Category: Profiles

“Abundant energy resources without adequate human resource and access to cutting edge infrastructure remains Africa’s contradiction and greatest challenge to harnessing its primary resources to useful forms. The GCRF START grant has been the vehicle towards the realisation of both, with Dr Francis Otieno being the success story to this initiative. His journey encompasses the germination to shoot culminating with the growth to a potentially giant tree visible in the horizon and useful in the vicinity” – Prof. Daniel Wamwangi, University of the Witwatersrand, South Africa.

It has been said that “The future belongs to those who believe in the beauty of their dreams”[1], but the truth is that so many of our dreams seem at first absolutely impossible. How do you dream of what you cannot visualise? Yet this is the story of a village boy in rural Kenya who knew nothing about experimental research laboratories or STEM, but years later became an international renewable energy researcher with a PhD in the START collaboration, with several papers published[2]. My name is Francis Otieno and I am telling this story to inspire school kids, emerging researchers, and everyone – your dreams are possible!

From village schoolboy to PhD student – the beginnings of my renewable energy dream 

My story begins as I progressed into high school and experienced the heavy environmental pollution from the congested slums of Mathare in Nairobi, Kenya. Large numbers of smoking cars in the streets and continuous electricity blackouts were the norm, especially at the slightest onset of rains. When I look back, this was the start of my dream of making a difference to society and our communities, the start of a long journey in the quest for clean, sustainable renewable energy.

Today I am a GCRF START Postdoctoral Research Fellow (PDRF) in the field of Solar Energy research. I was born in rural part of Kenya called Seme Kadero, in Kisumu County, to a big polygamous family of four mothers and 27 children. I was number 20 in our family and my father, born in 1928, was quite passionate about his kids attending school but none before me made it to university. We were allowed to go to school in the mornings but had essential chores in the afternoons. We grew up grazing cattle barefoot and cultivating land in alternation with school hours – we couldn’t even afford to buy shoes.

My father saved some money for me to attend high school but soon realised this was sufficient only to buy school uniform and other items required for admission but not school fees. I had to make do with a new school uniform, including long trousers and shoes for the first time, which I wore at home while waiting for my father to raise the fees. I didn’t know what to read during those weeks, so after putting on my school uniform each day, I would go to the newspaper vendor, and ask to read all the daily newspapers with him, and then go home in the evening.

My passion was to realise my father’s dreams one day and return home with a title earned from studying. I wanted to be a teacher and contribute immensely to society. My Physics Teacher at Eastleigh High School in Nairobi really believed in me which made a huge difference. He gave me a project using angular inclination and the concept of rectilinear propagation of light to design a device that could be used to measure the height of any building/tree from a distance without having to climb it! This kickstarted my love of science and drove my research career ambition.   

I competed through the district and province and became the second best in the National Science Congress. The fire for research was then fully ignited, fuelled by the fact that I didn’t have a stable light source at night to study, in addition to the effects of environmental pollution. School and learning were vital.  To avoid being mugged for our precious school books, we would walk to and from school 6 km, rising early each morning and singing on the way back home to deter anyone from stealing our text books to sell on for drugs.

My father had long retired from active business relying instead on peasant farming. Our tradition holds that our elder brothers help to cover school fees, which was a challenge as they were equally struggling to settle down in life. With all these hardships, my ambition was to improve performance at school which had back then only a 2-5% pass rate to public university. As a group of high school learners, we managed to turn this around and many secured a place at our public university where we could access government funding.

The best teacher teaches from the heart and not just the textbook, and this is what I intended when I chose a Bachelor of Education degree at Egerton University more than 100 miles northwest of Nairobi. I knew my heartfelt approach meant a lot to my father who has always urged me to do well and surpass any problems on the way. When I got my first Degree in Education teaching physics and mathematics, many of my pupils did well in my subjects. I am a proud teacher having seen them move into good careers using the physics and mathematics they had been taught.

My next thought was that the combination of research and teaching would be more impactful to society, so I enrolled for an MSc in Physics at the University of the Witwatersrand (Wits) in South Africa. Getting accepted on the course wasn’t easy, and I was rejected four times. Finally, in 2014, I joined Wits after resigning from my high school teaching job. This bold step would not have been possible without the encouragement of Prof. Daniel Wamwangi, Associate Professor in the School of Physics at Wits. I am forever grateful for the trust he had in me, the strong motivation he gave, and incredible guidance he has accorded me during my research journey at Wits.

Through his dedicated supervision I was able to successfully earn my MSc, within the time limit, and immediately enrol for a PhD, which I completed within a record time of 30 months together with an output of several publications. During my PhD journey, Prof. Daniel Wamwangi and Prof. Alex Quandt, Professor in Computational Physics in the School of Physics at Wits, formed the best team for supervision. From their immense expertise and with much hard work, I learnt so much within a record time and got exposure to advanced techniques, as well as collaborations within and beyond Africa.

I invited my then 92-year father to my graduation, and tears of joy flowed freely when he landed in Johannesburg for this happy event and throughout his three weeks stay with me in South Africa. It was his first time owning a passport and boarding an aeroplane and seeing his child graduate with the much-desired title of a Doctor of Philosophy. When my father returned to our village in Kenya, he would host sessions of storytelling about these experiences and remembers every tiny detail: his 20^th child brought home his dream!

I told myself that although I was the first in the family to climb to this height of education, I would not be the last. Through this inspiration, four of my younger siblings have now earned their first degrees, and former students, friends and relatives have followed suit in South Africa and Kenya.

GCRF START Postdoctoral Research Fellowship and participation in national and international science outreach events

Through hard work with good output, I was approached by my current host, Prof. Dave Billing in the Department of Chemistry at Wits, and he suggested that I apply for a Postdoc position funded by the GCRF START grant, even before my PhD thesis examination results were back. I was highly convinced that this was the best news ever, and indeed, being accepted by START would help my career and personal growth because I needed exposure outside of Africa as well as within, to move my research forward.

START was a real blessing at the right time when I truly needed it. The GCRF START grant funded my Postdoctoral Fellowship at Wits for two and a half years.  With START, I have been able to obtain lots of data results which have enabled me to publish in reputable journals. Being part of the START network has given me opportunities to collaborate with like-minded researchers at the UK’s University of Oxford, the University of Sheffield and the UK’s world-renowned national synchrotron – Diamond Light Source (Diamond). Through these interactions, I have learnt many new skills and exchanged knowledge and various perspectives.

In addition, back in South Africa and with support from the GCRF START grant to purchase the necessary kits, I participated in several community outreach programmes, including hosting an awareness and outreach activity for the 69th Lindau Nobel Laureate Meeting 2019 on Physics at the University of the Witwatersrand, which I attended in Germany. This was funded by The Academy of Science of South Africa (ASSAf), in partnership with the Department of Science and Technology (DST). The 2019 meeting – known by its Twitter hashtag #LINO19 – was dedicated to physics and was attended by 39 Nobel laureates and 580 young scientists from 89 countries. It was particularly meaningful for our South African contingent because South Africa hosted the International Day of Light that year. I also participated in the University of the Witwatersrand’s Yebo Gogga Exhibition and Focus Day, which assists young learners who need guidance into future careers such as in Physics.

Cleaner, cheaper energy sources through collaborations in cutting-edge advanced materials’ characterisation

Finding alternative cheaper energy sources using locally available materials such as organic polymers is the basis of my research. To provide clean renewable energy sources, the current market is dominated by silicon based solar cells which are high cost arising from the expense of extracting Silicon from its raw materials (sand) and due to their lower efficiency. Thin-film solar cells are known as second generation solar cell fabrication technologies to produce power electrical energy.

I focus on using nanoparticles technology such as plasmonics to realise efficient cheaper sources of energy and to find alternatives to silicon solar cells. My research interests are renewable energies and energy policy, and emerging solar technologies, with my focus under the GCRF START grant on materials’ characterisation, device fabrication and testing of thin films solar cells such as Organic Solar Cells (OSCs), perovskites, and dye sensitized solar cells. My project also explores ways to enhance the performance of these thin film devices through incorporation of nanoparticles technology and spectral conversion thin films with the ultimate goal of realising an efficient, cheaper source of solar energy and device-making for local and global markets

The GCRF START grant facilitated buying my research materials, and made and strengthened Africa-UK collaborations, with lab visits to the UK. This gave me exposure to cutting-edge opportunities and joint proposals to perform advanced materials characterisation such as Grazing Incidence Wide Angle X-ray Scattering (GIWAXs) at Diamond, and access to UK laboratories in the Materials Physics Group at the University of Sheffield with GCRF START Co-I, Professor David Lidzey, and to the Advanced Functional Materials and Devices Group (AFMD) with GCRF START Co-I, Professor Moritz Ried at the University of Oxford.

The newly acquired National Thin-Film Cluster Facility for Advanced Functional Materials based at the University of Oxford is capable of being an epicentre for novel thin film development within the UK and beyond. This facility certainly places UK at the centre of the development of next-generation materials and devices for applications in energy, photonics and electronics. Access to this facility through my on-going collaboration with Oxford will certainly revolutionise my research prospects with increased potential of producing publications in collaboration with the AFMD group, namely Dr Pascal Kaienburg and Irfan Habib.

 In the Materials Physics Group at Sheffield University, Rachel Kilbride and Dr Joel Smith assisted me with carrying out GIWAXs on organic thin films. At Diamond, Dr Thomas Derrien guided me with joint beam time proposals enabling us to do measurements both at Diamond and the European Synchrotron Radiation Facility (ESRF). These collaborations and networks I aim to continue being involved in, and were made possible by Prof. Billing, who has much expertise in powder diffraction and energy materials across research networks within, and beyond Africa. I am always grateful for the faith he had to appoint me as a PDRF, and I have valued his immense support. Also, key is Prof. Wamwangi, who has been a great mentor in my research journey, from experimental techniques to manuscript preparation. As a result, I have contributed to several papers looking at solar cells materials and device-making instrumental to industries, working on improving the performance of solar cell devices highly needed in the global market.

We believe that the future of all technologies is ‘smart’ and for this reason, and Organic Solar Cells (OSCs) research is critical to realise efficient energy sources with advantages over current silicon solar cells, due to the abundance of materials and ability for scalable production processes that OSCs offer. Our aim is to contribute to the Sustainable Development Goals 7 (energy) and 3 (Climate) and the growing global demand for innovative, world class solar energy. Also, our research findings form the basis for teaching solar cell technology to undergraduate and postgraduate students as well as other Research Fellows back home.

Inspiring hope, enabling others to dream – bringing my expertise back home

Although the journey is a long one, I am excited to have embarked on making a difference in the society through our research; and I am proud that my dream of impacting young people from rural areas like my own was realised when I became a teacher. To continue investing in developing others, I have started mentoring undergraduate and postgraduate students at the University of the Witwatersrand and now at Maseno University, Kenya, where I have been offered a job as a lecturer.

The GCRF START grant exposed me to new skills and advanced equipment, and through my successes and links to START, I was able receive the British Council Newton Travel Grant which will enable me to visit Oxford for a period of six weeks, currently planned for September 2021. This exposure together with much sought after skills and strong collaborations will be very useful to me as a young researcher looking forward to supervising postgraduate students back in Kenya, upon the completion of my Postdoctoral Fellowship.

As Kenyan bush-pilot, Beryl Markham[3], once said, “Africa is mystic; it is wild; it is a sweltering inferno; it is a photographer’s paradise, a hunter’s Valhalla, an escapist’s Utopia. It is what you will, and it withstands all interpretations.”  – one aspect of interpretation is that here, in my story and the story of START, hope does not disappoint!

Read more about the UN’s Sustainable Development Goals here

[1] quote by Eleanor Roosevelt

[2] https://start-project.org/home/research/publications/ and https://scholar.google.com/citations?user=M9Ysk-4AAAAJ&hl=en accessed 20.7.2021

[3] https://www.historynet.com/remarkable-mrs-markham.htm accessed 20.7.2021

“It is fascinating! I believe the GCRF START grant has laid a strong foundation for me to becoming an independent early career Structural Biologist. Now I am hands-on, a biochemist being chaperoned into the world of X-rays, electrons, neutrons, quantum mechanics and GPUs[1]”

Dr Stanley Makumire, GCRF START Postdoctoral Research Fellow, University of Cape Town, South Africa.

My name is Stanley Makumire. I was born in Zimbabwe and have had a passion for Maths and Science for as long as I can remember. My desire is to gain an understanding of how disease works at the atomic level and thereby address important Sustainable Development Goals for health and wellbeing (SDG3). I had not encountered structural biology until I attended the Biophysics and Structural Biology at Synchrotrons workshop in Cape Town in early 2019 (17‐24 January), which was jointly funded by the GCRF START grant and the International Union of Pure and Applied Biophysics. At that meeting, I saw the cutting-edge work being done by people in the GCRF START programme and realised that understanding macromolecular structure was the key to understanding biochemistry, and this has inspired my research journey ever since. At the time I was completing my PhD at the University of Venda in the Limpopo province of South Africa, where none of the resources to do such work were available. Therefore, I was determined to collaborate with the GCRF START programme at the University of Cape Town (UCT).

Given the disease burden in Africa, my main career goal is to eliminate or minimise disease progression using molecular and structural biology tools, with proteins as targets using small molecules designed by rational processes as drugs. This knowledge has provided insights used to design medicines and vaccines. I am motivated by the rapid advance of biophysics that we have witnessed in response to the COVID-19 pandemic. This has clearly demonstrated the power of today’s visualisation technology and the field of Structural Biology in vaccine design.

Studying the mechanisms of enzymes of the nitrilase superfamily

I was motivated to join Prof. Bryan Trevor Sewell for my Postdoctoral Fellowship, which I was awarded through the GCRF START grant in 2020. Prof. Sewell is a GCRF START Co-investigator in the Structural Biology Research Unit at the University of Cape Town.  I had applied to do postdoctoral studies on the mechanisms of enzymes of the nitrilase superfamily. These ubiquitous enzymes play a variety of roles in cellular processes, and many have found industrial roles in chemical synthesis and environmental protection. However, discovering how they work has been beset with difficulties.

It has been known for some time that three different amino acids play a pivotal role in their function: a cysteine, two glutamates and a lysine. Excellent clues have come from X-ray crystallographic studies (Fig.1), but the literature contains a multitude of different interpretations of the available evidence. The problem is that X-rays cause the cysteine to become oxidized and cannot image hydrogens (which are a key players) and electrons destroy the glutamates so that they are invisible in images obtained by electron microscopy. The tricks to circumvent these problems used by various investigators have introduced artifacts of their own and therefore a definitive mechanism has eluded humanity.

Overcoming the challenges with neutrons

Neutrons are known to be the least damaging of all atomic resolution imaging probes and furthermore, they enable the imaging of hydrogens (in fact, deuterium that has exchanged with the natural hydrogen). But imaging by neutron crystallography is also beset by difficulties, including the fact that the crystals required must be enormous making it necessary to prepare vast quantities of protein. To add to these difficulties, there are only six suitable neutron beams in the world, so access to an appropriate facility is very restricted. I have overcome these difficulties with the help of Zoë Fisher, who is the group Leader of the Deuteration and Macromolecular Crystallization (DEMAX) platform at the European Spallation Source, and Mathew Blakeley, instrument scientist at the Quasi-Laue diffractometer (LADI-III) at the Institut Laue-Langevin (ILL). I am in the process of collecting data and learning of the remarkable insights that can be obtained by using neutrons to study the enzyme mechanism. Determining a neutron structure of this amidase will form the basis of proposing a novel mechanism and I am excited since the preliminary results are very promising. This would be a game changer!

Opportunities, resources, and capacity building through the GCRF START grant

“GCRF START has provided me with opportunities and resources that I would never have believed were possible to access from the African continent. Participating in the START grant programme has been an extraordinary experience.”

During the first year of my GCRF START-funded Fellowship, I was able to collect, process and interpret X-ray data, process and interpret high resolution cryoEM data collected at the world-class Electron Bio-Imaging Centre  (eBIC) at the UK’s national synchotron, Diamond Light Source, thereby solving the structure of the Plasmodium falciparum glutamine synthetase (deposited as EMDB entry ID EMD-12589). I used molecular mechanics software to explore the active site of amidases and interpret quantum mechanical models of the amidase active site, thus adding substantial value to the X-ray structures. I have participated in projects related to anti-malarial drug design and had the opportunity to reinterpret the literature on amidase mechanism.

I have met and interacted with leading scientists through my GCRF START Fellowship who have helped me to achieve my objectives. I have also met other early career scientists involved in START projects and collaborations, and I am amazed at how far they have progressed. I am excited that, because of the GCRF START grant, I am becoming one of the very small cohort of young people in Africa that have the knowledge to contribute to the field of Structural Biology.

Commenting on Stanley’s research progress and his involvement in multiple international collaborations, Prof. Sewell said,

“Stanley has maintained spectacular productivity in spite of the challenges caused by lockdown due to the Covid-19 pandemic. He has engaged with a remarkable array of science and technology at UCT’s Aaron Klug Centre for Imaging and Analysis and has built rapidly on the work of others to bring several projects to fruition. His enthusiasm and passion have been maintained by interaction with the GCRF START team and he has leveraged this network to make contact and collaborate with neutron crystallographers at ILL and DEMAX. This clearly demonstrates the process by which capacity has been built in Africa through the GCRF START grant.”

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

[1] Graphics Processing Units

My name is Maria Hamunyela, and I am a second year PhD student in the structural biology research group at the University of Pretoria, South Africa. Born and raised in a small town in northern Namibia, I was inspired to pursue my studies in science by women scientists that I have come across. Women in science face extra challenges, having to balance their careers and personal lives. I was raised by strong black women, including my mother, from whom I draw my strength. My parents never had the same opportunities and therefore, on completion of my studies, I will be the first PhD holder in my family.

Although I work for the University of Namibia as a technologist, I chose to continue my studies at the University of Pretoria under the supervision of GCRF START Co-I, Prof Wolf-Dieter Schubert, due to limited research funding and the lack of structural biology facilities in my country. This has provided me with access to world-class equipment, such as the UK’s national synchrotron, Diamond Light Source (Diamond).

The impact of Escherichia coli (ETEC) and related diseases – the scale of the challenge

I am currently investigating the secreted EatA protein of enterotoxigenic Escherichia coli (ETEC) bacteria. ETEC commonly causes watery diarrhoea in children younger than five years old killing many children in this age group. ETEC also causes malnutrition and stunting in children. I decided to work on this project because ETEC affects young children in developing countries in regions with limited access to clean water and sanitation. This is true of many people in both Namibia and South Africa who are correspondingly severely affected by water and food borne pathogens such as ETEC and Shigella.

Globally, ETEC and Shigella are estimated by the World Health Organisation to cause ~400 million episodes of diarrhoea annually in children under five years of age (WHO 2009) causing moderate and severe stunting in ~2.6 and ~2 million children, respectively[1]. Studying ETEC can help to develop vaccines and drugs against ETEC and related diseases.

Studying the functions and structure of the EatA protein passenger domain

The passenger domain of the EatA protein is required for the virulence of ETEC. It degrades Mucin 2, a protective protein secreted by, and covering the intestinal epithelium. Previous reports show that the EatA passenger domain is a potential vaccine candidate for ETEC and other enteric pathogens such as Shigella flexneri. However, the functional and structural properties of the EatA passenger domain have not been extensively studied. The full biological function of EatA passenger domain is therefore not well understood and might support infections in yet other ways. Studying the functions and the structure of EatA passenger domain will provide a better understanding of ETEC pathogenesis.

A first step in studying the EatA passenger domain will be to introduce an affinity tag in the middle of the protein to simplify protein production and purification. This is non-trivial as both the N- and C-terminal ends are not available for the placement of such a tag and inserting it in the wrong place could affect the stability and the function of the protein. Once the protein has been produced and purified, the substrate specificity will be investigated by designing an enzyme activity assay. Observations on the optimal substrate will ideally allow the development of an inhibitor. Identifying other host proteins that interact with the target protein could provide information about additional functions. Structural and biophysical experiments will include thermal unfolding and refolding studies, co-crystallisation and finally X-ray diffraction to provide a fuller understanding of the role of EatA.

The WHO/UNICEF Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) aims to reduce deaths from diarrhoea in children younger than five to less than 1 per 1000 live births by 2025 (WHO/UNICEF, 2013)[2]. Hopefully designing an inhibitor for EatA will be a fundamental step in achieving this goal

Collaborating with the GCRF START grant and next steps

It took more than a year of searching for opportunities before I came across Prof Wolf-Dieter Schubert and he accepted me to join his structural biology research group at the University of Pretoria. This is how the GCRF START programme afforded me the opportunity to study towards my PhD studies. The main benefit is that I now have access to Diamond, to world-class synchrotron techniques, and I have the reagents that I need to do my research. I am also getting scientific training, not only in the laboratory but through workshops connected to START. In addition, I am fortunate to be a part of a supportive research group.

As I am employed by the University of Namibia as a technologist, I will return to Windhoek (Namibia) in the future, and hopefully start my own academic research group in structural biology. If interesting opportunities arise, I would love to work for an international research facility or even the public sector. While the scientific industry in Namibia is still in its infancy, I may be able to bring my own knowledge to setting up a new company.

Read more about the UN’s Sustainable Development Goals here

[1]https://www.who.int/immunization/research/meetings_workshops/6.Enterotoxigeni_Escherichia_coli_ETEC_A.Louis_Bourgeois_PDVAC_2016.pdf?ua=1 accessed 16.03.2021

[2] https://www.who.int/publications/i/item/the-integrated-global-action-plan-for-prevention-and-control-of-pneumonia-and-diarrhoea-(gappd) accessed 16.3.2021         

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

My love for science and medicine

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

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

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

Re-training as a protein crystallographer

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

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

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

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

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

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

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

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.

“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