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

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

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

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

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

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

Passing on the love of learning to other young scientists 

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

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

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

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

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

Investing in African Early Career networks through GCRF START grant 

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

 Prof. Dirk Opperman, University of the Free State 

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

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

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

Exposure to international research collaborations and facilities  

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

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

Gaining the competitive edge! 

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

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

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

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

Acknowledgements 

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

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

Tolmie C, Do Aido Machado R, Ferroni FM, Smit MS and DJ Opperman (2020). Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation. Catalysts 10(3): 339. doi: 10.3390/catal10030339 (Impact factor 3.444): https://www.mdpi.com/2073-4344/10/3/339 

Carmien’s profile on Research Gate Profile

What GCRF START means for my research on human papillomavirus (HPV) 16 pseudovirions

“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.  

Melissa Marx from the University of Cape Town, South Africa. Photo Credit: Rebekka Stredwick.  ©Diamond Light Source 

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). 

Melissa Marx at the University of Cape Town, South Africa, preparing grids used to mount samples before shipping to the UK’s national synchrotron, Diamond Light Source. Photo credit: Rebekka Stredwick. ©Diamond Light Source 

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. 

Melissa Marx next to the at M06 Titan Krios electron microscope at eBIC at the UK’s national synchrotron, Diamond Light Source. ©Diamond Light Source 

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!  

Melissa Marx (R) with Dr Lizelle Lubbe (L) and Dr Andani Mulelu in the Electron Microscopy Unit at the University of Cape Town. South Africa.
Photo Credit: Rebekka Stredwick. ©Diamond Light Source  

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. 

(From L-R) Dr Priscilla Masamba, Dr Jeremy Woodward, Melissa Marx, Dr Andani Mulelu, Dr Philip Venter, and Prof. Trevor Sewell in the Electron Microscopy Unit at the University of Cape Town’s Aaron Klug Centre for Imaging and Analysis, South Africa. Photo credit: Rebekka Stredwick. ©Diamond Light Source 

References  

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

1. Trottier, H. and E.L. Franco, The epidemiology of genital human papillomavirus infection. Vaccine, 2006. 24 Suppl 1: p. S1-15.  

2. de Villiers, E.M., et al., Classification of papillomaviruses. Virology, 2004. 324(1): p. 17-27.  

3. Chikandiwa, A., et al., Patterns and trends of HPV-related cancers other than cervix in South Africa from 1994-2013. Cancer Epidemiol, 2019. 58: p. 121-129.  

4. Munoz, N., et al., Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med, 2003. 348(6): p. 518-27.  

5. Walboomers, J.M., et al., Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 1999. 189(1): p. 12-9.  

6. Bruni, L., et al., Global estimates of human papillomavirus vaccination coverage by region and income level: a pooled analysis. Lancet Glob Health, 2016. 4(7): p. e453-63.  

7. Draper, E., et al., A randomized, observer-blinded immunogenicity trial of Cervarix((R)) and Gardasil((R)) Human Papillomavirus vaccines in 12-15 year old girls. PLoS One, 2013. 8(5): p. e61825.  

8. Hildesheim, A., et al., Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment. Am J Obstet  

9. Schiller, J.T., et al., An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Vaccine, 2008. 26 Suppl 10: p. K53-61.  

10 Biryukov, J. and C. Meyers, Papillomavirus Infectious Pathways: A Comparison of Systems. Viruses, 2015. 7(8): p. 4303-25  

11. Phasa.org. Implementation of HPV vaccination in South Africa. 2015; Available from: https://phasa.org.za/2015/02/26/implementation-hpv-vaccination-south-africa/.  

12. Schafer, G., et al., Vimentin Modulates Infectious Internalization of Human Papillomavirus 16 Pseudovirions. J Virol, 2017. 91(16). 

Cultivating ACE research skills to tackle cardiovascular disease

“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 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.  

Dr Lizelle Lubbe, GCRF START Postdoctoral Research Fellow. Photo Credit: Rebekka Stredwick. ©Diamond Light Source 

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. 

From left: GCRF START collaborating scientists, Dr Priscilla Masamba, Dr Jeremy Woodward, Melissa Marx, Dr Andani Mulelu, Dr Philip Venter, Dr Lizelle Lubbe, Prof. Trevor Sewell at the University of Cape Town. Photo Credit: Rebekka Stredwick. ©Diamond Light Source 

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. 

GCRF START Postdoctoral Research Fellow, Dr Lizelle Lubbe from the University of Cape Town (UCT) with START collaborator Dr Andani Mulelu at the University of Cape Town’s Postgraduate Showcase outreach event in July 2019. Dr Mulelu is a researcher at UCT’s Drug Discovery and Development Centre (H3D). 
Photo credit: Dr Jeremy Woodward. ©Diamond Light Source 

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. 

Dr Lizelle Lubbe transferring a puck containing the cryo-EM grids of ACE from the shipping dewar to be clipped for data collection session at eBIC at the UK’s national Diamond Light Source synchrotron. Photo credit: Dr Jeremy D Woodward. ©Diamond Light Source 
GCRF START Postdoctoral Research Fellow,Dr Lizelle Lubbe, with START collaborator, Melissa Marx from the University of Cape Town (UCT) next to the Titan Krios III (M06) at eBIC embedded at the UK’s national Diamond Light Source synchrotron, which was used to image ACE. Melissa is an MSc student co-supervised by Dr Woodward at UCT. 
Photo credit: Dr Jeremy Woodward. ©Diamond Light Source 

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.  

GCRF START Co-Investigator, Prof. Ed Sturrock, and GCRF START Postdoctoral Fellow, Dr Lizelle Lubbe, at the GCRF START launch in Oxford, UK. 
Photo credit: Prof. Ed Sturrock. ©Diamond Light Source 

Studying ACE for the future design of ACE inhibitors 

ACE is a dumbbell-shaped protein comprised of two domains (the N- and C-domain) which perform diverse physiological functions: the C-domain is mainly responsible for blood pressure regulation while the N-domain is important for regulating scar tissue formation. The main focus of Prof. Sturrock’s research is to design inhibitors that selectively bind to the N- or C-domain. Selectivity is very important since the side-effects associated with current ACE inhibitors are due to equal inhibition of both domains.  At the end of my BSc (Med)(Hons) year, Prof. Sturrock (in collaboration with Prof. Kelly Chibale at UCT) discovered a molecule (33RE) which binds with 1000-times greater affinity to the N-domain than the C-domain of ACE5. N-selective ACE inhibitors are antifibrotic and as such, show potential for the treatment of fibrosis (excessive scar tissue formation).  X-ray crystallography was used to study the binding of 33RE to the N-domain but the reason for its selectivity remained a mystery.  One limitation of this technique is that it only gives you a static ‘snapshot’ of the protein’s structure while proteins are naturally very dynamic when in solution (as in the body).   

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

GCRF START ensures the continuation of postdoctoral research 

As a GCRF START postdoc, I am continuing this research in collaboration with Prof. K Ravi Acharya7 at the University of Bath and we have recently discovered that these differences in dynamics also affect the binding and selectivity of ACE inhibitors from different classes8 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

Fulfilling the vision! Why GCRF START means everything to me

“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.  

Dr Ikechukwu Anthony Achilonu, Protein Structure-Function Research Unit (PSFRU), School of Molecular and Cell Biology,
Faculty of Science, University of the Witwatersrand. ©Diamond Light Source 

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. 

Dr Ikechukwu Anthony Achilonu (L), Prof. Yasien Sayed (R), and Dr Sylvia Fanucchi (Front) from the Protein Structure-Function Research Unit (PSFRU),
University of the Witwatersrand. ©Diamond Light Source 

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 

How I became an HIV research scientist – One Zimbabwean’s story

“Being a young woman in science, forging my career, can be challenging at times. However, I want to be an inspiration for young African girls and women to know that it is possible to fulfill your dreams and passions.” – Dr Thandeka Moyo, GCRF START Postdoctoral Research Fellow at the South African National Institute for Communicable Diseases and affiliated to the University of the Witwatersrand, South Africa.

Witnessing the HIV pandemic

My name is Thandeka Moyo. As a young woman growing up in Zimbabwe, my eyes have been privy to the evolution of HIV/AIDS in our country and region over the past three decades. I have not only witnessed the viral evolution (the way HIV is always changing and mutating), but also people’s perceptions toward this viral infection.  Before I reached my teenage years in the 1990’s, I already knew there was a “terrible disease” that could not be named, and which was claiming the lives of people around me. When someone died and nobody freely offered the cause, everyone knew not to ask.

In the 2000’s, things began to change. Antiretroviral therapy was more widely available, and more and more HIV-positive people were living healthy lives. But still, the stigma continued. This raised my curiosity. What is this disease, what causes it, and why is there a stigma around it?

Dr Thandeka Moyo, GCRF START Postdoctoral Research Fellow. Photo credit: Thandeka Moyo. ©Diamond Light Source

A growing passion – becoming an infectious diseases and HIV research scientist

From the age of 15 years old, I knew I wanted to learn about infectious diseases, what caused them and how we could eradicate them. I had no idea how I was going to achieve this goal of mine except through single-mindedly studying science-related subjects and hoping for the best!

I studied my way through the sciences in high school and successfully applied to Rhodes University in South Africa for an undergraduate degree.  In my fourth year (Honours) I undertook a malaria-related project under the supervision of Prof. Heinrich Hoppe. This was it! This was the first year I felt I was contributing to scientific research, which not only affirmed my love for studying infectious diseases but also my desire to go further and study HIV.

This led me to the University of Cape Town where I obtained both an MSc and PhD in the laboratory of Dr Jeffrey Dorfman researching within an HIV vaccine-related field. Here, I finally got to work on virus I had wished to work on all these years!

One of the biggest problems with HIV is its diversity. We concentrated on broadly neutralising antibodies towards HIV – antibodies which prevent various global strains of the virus from entering human cells and establishing infection. Broadly neutralising antibodies may be the key to an effective HIV vaccine and therefore my research focuses on studying the interactions between these antibodies and the HIV Envelope – which forms the outer coat of the virus. Knowing exactly where and how these antibodies bind to diverse strains of HIV may aid in the design of vaccine components which can trigger these antibody responses upon immunisation.

During my PhD, I had the opportunity to conduct a research visit to the Hospital for Sick Children in Toronto, Canada, in the laboratory of Prof. Jean-Philippe Julien. I went there to conduct a portion of my research, and that is where my love for structural biology began.

Mentors and synchrotrons – collaboration through GCRF START

“Thandeka is a wonderful example of an emerging African female scientist. She is single-minded, strives to identify important scientific questions, and is generous with her ideas. She is a natural leader who is already, at this early stage in her career, carefully building capacity in structural biology.”

Professor Penny Moore, National Institute for Communicable Diseases, South Africa

For my postdoctoral studies, I have continued in HIV research but with a sole focus on protein biochemistry and structural biology in the laboratory of Prof. Lynn Morris and Prof. Penny Moore at the National Institute for Communicable Diseases (NICD) in Johannesburg. It is here that I first heard about GCRF START.

As a GCRF START Postdoctoral Research Fellow, START has given me opportunities I could have never imagined. I now have access to a world-class synchrotron, the UK’s national synchrotron – Diamond Light Source, where I can send my HIV-antibody complexes to obtain the vital diffraction data I need for my research – to date I have used beamlines i04, i04-1 and i03. I was given the opportunity to present at the START launch event in Oxford (UK) in March 2019, and subsequently at various START meetings, Institutes and Centres, such as CAPRISA, with whom I collaborate.

One of the greatest benefits of START, however, has been the fruitful collaborations and relationships I have built with South African structural biologists who have significantly aided my career progression, and I extend special thanks to GCRF START Co-Investigators, Prof. Trevor Sewell, Prof. Dirk Oppermann and Prof. Wolf-Dieter Schubert. In addition, Diamond staff have been exceptionally helpful answering my questions and providing me with assistance during beamtime.

Dr Thandeka Moyo, GCRF START Postdoctoral Research Fellow. Photo credit: Thandeka Moyo. ©Diamond Light Source

Mentoring and inspiring young women in science

“Dr Moyo is a great mentor; she provides practical guidance that has been motivating and beneficial to my professional development. She is inspirational, driven and talented; it is a privilege to be mentored by her” – Zanele Makhado, Medical Scientist at the National Institute for Communicable Diseases, South Africa.

I have been fortunate to have found extremely supportive mentors in Prof. Penny Moore and Prof. Lynn Morris at the NICD, who have encouraged my independence and supported me throughout my Postdoctoral studies. Finding mentors and supervisors who are aligned with one’s vision is one of the most important decisions to make in this scientific journey!

The aspect of science I enjoy the most is encouraging the next generation of young women to pursue a career in academia and other science-related industries. I have been involved in school outreach initiatives from my university days which has continued throughout my postdoctoral studies with involvement in student ‘shadowing’ and through presentations to school children. Due to the Covid-19 lockdown, we recently undertook outreach to school children remotely via Zoom.

I am currently a mentor to one MSc student and two medical scientists here at the NICD. All three are intelligent women with bright futures in science. It has been a pleasure working with them towards their scientific goals. Mentoring has taught me a great deal about how to support other emerging scientists and has helped me learn to effectively juggle between working on my own project, while being present to ensure I assist them with theirs.

An end to the pandemic – forging ahead with my goal

I continue to hope and advocate for the stigma associated with HIV/AIDS to be eradicated, even before the virus itself is eliminated! Those infected with HIV can live long, healthy lives on treatment and with consistent use, ensuring that with undetectable viral loads they will no longer transmit the virus to others. An HIV vaccine may be the most effective tool to completely eradicate the virus and therefore I continue to work in this field with the aim of contributing towards this important goal.

Dr Thandeka Moyo, GCRF START Postdoctoral Research Fellow. Photo Credit: Thandeka Moyo.©Diamond Light Source

“With more people like Thandeka and more programs like GCRF START, Science in Africa can only go from strength to strength!”  –

Professor Penny Moore, National Institute for Communicable Diseases, South Africa

Related articles and websites

https://www.researchgate.net/profile/Thandeka_Moyo

Ending AIDS by 2030 is an integral part of the Sustainable Development Goals (SDGs).

Click here to learn more about the science behind HIV/AIDS.

“The bigger the challenge, the bigger the opportunity for growth.” – Mohamed Abdelaal’s story

“Working on renewable energy development is not just a job for us scientists; we are assisting both people and the environment to meet important Sustainable Development Goals in Africa, and globally.”

Mohamed Abdelaal, Ain Shams University, Cairo, Egypt

In 2018, I joined the GCRF START Program with the support of my supervisor, START Co-Investigator, Prof. Ghada Bassioni. This was the beginning of an exciting new research challenge for me, investigating solar energy by examining the micro-structure of Organic Solar Cells (OSC’s) to monitor how the performance of the cells is affected by their micro-structure under different environmental conditions.  I have faced and overcome many challenges on my path to becoming a solar energy researcher.  My story below explains what has motivated me and how I am benefitting from collaborating with people from the GCRF START grant.

Learning challenges and opportunities in Egypt

I was born in Cairo, Egypt where I have lived most of my life and I love traveling, meeting new people and exploring new cultures, especially when the travel is combined with science and research! During my educational and subsequent research journey, I have faced a lot of different challenges but as someone once said, “The bigger the challenge, the bigger the opportunity for growth” (anon).

GCRF START collaborator, Mohamed Abdelaal, in Egypt. Photo Credit: Mohamed Abdelaal. ©Diamond Light Source

Starting with my secondary school education and my first educational challenge! In 2011, during the Revolution in Egypt, all the education in the country was on hold because of the sudden political circumstances, except for those like me, who were enrolled in international education. I was enrolled in British Secondary education (IGCSE) but due to the situation in Egypt, I had to study the complete syllabus alone at home to ensure I was prepared for the exams, which I was not even sure would take place! Unfortunately, online educational platforms and facilities were not possible at that time but despite these obstacles, I passed secondary school with excellent grades and joined the Faculty of Engineering at Ain Shams University, Egypt, to study for my Bachelor’s degree.

My Bachelor’s degree was in Materials Science and Engineering – a double degree program between Ain Shams University in Egypt and the Technical University of Clausthal in Germany. This meant that in addition to the engineering study and research I had to do, I needed to learn German to undertake study and research in Germany. This also meant I had to manage my time wisely to make sure that both the Engineering study and the German language would be completed in time and with high scores – another challenge!  

A further challenge in Germany, was to study the technical subjects in the German language, yet the only technical expressions I knew were in English! In addition, I had to finish my Bachelor studies early to ensure I didn’t miss the submission date for my Military Service once back in Egypt. Unfortunately, due to delays in receiving my Bachelor certificate, I missed the Military Service submission deadline and had to wait for 6 months. Accordingly, I traveled back to Germany and I found work with Mercedes until the next submission date but at least I had an opportunity to learn some new skills at Mercedes.

Mohamed Abdelaal graduating from his Bachelor’s degree at Ain Shams University, Cairo, Egypt. Photo Credit: Mohamed Abdelaal. © Diamond Light Source

I didn’t want to spend my military service away from the research I ultimately wanted to do, so I decided to do to my Military Service and my Master’s degree at the same time, studying Materials Science and Engineering at Ain Shams University’s Department for Mechanical Design and Production. New challenges awaited as I had to spend a lot of time traveling between the different cities to attend the exams, because my military Service was not in Cairo, where the University is located. I had to repeat some exams which I missed due to Military Service, but I finished all the exams in the end with excellent grades!

Motivated by exciting new research challenges! Organic Solar Cells

Solar cells (also called Photovoltaics or PV) are electronic devices that convert sunlight directly into electricity. Today, PV is one of the fastest-growing renewable energy technologies, and is ready to play a big role in the future global electricity generation mix by providing electricity on a commercial scale and/or arranged in smaller configurations for mini-grids or personal use (IRENA 2020). Non-renewable energy is not yet widely available but by conducting this type of research, I hope one day that this will change. Scientists like myself are working on improving OSC’s because of their high potential to offer cheaper and more flexible energy options[1]. I am motivated by the fact that one day, everyone will benefit from this kind of research, either directly by producing more efficient OSC’s to replace both silicon solar cells and non-renewable energy sources, or indirectly by reducing environmental pollution. If the efficiency of Organic Solar Cells is improved, then countries like Egypt might invest more money and implement additional Solar farms such as the Benban project in Aswan and other solar energy projects.

Building new research networks and using specialised equipment through GCRF START

My research takes place in the Department of Design and Production (Mechanical Division), at the Faculty of Engineering at Ain Shams University; the other part of my research I do in collaboration with START Co-Investigator, Prof. Moritz Riede’s and the AFMD group in the Department of Physics at the University of Oxford in the United Kingdom (UK). GCRF START has introduced me to new research networks and research equipment and made it possible for me to conduct some of my experiments on Solar Cells at the UK’s National synchrotron Diamond Light Source.

GCRF START collaborator, Mohamed Abdelaal, outside the UK’s national Diamond Light Source synchrotron. Photo credit: Mohamed Abdelaal. © Diamond Light Source

In September 2018, I traveled to South Africa on behalf of Prof. Ghada Bassioni to attend a conference funded by GCRF START in Johannesburg. This was a kick-off meeting to help the different groups in Africa get to know each other. Each group presented their research points, progress and future work and I had the pleasure of meeting Prof. Moritz Riede in person and he guided me on my research planning for the coming months. In addition to the technical information we learned during the conference, I met new people from different universities around the world!

GCRF START enabled me to travel to attend the first main START meeting in the UK which took place in March 2019.  At the meeting, with the support of Prof. Ghada Bassioni, I had the opportunity to present about Energy Resources and Challenges in Egypt on her behalf. Then, in January this year (2020) and with the assistance of the GCRF START grant and Prof. Ghada Bassioni’s and Prof. Moritz Riede’s support, I traveled again to the UK but for a longer period this time, and joined Prof. Riede’s group to conduct experiments at both the University of Oxford Vacuum Evaporator (ECHO1) facility, and on Diamond’s the high resolution Beamline I07.

GCRF START collaborator, Mohamed Abdelaal, inside the beamline I07 experimental cabin at the UK’s national Diamond Light Source synchrotron.
Photo credit: Mohamed Abdelaal. ©Diamond Light Source
Professor Moritz Riede and Professor Ghada Bassioni. Photo credit:  Ghada Bassioni. ©Diamond Light Source

However, opportunities always come with challenges and although the plan was to stay until the middle of April, unfortunately, due to the COVID-19 situation, I had to cut short my visit and travel back to Egypt one month earlier. Now I am facing the next challenge of continuing my research during COVID-19 lockdown! But as I said before, “The bigger the challenge, the bigger the opportunity for growth!”

Without START, I wouldn’t have been able to experience these meetings and conferences, and I have learned something new from each of them. To summarise what the GCRF START grant means to me, I would describe it as great exposure and the opportunity to meet new scientists from all over the world, assisting us in building our scientific network. It means facilitating the engagement with audiences through opportunities to give speeches and present our work. Financial support helps us conduct our experiments, access equipment and travel to attend conferences and meetings.

Mohamed Abdelaal presenting on renewable energy resources in Egypt at the first GCRF START meeting at the University of Oxford in the UK, in March 2019.
©Diamond Light Source

Commenting on the collaboration with Mohamed Abdelaal, Prof. Moritz Riede from the University of Oxford, said:

“It’s been great having Mohamed as part of our team in Oxford. Such exchanges are essential if we want to solve global challenges like climate change. Among other benefits, they foster collaboration, create lasting networks and enrich the perspectives of everyone involved. It’s unfortunate that Mohamed’s visit was cut short due to the Covid-19 pandemic, but we got off to a really good start and we continue remotely. We still hope that Mohamed will be able to visit us again soon, and similarly that we’ll be able to visit his group in Egypt, as these exchanges work best if they go both ways. We are in the fortunate position to be part of the GCRF-START project, which supports such collaborations between the UK and partners on the African continent.” 

Related articles

Read more here about Mohamed’s research

Learn more about Solar energy here and the differences between Organic and Inorganic Solar Cells here

Read more here about the UN Sustainable Development Goal 7 for Energy

Footnote:

[1]Organic Solar Cell Materials toward Commercialization; Rongming Xue, Jingwen Zhang, Yaowen Li,* and Yongfang Li; DOI: 10.1002/smll.201801793

Inspiring the next generation of African scientists – Sikhumbuzo Masina’s story

 “From an African perspective, I believe it is vital to inspire young, up and coming scientists. If there is inspiration and collaboration, there is learning, and learning can be passed on. There has to be continuity if science and innovation is to flourish across our continent.”

Sikhumbuzo Masina, University of the Witwatersrand, South Africa

Sikhumbuzo Masina is a PhD student at the University of the Witwatersrand, South Africa, investigating Solid Oxide Fuel Cell (SOFC) electrolytes for alternative energy solutions in Africa and beyond. From humble beginnings as a shepherd in Swaziland, to a PhD student collaborating with the START community, Sikhumbuzo has reached the position he is in today through talent, persistence, and the inspiration of others.

Sikhumbuzo Masina from the University of the Witwatersrand.
Photo credit Rebekka Stredwick. ©Diamond Light Source

One of a group of Master’s, PhD students and post-docs who attended START’s Energy Materials workshop at the University of Cape Town (UCT) in December (2019), Sikhumbuzo is part of START’s ‘extended-family’ through his PhD supervisor and mentor, Professor Dave Billing.

For Sikhumbuzo, possibility is the seedbed for ingenuity and it is this, he explains, which drives his desire to reach out and inspire the next generation of science students. This is Sikhumbuzo Masina’s story in his own words.

Students and post docs at GCRF START’s Energy Materials Workshop (15-17 Dec 2019) at the University of Cape Town. From left to right: Dr Wilson Mgodi, Mathias Kiefer, Sikhumbuzo Masina, Adam Schnier, Chris Mullins.
Photo Credit: Rebekka Stredwick. ©Diamond Light Source

Humble beginnings

I grew up with very few resources and life in Swaziland was very hard. My father passed away before I was born, and my mother couldn’t fund my schooling. From the age of 12 years, I therefore had to work away from home as a shepherd to raise funds for school fees.

I was fortunate enough to work for kind people who took me into their family and encouraged me to go to school. From the money I earned in my spare time herding farm animals and assisting on the farm, I was able to fund my schooling until high school. 

School became too expensive, however, so the Priest at the local Catholic Church took responsibility and paid much of my school fees through a church fund to support youth; the rest was topped up by a government bursary. I am very grateful for this support.

Inspired to think big – my PhD dream!

I did very well in high school and found inspiration through my two ‘brothers’ in the family I was working for who had been to university. They were the people I looked up to and motivated me to work hard and have a vision for my future.

I would say to myself, “They wanted PhDs and I want to have a PhD too at some point in my life”. I did not even know what a PhD was! However, the fact that I saw and liked what they were doing was very important for me.

After I completed school, I took advantage of the Government’s study loan scheme for students because I couldn’t support myself. This paid for my tuition and accommodation and meant I could do my first degree and finish it!

The importance of being a role model

Given that I have benefitted in a life-changing way from the inspiration and opportunities provided to me by others, I have a strong desire to devote time to outreach – it is something I always hunt for wherever I am. For example, before I came to Wits University for my PhD, I was a teacher which enabled me to save up money for my postgraduate studies.  This has given me helpful experience for outreach events and inspiring others.

When I was a teacher, I would also tutor children from the local SOS children’s village where the orphaned and vulnerable children stay, giving them tutorials in maths and science and teaching them life skills– I wanted to be a role model to them like the two brothers I looked up to as a child.

Raising awareness of synchrotron techniques and GCRF START

This experience I bring to the University’s ‘Whizz Bang’ group I am part of.  Whizz Bang involves postgraduate students from the School of Chemistry and promotes science through outreach events and also school visits to underprivileged schools around Johannesburg.

At our university Energy Materials Research group events, we demonstrate a variety of chemical experiments and use the START banners in our displays to raise awareness about the important influence of synchrotron techniques on African research, especially in terms of energy materials. This is also a good way to bring attention to the many opportunities provided by START.

Sikhumbuzo Masina with members of Professor Dave Billing’s research group participating in an Energy Materials outreach event at the University of the Witwatersrand, South Africa. From left to right: Dr Caren Billing, Lesego Gaolatlhe , Adewale Ipadeola, Sikhumbuzo Masina, Adam Shnier.
Photo Credit: Dave Billing © Diamond Light Source

Investing in future African scientists, research and innovation

I believe strongly that you have to invest in science and scientists for the long-haul. If you train people and then stop investing in training and research, people lose trust and hope, and may give up. Continuity and sustainability is also lost in terms of research programmes.

I think it is vital to get people across Africa on board with GCRF START, including from smaller countries like Swaziland, Namibia and others. We need to establish links and collaborations at every level and run workshops and training. Yes, we don’t always have the instruments needed to get the preliminary data for applying for synchrotron beam time at world-class facilities like the UK’s Diamond Light Source but even collaborating with scientists from these places through a network like START can open up exciting avenues to grow, access equipment and develop the expertise to get the necessary data.

“Workshops enable us to interact with world class scientists who give us more insights into the capabilities of Diamond Light Sources and how we can apply for beamtime to probe the structure of our materials further.”

Professor Dave Billing from the University of the Witwatersrand, South Africa, speaking at the GCRF START’s Energy Materials Workshop at the University of Cape Town (15-17 Dec 2019). Photo Credit Rebekka Stredwick. © Diamond Light Source

A continuous, sustainable learning cycle

My own case demonstrates that if there is inspiration and collaboration, there is learning, and learning can be passed on! Even if students like me move elsewhere, we will stay connected because it is an ongoing collaboration we are part of. When I go back home to Swaziland, I carry on with my tutoring. I know it is time-consuming but I feel a responsibility to share my knowledge to inspire the next wave and the next wave of students, so that it is a continuous, sustainable learning cycle.

Sikhumbuzo Masina at the University of a Witwatersrand energy materials outreach event.
Photo credit Dave Billing © Diamond Light Source

Related articles

Click here to read more about the UN Sustainable Development Goals.

How to join and collaborate with GCRF START

START exerts its influence beyond the students and scientists that it directly funds, inspiring the next cohort of PhD and Postdoctoral students, developing their knowledge and skills, and enabling collaboration that can last a lifetime.

For more information about collaborating with, or joining the START programme contact the START Project Coordinator at: GCRF_START@diamond.ac.uk

My Journey to becoming a START Postdoc Research Fellow – Dr Andani Mulelu’s story

As a young structural biology research scientist, Dr Andani Mulelu has already achieved what many dream of happening in a lifetime.  His journey to becoming a GCRF START Postdoctoral Research Fellow at the University of Cape Town (UCT) is one to inspire a new generation of African scientists, showing how UK and Africa can work together to support talented individuals and excellent research with impact. Here is Dr Mulelu’s story in his own words.

Dr Andani Mulelu at the University of Cape Town.
Photo Credit: Rebekka Stredwick. ©Diamond Light Source

Dr Andani’s Mulelu’s story

I was born in the Limpopo region of South Africa to parents who had a rural upbringing under apartheid. One of four children, I soon benefited from a multitude of sacrifices made by my parents to send me to school to get a good education. My parents borrowed heavily to educate us, going without even the basics sometimes so that we might gain from every cent they made.

By the time I went to school, Apartheid had fallen, and I was sent to Zimbabwe to get an education at a boarding high school. Zimbabwe’s education was second to none in Africa and my father, who wasn’t able to pursue a civil engineering career under Apartheid restrictions, gave me the opportunities he and my mother never had.

I had a strong interest in science from an early age – at some point in high school one of my Biology teachers told us about biochemistry and I was instantly hooked! I had great teachers who motivated me and due to changing schools and countries a number of times (South Africa, Botswana and Zimbabwe), I learnt to study by myself to adapt to different curricula which set a pattern that has benefitted me to this day.  Yet school in a country rocked by economic hardship was not plain sailing. By the time my O-Levels were almost complete, I had to queue for hours to buy food because of shortages at school.

After my A-Levels, my parents had to fund my undergraduate studies at the University of Cape Town, while funding school for my siblings. A creative woman, my mother was not shy of trying new income sources and started a small business selling ‘mopane worms’, a nutritious caterpillar considered a delicacy in Southern Africa. Soon she was earning the same as my father, an engineer!

In terms of my studies, during my honours year I became fascinated by the structure of helical nitrilases, especially those that detoxified cyanide which has all sorts of potential such as cleaning up pollution from mining, and other worthy applications. Nitrilases are helical enzymes that convert nitriles to acids and/or amides (amides are organic compounds containing nitrogen).

I joined Professor Trevor Sewell’s group at UCT for my Master’s degree and my PhD and worked with an international team of scientists located in the United States, UK and Germany. This provided access to ever-improving electron microscopes to visualise our nitrilases at higher and higher resolutions.

Dr Andani Mulelu with scientists (from left to right) Priscillia Masamba,
Dr Jeremy Woodward, Melissa Marx, Philip Venter, Dr Lizelle Lubbe and
Professor Trevor Sewell at the University of Cape Town.
Photo Credit: Rebekka Stredwick. ©Diamond Light Source

The next big milestones took place after my PhD.  I was appointed a START Postdoctoral Research Fellow in the prestigious Global Challenges Research Funded programme at the University of Cape Town’s Division of Medical Biochemistry and Structural Biology (Faculty of Health Sciences). Then, working with Dr Jeremy Woodward and Angela M. Kirykowicz, we were able to visualise the structure of an intact helical filament at close-to-atomic resolution for the first time – the first high resolution visualisation of a Cryo-EM protein structure ever to be produced in Africa!

Dr Mulelu and Dr Woodward next to UCT’s cryo-electron microscope.
Photo Credit: Rebekka Stredwick. ©Diamond Light Source

The findings were published on the 17 July 2019 in Nature Communications Biology 2:260 (2019) and enabled me to finally realise my dream of visualising a nitrilase at atomic resolution and to solve the mystery of substrate selectivity in these enzymes. These results were made possible through our collaboration through GCRF START, access to the state-of-the-art eBIC facilities and expertise at the UK’s world-class synchrotron light source, Diamond.

In years to come, we hope these findings can be used to address some of the main challenges for humanity in terms of health and the environment – solutions which could contribute to meeting the key UN’s Sustainable Development goals through new ways of designing and manufacturing medicines and ‘green’ biotechnology solutions for agriculture and waste treatment here in Africa.

In addition to our successful results, I landed a job as a Research Scientist at H3D Drug Discovery and Development Centre at UCT! H3D is the first integrated drug discovery and development centre on the African continent and I am responsible for providing scientific and technical support in protein expression and purification, structural biology and running biochemical assays to increase the capacity of H3D’s Malaria and Tuberculosis (TB) target based drug discovery programs.

I can truly say that the START program has given me invaluable training and experience in structural biology, particularly in Cryo-Electron microscopy.  Although I am no longer a research scientist with START, working at H3D also brings new opportunities of continued collaboration with START.

On a personal level, the impact on my family and my future ambitions is huge. My parents are very proud of my achievements, and I thank them from my heart for their support. One of my siblings is also pursuing a PhD, and another is similarly inspired to help solve health challenges working for an NGO specialising in water supply and sanitation for disadvantaged schools.

Finally, I am financially independent! I can happily give back to support my deserving parents, and I am much closer to my long-held dream of being a world-class scientist!

Dr Mulelu visiting the UK’s Diamond Light Source synchrotron.
Photo Credit: Dr Mulelu

Related articles:

https://www.news.uct.ac.za/article/-2020-02-28-biochemistry-breakthrough-for-uct-researchers https://www.diamond.ac.uk/Science/Research/Highlights/2019/Designer-enzymes-on-the-way.htm