GCRF - START: Synchrotron Techniques for African Research and Technology

Lead Research Organisation: Diamond Light Source
Department Name: Science Division

Abstract

START is a proposal to utilise Synchrotron Techniques for African Research and Technology. It will build a partnership between world leading scientists in Africa and the UK who specialise in two strands of science; developing and characterising novel energy materials (catalysts and photovoltaics) and structural biology (understanding disease and developing drug targets). In START the research direction will be set by considering the local environment and through engagement with scientists, energy industry representatives and relevant non-governmental organisations (NGO's) across Africa.

Most importantly, START is not only about developing new energy materials or structural biology research; equally important is training the next generation of researchers and research leaders in these important areas of study. We will work together in sample fabrication and advanced characterisation through training visits between African and UK institutes. This will include experimental time at Diamond Light Source (the UK national synchrotron source) through peer reviewed access to many of the experimental facilities and in techniques that are the mainstay of understanding these materials. A major ambition of this partnership is to strengthen and broaden the network of synchrotron researchers in Africa, where there is a burgeoning ambition to exploit such facilities. This talent development will benefit the researchers themselves but also the local communities, society in general and the environment, through the reduction of burning fossil fuels and improved healthcare.

There are unique challenges to developing sustainable energy in Africa; the large fraction of off-grid consumers, the degradation of energy devices in an environment of heat and dust and the high initial capital costs for traditional installations of energy production or storage systems. Similarly challenging is addressing the health needs on the African continent, where diseases like tuberculosis and malaria negatively affect whole societies. The first step to finding and developing cures is to understand the molecular structure. Thus for both strands of research, synchrotron radiation for structure determination is at the core of scientific progress. It is critical that the countries in Africa expand their own capabilities to produce the next generation of appropriate energy materials and development of cures for relevant diseases. START aims to aid those developments through building the capacity and capability of African based scientists in both strands.

The START team is driven by the ambition to work together to solve these two strands of research, addressing some of the most pressing problems that will directly impact on peoples lives. This proposal is directly in line with the development aspirations of the African Nations who have a stated ambition to 'transform Africa from traditional to modern sources of energy and ensure access of all Africans to clean and affordable electricity' and 'Develop/implement strategies for the growth of the pharmaceutical industry in Africa'. Our aspirations are furthermore directly in line with the United Nations Sustainable Development Goals of Affordable and Clean Energy (Goal 7) and Climate Action (Goal 13) as well as Goal 3 (Good Health and Well-Being). START will help to contribute in all of these areas, which crucially underpin many of the further Sustainable Development Goals.

Planned Impact

START will be beneficial to the economic development and welfare of many countries across Africa. These countries have the stated ambition to move to economies driven by amongst others; Science, Technology and Innovation; Human Capital Development; and Infrastructural Development. START will have an impact in all of these areas, in particular in the countries involved in this partnership, namely South Africa, Lesotho, Ethiopia and Egypt. The African and UK investigators will work together to develop and characterise new materials of relevance to solar energy conversion and catalysis (strand 1) as well as to characterise proteins of relevance to better understand diseases and develop drugs (strand 2). Both are considered grand global challenges. The most promising materials and drugs will find their way into new products, commercialised by local industries (African and UK) that will directly benefit the national economies and lead to an improved energy infrastructure and healthier continent.

An equally important aspect of START is training the researchers and societal engagement that will lead to an 'inclusive and equitable quality education'; another of the stated aims of the Global Challenge Research Fund. There is a strong element of focused scientific training for the researchers but this will be supplemented by innovation and entrepreneurship training, to help them towards roles in scientific leadership as their careers develop. The unique training opportunity available at Diamond Light Source will expand the capability and numbers of researchers experienced with the characterisation techniques, essential to gain a full understanding of the novel materials and structure determination of proteins. The active outreach programme that we will implement as part of START will be another route to engage with the broader scientific community, the general public and with children. We will work together with Diamond Light Source's highly respected Communications team to present the START research and broader context of the programme at public open days, writing articles for public and general science literature, through schools talks and science fairs, website design and creating an active social media presence.

START will provide a lasting legacy; this project will kick-start lifelong collaborations for research and development of energy materials and research into drugs. The team includes investigators at all stages of their careers to provide a balance of experience, enthusiasm and ambition that will lead to a dynamic programme of research and a team that will drive forward future projects.
 
Description Presentation to STFC ODA Governance Board
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact This was the first major STFC award under the GCRF programme and as such the ways of working were developed between the grant holders and STFC. This has included developing the due diligence policy and the monitoring procedures.
 
Title MINERVA chamber 
Description A new vacuum chamber has been built that directly enables in-situ monitoring of the structural changes during growth of molecular materials studied by grazing incidence x-ray scattering techniques. 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact Papers are in preparation to identify the dynamics of growth and the effect is in-situ crystallisation. 
 
Title Protein crystallisation of pantothenamide derivates with PanK enzyme (Stellenbosch University) 
Description The PanK enzyme was expressed and purified from E.coli cells. Two different pantothenamide derivatives were incubated with PanK and the crystallisation conditions were screened against various reservoir solutions. Using the optimised crystallisation conditions, X-ray diffraction patterns were obtained. The incubated protein and as well the stock solutions were then shipped to Diamond Light Source for further experiments at the Synchrotron. 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? No  
Impact This work is ongoing, Stellenbosch University's plan is to go to the Diamond Light Source to obtain the X-ray crystal structures of our pantothenamide derivatives bound to PanK. With the protein crystallisation conditions in hand, we can now carry on to the next step in terms of obtaining X-ray diffraction patterns at the Diamond Light Source. The results will greatly help us in our understanding of how the pantothenamide derivates interact with the PanK enzyme. We can then design better pantothenamide inhibitors based on this results. 
 
Title Synthesis of phosphopantothenamide derivatives that inhibit the synthesis of acetyl-CoA in Staphylococcus aureu (Stellenbosch University) 
Description The derivatives were synthesised from commercially available precursors. The synthetic procedures were optimised over this period of time to address the underlying problems that the University has faced such as separation difficulties, purity issues and the yield of the obtained products. We are currently in the final stages of obtaining the desired final compounds. 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? No  
Impact The synthesis of the phosphopantothenamide derivatives will provide us with the necessary materials for our biochemical experiments. Some of the derivatives are costly to obtain or not commercially available thus synthesising it in-house eliminates these problems. In addition, the synthetic procedures to synthesise the derivatives can be published in a peer-reviewed chemistry journal. The synthesis of the phosphopantotenamide derivatives will be completed and the synthetic procedures will be published in a peer-reviewed chemistry journal. 
 
Description Crystallographic research - collaboration beween National Institute of Infectious Diseases (NICD) and the University of the Free State 
Organisation University of Free State, Bloemfontein
Country South Africa 
Sector Academic/University 
PI Contribution GCRF START provides funding to the two partner organisations to enable them to research using synchrotron techniques available at Diamond Light Source (through training and research investigations).
Collaborator Contribution Thandeka Moyo, Postdoctoral Research Fellow took part in a research visit to START co-investigator Dirk Opperman's laboratory at the University of the Free State, South Africa to learn specific crystallography techniques, from 28 - 30 November 2018. Dr Thandeka Moyo successfully obtained crystals which were analysed at the Diamond synchrotron on 14 December 2018. The collaboration with other START investigators at other institutes has strengthened the structural biology expertise in our laboratory. The postdoctoral fellow who has been attending all the training is now equipped with theoretical and practical experience to independently conduct X-ray crystallographic experiments. We have sent crystals to two beamtime sessions and have got diffraction data which we are currently optimizing.
Impact We aim to obtain high resolution crystal structures as our current structures are not at atomic resolution. We also aim to continue with our current collaborations and build new ones with other START co-investigators.
Start Year 2018
 
Description Crystallographic research - collaboration beween National Institute of Infectious Diseases (NICD) and the University of the Free State 
Organisation Wits Health Consortium
Country South Africa 
Sector Private 
PI Contribution GCRF START provides funding to the two partner organisations to enable them to research using synchrotron techniques available at Diamond Light Source (through training and research investigations).
Collaborator Contribution Thandeka Moyo, Postdoctoral Research Fellow took part in a research visit to START co-investigator Dirk Opperman's laboratory at the University of the Free State, South Africa to learn specific crystallography techniques, from 28 - 30 November 2018. Dr Thandeka Moyo successfully obtained crystals which were analysed at the Diamond synchrotron on 14 December 2018. The collaboration with other START investigators at other institutes has strengthened the structural biology expertise in our laboratory. The postdoctoral fellow who has been attending all the training is now equipped with theoretical and practical experience to independently conduct X-ray crystallographic experiments. We have sent crystals to two beamtime sessions and have got diffraction data which we are currently optimizing.
Impact We aim to obtain high resolution crystal structures as our current structures are not at atomic resolution. We also aim to continue with our current collaborations and build new ones with other START co-investigators.
Start Year 2018
 
Description 5th European School for Crystallography (Wolf-Dieter Schubert) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact 5th European School for Crystallography at Stellenbosch University, Stellenbosch, South Africa
Date: Wednesday, 11 July 2018
Time: 9:00 - 10:30
Title: Protein production, purification and crystallization
Time: 11:00 - 12:30
Title: Practical protein crystallization
Date: Friday, 13 July 2018
Time: 16:00 - 17:00
Title: Structure refinement, quality control and analysis.
Year(s) Of Engagement Activity 2018
URL http://www0.sun.ac.za/ecs5/
 
Description Biophysics and Structural Biology at Synchrotrons workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact This workshop was aimed at introducing young, mostly African, bioscience researchers to the power of synchrotron based facilities.

It had as its focus, the structure determination and other biophysical resources required for vaccine design, drug discovery, industrial enzymology and agrochemicals. The course traced the technology required to go from gene to the structure of proteins, as well as synchrotron based techniques for imaging cells. Topics covered included advanced strategies for crystallization, high-throughput data collection by X-ray diffraction, single particle cryo-EM, structure refinement, X-ray tomography, circular dichroism and spectroscopy. Students learned how to access synchrotron based resources and gained practical experience of working with proteins, data collection, data processing, structure interpretation and complex experimental strategies.
Year(s) Of Engagement Activity 2019
URL https://biophysicsworkshop.co.za
 
Description Carmien Tolmie attended the CCP4/MX2018 Macromolecular Crystallography School at the Institute for Physics, Sao Carlos University, Sao Carlos, Brazil from 14-24 November 2018. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Ms Tolmie (University of the Free State) presented a poster at this workshop entitled: Structure and function of Baeyer-Villiger monooxygenases from Aspergillus flavus. The other institutions that were involved are the Institute of Physics of the University of Sao Carlos, as well as the CCP4 developers.

The crystallographic school served to better the crystallographic knowledge of the three participants, to enable them to better process their crystallographic data.

Miss Tolmie will register as a START PDRA and will use the skills she obtained at the workshop to improve the processing of the crystallographic data collected during her post-doc. She will work on monooxygenases from bacterial and fungal sources as drug targets.
Year(s) Of Engagement Activity 2018
URL http://www.ifsc.usp.br/mx2018
 
Description GCRF-START kick-off meeting September 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was the first collective meeting for all START co-investigators and their Post-Doctoral assistants and some PhD students. The event was useful in introducing the management of START, setting the scene for the research in both directions - structural biology and energy materials.

Having researchers present from Africa and the UK opened opportunities for discussion and the beginnings of new collaborations were built on which are set to continue through the life of the START project.
Year(s) Of Engagement Activity 2018
 
Description Indaba 9 talk by Wolf-Dieter Schubert 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Indaba 9 (Conference by the South African Crystallographic Society)
Place: Skukuza Camp, Kruger Park, South Africa
Date: 4 September 2018
Title: Interdomain Interactions within a Multimodular Xylanase Xyl.
Year(s) Of Engagement Activity 2018
URL https://www.regonline.com/builder/site/Default.aspx?EventID=1991800
 
Description Member of council of Royal Society of South Afric - Ed Sturrock member of committee 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Member of council of Royal Society of South Africa and chaired the committee in that organised the Annual SA Schools Essay Competition, this reached a Wider South African scientific community and lay audience
Year(s) Of Engagement Activity 2018
URL http://www.royalsocietysa.org.za/?page_id=247
 
Description Pan-African Crystallography Conference (PCCr2) and second African Light Source Conference (AfLS2) talks by Wiolf-Dieter Schubert 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Joint Meeting of the second Pan-African Crystallography Conference (PCCr2) and second African Light Source Conference (AfLS2)
Place: University of Ghana, Accra, Ghana

Pre-Conference Training Workshop on Structural Biology, a tool for sustainable development in Africa, BioStruct-Africa
Date: 28 January 2019
Title: Protein production, purifcation and crystallization
Time: 11:00 - 12:00
Audience: Postgraduate students, postdoctoral fellows and faculty from various African countries.
Audience size: 30

PCCr2
Date: Tuesday, 29 January 2019
Time: 11:20 - 11:40
Title: Virulence Factors of Listeria monocytogenes
Audience: Structural Biologists (postgraduate, postdoctoral, faculty) from various African countries, Europe and South America.
Audience size: 50

AfLS2
Time: 15:40 - 16:00
Title: Bioscience Highlights from South Africa
Audience: Physicists, Material Scientists, Paleontologists mainly from African countries with some representation from European, Asian and South American countries.
Audience size: 50
Year(s) Of Engagement Activity 2018
URL https://www.regonline.com/builder/site/Default.aspx?EventID=1991800
 
Description Poster presentation by University of Cape Town - Edward Sturrock: at the Gordon Research Conference, Proteolytic Enzymes and their Inhibitors, Ill Ciocco, Italy, June 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gordon Conference - International protease and protease inhibitor communities - a forum for discussion of new findings in the developments relating to the role of proteolytic enzymes and inhibitors in health and disease. It provided opportunities for early career scientists to meet established scientists in the area.
Year(s) Of Engagement Activity 2018
URL https://www.grc.org/proteolytic-enzymes-and-their-inhibitors-conference/2018/
 
Description Presentation by University of Cape Town - Edward Sturrock: South African Society of Biochemistry and Molecular Biology, Potchefstroom, South Africa, July 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact South African Society of Biochemistry and Molecular Biology (SASBMB) conference - South African biochemistry and structural biology communities - Reaching the wider South African scientific community and lay audience
Year(s) Of Engagement Activity 2018
URL https://sasbmb.org.za/congress-2016/
 
Description Presentation on malaria drug discovery (Lauran Arendse) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Lauren Arendse is a postdoctoral candidate working under a START co-investigator she presented on current research and future plans related to structure-based malaria drug discovery at the Drug Discovery and Development Centre (H3D) Scientific Management Advisory Board meeting, University of Cape Town, November 2018.
Year(s) Of Engagement Activity 2018
 
Description Presentation, Stellenbosch (Lauren Arendse) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Lauren Arendse is a postdoc under a START co-investigator. She presented talk entitled "Dual ACE C-domain and neprilysin inhibitors for the treatment of hypertension & cardiovascular disease" at the Renin-Angiotensin-Aldosterone System Satellite Meeting 2018, 28 - 30 November, Stellenbosch 2018.
Year(s) Of Engagement Activity 2018
URL https://www.hypertension.org.za/events/2018/raas-satelite-meeting-28-30-november-2018
 
Description South African Society for Biochemistry and Molecular Biology - talk (Wolf-Dieter Schubert) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Results from the START grant were presented at
Joint meeting of the South African Society of Biochemistry and Molecular Biology (SASBMB) - Federation of African Societires for Biochemistry and Molecular Biology (FASBMB)
Title: Interdomain interactions within a multimodular xylanase Xyl
Place: North West University, Potchefstroom, South Africa
Date: 10 July 2018
Year(s) Of Engagement Activity 2018
URL http://sasbmb.org.za/congress-2016/