. Therefore, investing in science in Africa is imperative for the health of our continent and the world.   

However, sustainable sources of funding are needed to conduct world class science.  Even in terms of small things like shipping samples, it costs over 3500 Rand (£160.00) each time we ship our protein crystals to and from Diamond. This would be prohibitive for many science groups if it were not for grants like GCRF START. The fact that START grant enables us to do the experiments remotely at Diamond, means we can save money – we don’t have to fly abroad to conduct our experiments and we speak the same language so there are no ‘lost in translation’ issues! 

To demonstrate some of the diverse and world class science research we do at the PSFRU I have outlined three examples below, which benefit from the GCRF START grant. 

Exploring language and cognition: untangling the neuromolecular networks in the brain 

Dr Sylvia Fanucchi’s research looks in detail at a particular node of interaction that is implicated in Autism. This involves investigating the FOXP family of transcription factors which are associated with language and cognition. Her studies aim at untangling the neuromolecular networks in the brain by identifying the nodes of interactions associated with these proteins. In order to do this, Dr Fanucchi explores protein-protein interactions and protein-nucleic acid interactions and how they influence each other in these large neuromolecular complexes. Through the GCRF START grant using the Diamond synchrotron, Dr Fanucchi can investigate the structures of both protein-DNA and protein-protein complexes. This information is highly valuable in dissecting the interactions within these neuromolecular complexes at atomic resolution and is critical to answering the questions posed by Dr Fanucchi in her research. 

New insights into the South African HIV-1 subtype C protease  

Another example of success is Prof. Yasien Sayed’s research on the HIV C protease¹ – the strain of the HIV virus we have in South Africa, whereby Prof Sayed and his team are the first to solve the type C protease at unparalleled resolution. This is a significant success (pending publication) which has been made possible with access synchrotron techniques at Diamond with the GCRF START grant². This paves the way to repurpose AntiRetrovirals (ARV’s) that are tailor-made for the type of HIV we have here in South Africa so that in years to come, HIV prevention and treatment can be far more effective than they are now. Currently, the ARV’s employed here in South Africa are not tailored specifically for our strain of the HIV virus, which means that the side effects are more than they should be (leading to problems with ARV adherence) and drug resistance. 

Schistosomiasis/Bilharzia – solving the 3D structure of the Schistosoma japonicum Glutathione S-transferase (GST ) protein 

“Access to facilities at Diamond has enabled young and emerging researchers, such as Dr. Achilonu in my Unit to realise their potential by publishing their research in internationally peer-reviewed journals.”  –

Prof. Yasien Sayed, Director of the Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand, South Africa 

There are several milestones yet to be reached but my journey with the GCRF START grant is already yielding fruitful outcomes for Africa. My publication³ titled “Molecular basis of inhibition of Schistosoma japonicum glutathione transferase by ellagic acid: insights into biophysical and structural studies” is one of those milestones achieved over the past three years. Using I03 & I04 beamlines at Diamond, we were recently able to solve the 3D structure of the Schistosoma japonicum GST protein at an unprecedented resolution of 1.53 Å- amongst the highest resolution in the current global protein database for this enzyme!  

The resulting publication emphasises the need to exploit the unique structural diversity between Schistosoma GST and other human GSTs for a rational approach to design new generation anthelminthics. Without the high-resolution structure of the Schistosoma GST-in-complex with the potential natural product (Ellagic Acid) – which we aim to study for the design of new anti-Schistosoma drugs – it would have been difficult understanding several empirical observations made in our research. Achieving these results means we can now progress further to find effective drug targets, something only possible to the level we need using synchrotron techniques. I am very grateful to the GCRF START grant and Diamond for this opportunity.  

Our vision to collaborate with groups in other African countries is also progressing. One such group is a medical research institute working on Schistosoma in Kenya with whom we hope to have a collaboration up and running by early next year.  Now that we have new insights afforded by the solved structure of the Schistosoma japonicum GST protein, we need to know that the drug target we are investigating is active against an entire parasite – either as a parasite on its own or in an animal. A collaboration with the Kenyan group offers exciting opportunities to explore this. I also have students from Nigeria, Zimbabwe and Namibia who will be joining us next year; and one from India, therefore our group is truly pushing the boundaries geographically as well as scientifically!  

Towards an African Light Source 

For many, the ultimate vision is having an African Synchrotron Light Source on the African continent. However, it may take years before this is possible and therefore, in the meantime, the START grant enables us to move closer to fulfilling our vision to inspire creative and collaborative scientific research and equip the next generation of scientists in structural biology (and energy materials) to use synchrotron equipment and techniques. I pray and hope that GCRF START and Diamond continue this incredible journey with us, long into the future.  

Read more here about the UN’s Sustainable Development Goals. 

More about Dr Achilonu 

Dr Ikechukwu Anthony Achilonu is Senior Researcher and the Interim South African Research Chair (NRF/SARChI) in Protein Biochemistry and Structural Biology at the Protein Structure-Function Research Unit (PSFRU), School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand in South Africa.  

Publications: https://pubmed.ncbi.nlm.nih.gov/?term=Achilonu+I&cauthor_id=30183110