Development and optimisation of thin-film photovoltaic devices (solar cells) for sustainable solar energy

Scientists in the UK’s University of Sheffield’s Electronic and Photonic Molecular Materials Group (EPMM) work on the development and optimisation of thin-film photovoltaic devices (solar cells) for sustainable energy solutions. The advantage of these type of devices is that they can convert sunlight to electrical power with high efficiency, with such materials being easy and cheap to process, potentially allowing ‘sustainable’ solar cells to be manufactured at high volume and low cost. This is important given the rising global energy demand and need for electrification in remote, rural areas, particularly in Africa, where national grids are often over-constrained.

The EPMM Group, which collaborates with the GCRF START grant, focuses on two classes of materials: perovskites[1], [2] and polymer fullerene blends. Industry standard silicon solar cells require very high temperature processing and expensive controlled environments (clean rooms) for their manufacture, whereas hybrid-perovskites solar can be fabricated at low temperatures using liquid-based processing which reduces costs and makes their production easily scalable. However, one of the biggest challenges with these hybrid-perovskites is their reduced stability compared to silicon. The Group is therefore investigating these materials to understand how best they can be optimised for the next generation of solar energy devices.

Fig 1. This figure shows both small and large area perovskite PV devices fabricated by spray coating. The figure also shows a SEM cross-sectional image through a typical device. Part (a) shows a photograph of small and large-area fully spray-coated perovskite solar cells. Parts (b,c) show a cross-sectional SEM image of complete devices incorporating a spray-cast perovskite layer. The device in part (b) utilises spin cast SnO2 and spiro-OMeTAD layers whereas the device in part (c) is fully spray-coated. Source: Bishop, J.E., Read, C.D., Smith, J.A. et al. Fully Spray-Coated Triple-Cation Perovskite Solar Cells. Sci Rep 10, 6610 (2020). https://doi.org/10.1038/s41598-020-63674-5.

Investigating affordable energy solutions with the GCRF START grant

In their research, the EPMM scientists have benefitted from the GCRF START grant, enabling them to get involved in new international collaborations as well as access the UK’s national synchrotron, Diamond Light Source (Diamond), where they use synchrotron techniques such as X-ray scattering to research halide perovskites, a potential material for the next generation of low-cost photovoltaics.

“Using Diamond allows us to explore the structure of these materials at length-scales corresponding to atomic and molecular bonds, we have found that understanding the structure of these materials is absolutely critical in developing our understanding of how they ‘work’ in devices. Ultimately, this understanding helps in developing new materials or new ways to process existing materials to get optimum performance (efficiency) out of our solar cells.”

Prof. David Lidzey, GCRF START Co-I and Director of the EPMM Group
From left to right: Adam Shnier from the Energy Materials Research Group at the University of the Witwatersrand, South Africa, and Rachel Kilbride, Joel Smith and Mary O’Kane from the Electronic and Photonic Molecular Materials Group at the University of Sheffield, UK. The scientists are conducting wide-angle X-ray scattering measurements at the UK’s national synchrotron Diamond Light Source (Diamond). The students are using one of Diamond’s 2D X-ray detectors to monitor in-situ crystallisation and degradation processes with perovskite thin film samples held in an environmental chamber. Photo credit: Onkar Game. ©University of Sheffield / EPMM Group

The GCRF START grant has also funded Dr Onkar Game’s one-year Postdoctoral position in the EPMM Group during which time he has both undertaken his own experiments on perovskites and worked very closely with various PhD students in the Group. Prof. Lidzey reports that Dr Game’s input has been invaluable, this flexible work-pattern maximising the amount of research using the funding available.

“The GCRF START grant provided me a unique opportunity to make use of world class structural characterisation facilities at Diamond” says Dr Game. “Working with PhD student Joel Smith, we utilised the in-situ Grazing Incidence Wide Angle X-ray Scattering (GIWAXS) facility at the I22 beamline in Diamond to identify the factors affecting the degradation of perovskite crystal commonly used in perovskite-PV devices[3]. This helped us to tune the composition of perovskite crystal to make it more stable towards moisture and light induced degradation. I also enjoyed setting up the in-situ measurements with Joel on understanding of solvent-induced liquification and crystallisation of perovskite using GIWAXS on Diamond’s I07 beamline,” Dr Game adds.  

From left to right: Prof. David Lidzey and Dr Onkar Game from the University of Sheffield’s EPMM Group, UK. The scientists are investigating perovskite degradation using an environmental chamber and 2D X-ray detector on the I07 beamline at the UK’s national synchrotron Diamond Light Source. Photo credit: Joel Smith. ©University of Sheffield / EPMM Group

Collaborative research on Perovskites: the effects of composition and temperature

Dr Claire Greenland completed her PhD in the EPMM Group supervised by Prof. Lidzey. She has been working on perovskites and has been particularly interested in how the structure of such materials are affected by their composition and local temperature. This work was done in close collaboration through the GCRF START network with the Energy Materials Research Group at the University of the Witwatersrand (Wits), South Africa, led by GCRF START Co-I, Prof. Dave Billing. In this research, Claire studied one type of popular perovskite called a ‘mixed cation’ perovskite, and used X-ray scattering to characterise the structure of the perovskite as it was cooled down to very low temperature (-190 °C). She also measured the ability of the perovskite to absorb and emit light over the same temperature range. In these studies, Claire was looking for changes in the crystal-phase as the temperature was changed.

Understanding such processes is important, as the temperature at which some phase changes occur are within the expected operational temperature of the solar cell and understanding the effect on the properties of the materials in the solar cell forms a critical part of the understanding of how such materials (and devices) work.

“Interestingly, the structure of the perovskite crystal is not fixed, but can vary as a function of temperature, being ‘cubic’ at room temperature and starting to change to a ‘tetragonal’ phase around -13 °C, with a second low-temperature phase identified at -180 °C,” Prof. Lidzey explains. “Through careful analysis, these changes in crystal structure could be correlated with changes in the optical properties of the perovskite.”

This research was supported with assistance from Wits University scientist, Adam Shnier. Adam met members of the Sheffield team at a GCRF START meeting in 2018, hosted by the Energy Materials Research Group at Wits.

“Adam Shnier provided us invaluable support in the analysis of the X-ray scattering data, allowing us to understand how the crystal structure changed with temperature,” Prof. Lidzey says.With support from the GCRF START grant, Adam was able to travel to the UK in 2019 and assist us in some scattering experiments performed at Diamond and became an important part of the team.”  

“At the 2018 GCRF START meeting, I met a PhD student, Joel Smith, from the University of Sheffield who works on the same type of materials,” says Adam. “Joel and his colleagues are experienced at making high quality, efficient devices; while at Wits, we are experienced in making other materials that can be used for these devices and studying their crystal structures. As the 2019 GCRF START meeting was being held in the UK, we planned a research visit where I would spend a week working with Joel and his colleague Dr Onkar Game in Prof. David Lidzey’s laboratory at Sheffield. The purpose was to share technical knowledge. They were more than happy to share their experiences with these materials which instilled me with a plenty of ideas and information to share with my colleagues at home in South Africa.”

Adam Shnier from the Energy Materials Research Group at the University of the Witwatersrand, South Africa, visiting the UK’s national synchrotron, Diamond Light Source. Photo credit: Joel Smith. ©University of Sheffield / EPMM Group

The research was published in January 2020[4] and formed a very important part of Claire’s PhD thesis. Claire has since passed her PhD viva and has come back to Sheffield in the position of ‘University teacher’. While she is not currently working on perovskites, her knowledge of materials physics and experience in understanding complex phenomena are proving invaluable in teaching electromagnetism to 1st year undergraduate students and will also be useful in the 2nd year lab experiments that she is developing and running, says Prof. Lidzey.

‘The GCRF START collaboration enabled me to collaborate with academics from Wits University in South Africa, which greatly enriched my work due to their expertise in X-ray diffraction and crystal structure,” Claire explains.  “I collaborated mainly with Adam Shnier, who was able to computationally model the X-ray diffraction data taken at a range of temperatures on mixed cation perovskites. This modelling revealed the temperature dependence of a variety of crystal parameters, which not only allowed us to identify phase transitions in these materials but also to correlate crystal structure with photoluminescence properties.”

“I really enjoyed working with Adam, and his insight on all things related to crystal structure and phase was invaluable to my work,” Claire adds. “These studies shed light on the fundamental properties of perovskites and how these vary as a function of temperature – such studies are a key part of solar cell optimisation, because real world solar cells must operate under a wide range of temperatures. So, it’s really cool to know that this project was part of the push towards cheap and efficient solar cell materials, which are an essential part of tackling climate change.”  

Dr Claire Greenland from the University of Sheffield’s Electronic and Photonic Molecular Materials Group, UK. ©University of Sheffield / EPMM Group

Perovskite ‘healing’ for high-speed manufacture processes

PhD student Joel Smith has also been working on perovskites. Here, however, he has been interested perovskite recrystallisation processes using solvent molecules. In this process, a perovskite film is exposed to a solvent gas, with this exposure causing the solid perovskite film to melt into a different solid or liquid form. Once the gas is removed or when heated, this material crystallises back into a ‘healed’ perovskite. The advantage of this process is that the quality of the perovskite film can be substantially improved. Practically, this could be used to improve the quality of perovskite films deposited in a high-speed manufacture process such as spray coating.

The first part of this work was led by Dr Onkar Game and investigated how treatment with one type of solvent had some unexpected effects on the perovskite film microstructure. This included measurements on thin films at Diamond to understand how these changes in microstructure affected the perovskite’s ability to withstand different challenging environments3. As part of his PhD, Joel undertook experiments at Diamond where he used X-ray scattering to monitor the very rapid changes in the structure of the perovskite film as it turned into a liquid and then back into the perovskite.

“Here we were able to resolve crystal structures of new intermediate compounds that formed in the liquid, and we could evidence the improvement in crystal structure caused by the healing process,” explains Prof. Lidzey, “Importantly, we also showed that this process could be enhanced by changing the temperature at which healing took place.”

Joel is currently writing a paper on this work which has formed part of his PhD thesis. He is set to start his Postdoctoral research in Prof. Henry Snaith’s group at the University of Oxford, working on advanced perovskite solar cell devices.

“Bringing together expertise from our different institutions in the UK and Africa through collaborating with the GCRF START grant has allowed us to investigate the crystallisation behaviour and stability of perovskites in new ways at Diamond Light Source,” says Joel. “More generally, we have been able to assist each other in fabricating, characterising and understanding these materials by sharing experience and facilities. The wider START community has been valuable as a mutually supportive network for us to develop as independent researchers, and most importantly, to grow the synchrotron research community in Africa.”

Joel Smith from the University of Sheffield’s Electronic and Photonic Molecular Materials Group, UK. Photo credit: Onkar Game. ©University of Sheffield / EPMM Group

Commenting on the need for affordable, renewable energy solutions in Africa and the importance of collaboration to tackle global energy challenges, Prof. Billing said,

The synergy in GCRF START collaborations of having people from different backgrounds tackle a problem makes the solution more robust. Creativity is important to most Africans, and we need to be involved in these creative solutions. Also, if you co-develop through collaboration, you have a sense of ownership which is what we set out to do through the GCRF START grant.”

“Everything costs energy, fundamentally,” Prof. Billing adds. “Silicon uses a lot of energy in its making to make solar cells so I think the best we can do as humans is look at remediation and balance. The GCRF START grant asks us to consider questions in our research around the global challenges like: am I using components that are sustainable? Are we using elements which are abundant, affordable, and environmentally compatible? If you think about a rural village which is cooking using wood charcoal, they are energy poor and lighting will be paraffin or candles. If you can find a cheap source of energy there and you can bring in lighting, that is life changing!”

Traditional rondavel house in a rural South African village. Photo Credit: Rebekka Stredwick. ©Diamond Light Source
Adam Shnier at the University of the Witwatersrand taken in front of a Bruker D8 diffractometer which he uses in the analysis of thin film materials. Photo credit: Adam Shnier. ©Diamond Light Source

Read more about the Sustainable Development Goals for Energy (SDG 7).


[1] Here, “perovskite” is a name for a class of crystalline material, and there are many different combinations of starting materials that can be used to make a perovskite. Some of these materials absorb sunlight more efficiently, and others have greater environmental stability (both important characteristics for practical applications of solar cells).

[2] Bishop, J.E., Read, C.D., Smith, J.A. et al. Fully Spray-Coated Triple-Cation Perovskite Solar Cells. Sci Rep 10, 6610 (2020). https://doi.org/10.1038/s41598-020-63674-5. This work demonstrates the possibility for spray-coating to fabricate high efficiency and low-cost perovskite solar cells at speed.

[3] Onkar S. Game, Joel A. Smith et al.  Solvent vapour annealing of methylammonium lead halide perovskite: what’s the catch? J. Mater. Chem. A, 8, 2020, 10943-10956 DOI: 10.1039/D0TA03023F 

[4] Greenland, Claire, Adam Shnier, Sai K. Rajendran, Joel A. Smith, Onkar S. Game, Daniel Wamwangi, Graham A. Turnbull, Ifor DW Samuel, David G. Billing, and David G. Lidzey. “Correlating Phase Behavior with Photophysical Properties in Mixed‐Cation Mixed‐Halide Perovskite Thin Films.” Advanced Energy Materials 10, no. 4 (2020): 1901350 (https://doi.org/10.1002/aenm.201901350)

Biochemistry and X-rays, neutrons and advanced computing

“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).

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

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.

Fig.1. A glutaramide substrate bound in the active site pocket of a modified thermostable amidase as visualised using ID04-1 at the UK’s national Diamond Light Source synchrotron. The cysteine normally found at position 146 has been replaced by an alanine – thus deactivating the enzyme and enabling the bound substrate to be visualised. ©Trevor Sewell. PDB ID: 6YPA; authors: Sewell, B.T., Su, S., Venter, G., Makumire, S. (2020). The C146A variant of an amidase from Pyrococcus horikoshii with bound glutaramide. DOI: 10.2210/pdb6ypa/pdb

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.

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

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

Studying the EatA protein passenger domain of enterotoxigenic Escherichia coli (ETEC) bacteria – a cause of disease amongst children in developing countries

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).

Maria Hamunyela is a technologist at the University of Namibia, and a PhD student in the structural biology research group at the University of Pretoria, South Africa. Photo credit: Maria Hamunyela. ©Diamond Light Source

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.

Child in a South African village. Photo credit: Rebekka Stredwick. ©Diamond Light Source

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.

Maria Hamunyela is a technologist at the University of Namibia and a PhD student in the structural biology research group at the University of Pretoria, South Africa. Photo credit: Maria Hamunyela. ©Diamond Light Source

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         

Disentangling the neuromolecular networks involved in speech and language

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

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

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

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

Piecing together neuromolecular complexes and networks

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

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

FOXP2 protein – the “the language gene”

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Read more about the UN’s Sustainable Development Goals here


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

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

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

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

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

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

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

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

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

Engineering sustainable solutions – Enzymes to tackle toxic waste

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

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

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

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

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

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

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

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

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

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

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

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

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

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

About Lenye Dlamini

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


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

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

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

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

My love for science and medicine

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

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

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

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

Re-training as a protein crystallographer

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

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

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

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

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

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

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

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

Acknowledgements  

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

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

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

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

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

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

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

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

Read the full story here 

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