11th July 2017
Since the discovery of the three-dimensional structure of DNA in 1953 by James Watson and Francis Crick, molecular biologists have been studying the function of genes and genomes made up of the four bases of DNA. Scientists have had the ability to modify DNA through a number of enzymatic processes throughout recent decades, but these were mostly limited to manipulation of smaller pieces of DNA and vectors used for downstream analyses or genetic transformation of organisms.
Precise, targeted genome engineering of organisms became a reality in 2012 when it was shown that an engineered Cas9 (an RNA-guided DNA endonuclease) could be used together with components of the bacterial defense system CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). CRISPR-Cas9 has since revolutionized genome engineering in a range of organisms- including yeast, zebrafish, fruit flies, nematodes, plants, mice, monkeys and human embryos.
A handful of researchers in South Africa has since started incorporating this, and other genome-engineering technologies, in their research endeavors. Considering the potential impact of this technology and its ability to address African research questions, it was appropriate to incorporate as the central theme in one of the series of ACGT regional scientific fora. The ACGT teamed up with the University of Pretoria to host a “Genome Editing” forum that cut across multiple biotechnology sectors.
The forum was anchored by a leading genome editing specialist in the plant biotechnology sector, from the Karlsruhe Institute of Technology (KIT) in Germany, Professor Holger Puchta. Prof Puchta is the leader of the Botanical Institute at the research entity and Chair in Molecular Biology and Biochemistry. Professor Puchta’s keynote presentation was entitled “Double-Strand Break Induced Genome Engineering in Plants: Past, Present, Future”. The remainder of the presentations were from South African-based researchers and included:
- Ms Prashika Singh (Wits)- Using obligate heterodimeric TALENs to mutate Hepatitis B virus DNA
- Prof Patrick Arbuthnot (Wits)- Disabling Hepatitis B virus with CRISPR/Cas9 from Staphylococcus aureus
- Dr Victoria Maloney (UP)- CRISPR gene editing in trees
- Mr Donovin Coles (UP)- Lessons learned from genome editing in Arabidopsis thaliana
- Mr Ezio Fok (CSIR)- Interrogating the dark matter of the genome using gene editing tools.
The presentations were all of an exceptionally high standard and feedback received from delegates was very positive. Sufficient time was was set aside for networking between sessions and following conclusions of the event over lunch.
The event attracted a total of 61 delegates, including principal investigators and post-graduate students, with some as far afield as Cape Town. Notably, there was also representation from two entities in industry. From the deliberations, it was clear that researchers in different biotechnology sectors could benefit strongly from networking and collaboration with researchers in other sectors, should cross-cutting technologies be the central focus.
The ACGT and its partners are currently evaluating how best to build capacity in this developing field in the country. What is certain is that more events on this exciting and rapidly evolving topic will be forthcoming.
The ACGT wishes to express its sincere gratitude to especially Mr Thabo Khoza and Itseng Malao (both ACGT) as well as Dr Bridget Crampton for co-organizing the event; and the University of Pretoria for acting as hosts.
6th June 2017
A whole transcriptome sequencing (or RNA sequencing/RNA Seq) data analysis workshop was hosted for ACGT researchers from 15-19 May. The workshop was hosted by ACGT and facilitated by expert trainers from the University of Pretoria’s Centre for Bioinformatics and Computational Biology (CBCB, Prof Fourie Joubert) and the Agricultural Research Council’s Biotechnology Platform (Dr Charles Hefer and Dr Oliver Bezuidt).
RNA Seq aims to unravel the sum of all transcripts in an organism at any given moment in time and is a key intermediate step in the central dogma. The coverage of the technology is also still superior to technologies aiming to measure the full complement of proteins and metabolites in a living system, but at the same time further removed from the phenotype of an organism. Hence, transcriptome analysis can give important clues to changes occurring in an organism following a variety of environmental cues or life stage transitions.
The technology can be applied across multiple fields of study, and interest for the course was received from researchers and institutions with very different backgrounds and research aims. A total of 23 delegates could be accommodated for the week-long training event, hailing from the ARC (several different institutions), National Health Laboratory Service (NHLS), National Institute for Communicable Diseases (NICD), University of Pretoria (several medical, veterinary and agricultural delegates), as well as the University of the Witwatersrand.
The workshop included a mix of lectures and hands-on practical sessions in the CBCB training laboratory. Delegates were given a holistic view of all the aspects contributing to a successful transcriptome analysis, including coding in Linux, computing clusters as well as an introduction to next-generation sequencing (including experimental design, quality control and sequence alignment). A whole day was dedicated to analysing differential expression, and the last day was set aside for specific one-on-one sessions with delegates to address their specific queries or to clarify any issues that may have arisen.
Even though delegates were at very different levels in their experience with application of RNA Seq analysis, the feedback received following conclusion of the course was very positive. A possibility for future training events may be to split delegates into a beginners and advanced course, since interest in this specific course has always been high.
The ACGT would like to again thank the course facilitators for the immense effort and time invested in training partnership researchers.
23rd May 2017
The ACGT, UP and CSIR recently hosted an Introduction to Proteomics Workshop which ran from the 11th to the 12th of May 2017 at the University of Pretoria Medical School. The workshop was in response to the “Workshops and Training Needs” survey that was sent out to the ACGT in which an introductory proteomics workshop was highlighted as a need.
The workshop was attended by researchers new to the field of proteomics. Delegates hailed from the University of Pretoria (UP), the Agricultural Research Council, the University of the Witwatersrand as well as Vaal University of Technology and Cape Town University.
Dr Stoyan Stoychev (Council for Scientific and Industrial Research, CSIR) and Prof Duncan Cromarty (UP Immunology) lead the team of researchers who facilitated the workshop. The first day of the workshop was facilitated by Ms Chanelle Pillay (UP), Dr Previn Naiker (CSIR), Prof Cromarty and Dr Stoychev. The second day was facilitated by Ms Kim Sheva (UP), Ireshyn Govender (CSIR) and Dr Stoychev. Topics covered included: mass spectrometry basics, proteomics experimental design and sample preparation, mass spectrometry-based workflows, MALDI-IMS, as well as data processing and interpretation. The delegates also got a chance to discuss their individual projects with the facilitators as well as complete a group assignment in which they were given different proteomics scenarios to work through. All the workshop facilitators have been through extensive Proteomics training provided by Prof Katherine Lilley and Prof Lennart Martens over the past four years and Dr Stoychev and Prof Cromarty are leading proteomics researchers in South Africa.
The ACGT will be hosting a more advanced proteomics course later in the year (11-13 October 2017) which will focus on post translation modification phosphorylation and protein structural characterisation using HDX-MS. The facilitating team will be led by Prof Ole Jensen from Denmark. More information regarding this workshop will be circulated on the ACGT mailing lists.
Some feedback from the workshop:
- I would highly recommend this course to other young researchers because there were factors in a scientist’s research that were discussed starting from the sampling to data analysis. Although it was mainly based on proteins, the workshop was also open to other ideas. The facilitators were experts. Therefore, they were able to touch on every aspect and provide answers to difficulties encountered by researchers. Lastly, the workshop offered us an opportunity to engage with other colleagues that we didn’t imagine that we will meet with along the way. It was a great opportunity to establish collaboration and make contact with each other.
- It (the workshop) provided a well-elaborated introduction to proteomics, theoretically and practically, and has allowed for a more focused approach to my research and the consideration of even better options for data analysis and presentation.
- The presenters and organisers were very welcoming, patient, informative and open to any questions and clarifications. It created a great atmosphere for learning.
9th May 2017
A highly successful Metabolomics workshop was hosted by the ACGT and the University of Johannesburg from 6 to 10 March 2017 at the University of Pretoria’s Centre for Bioinformatics and Computational Biology (CBCB). This event built on the first open-source metabolomics workshop, also facilitated by ACGT and UJ in 2016, and is based on the European EMBL course.
A number of European metabolomics experts returned to facilitate the event, and a number of new experts also joined the facilitation team. These included (Europe): Dr Reza Salek (University of Cambridge), Drs Karl Burgess, Naomi Rankin and Justin van der Hooft (University of Glasgow), Dr Jos Hageman (Wageningen University) and Dr Fabien Jourdan (INRA, France). Local trainers included Drs Fidele Tugizimana and Edwin Madala from the University of Johannesburg.
The theme of the workshop was Study Design, Informatics and Statistics and included numerous lectures as well as hands-on data analysis and statistics sessions. An internet-based participatory quiz at the end of each session allowed participants to test their knowledge in a very informal manner, and was received very well by the delegates.
The response to the workshop registration was overwhelming and not all delegates could be accommodated due to space constraints. Those who did take part in the workshop were representative of four of the five ACGT partner institutions and included principal investigators (UP, Wits, UJ) as well as post-graduate researchers (UP, CSIR and UJ).
Feedback received from the delegates was extremely positive. Herewith a few quotations from attendees:
- It provides a week-long introduction to all the core concepts in Metabolomics. Both inexperienced and experienced practitioners of Metabolomics can benefit from attending the course.
- The workshop facilitators were very professional; they also provided a lot of expert knowledge and guidance on metabolic analysis. They provided iterative educational activities and the workshop was wholly enjoyably.
- ACGT deserves a medal for presenting course relevant to staff and students to increase the odds for success.
Metabolomics is a growing field in the partnership and country and following the Pretoria event, the facilitators hosted a shortened version of the workshop in Cape Town, at the University of Cape Town; where they were hosted by Professor Jonathan Blackburn.
Feedback from this event is being utilized to plan a training workshop in the field for 2018. It will in all likelihood be facilitated during the first quarter of 2018. Further news of the event will be circulated in due course.
The Centre would like to thank ThermoFisher and the French Embassy for financial assistance to enable the travel of Drs Karl Burgess, Naomi Rankin and Fabien Jourdan.
The Centre would also like to thank especially Dr Farhahna Allie and Ms Itseng Malao for organizing the workshop; and the facilitators for their time and effort invested in training South African researchers.
9th March 2017
The Centre secured a metagenomics expert for a national metagenomics symposium, which was hosted on the 23rd of November 2016. Professor Peter Golyshin (Bangor University, Wales) is a well-known international metagenomics expert and agreed to be the keynote at the national event held at the Department of Science and Technology (DST). A number of national institutions and prominent local researchers were also represented (69 in total), including the Universities of Pretoria, North-West, Cape Town, the Western Cape, VUT, TUT, UNISA, the ARC as well as the CSIR. Research from the CSIR, UP, NWU, UWC as well as UCT was showcased at the event. The symposium ended with a discussion about collaborative opportunities in the field, and it was agreed that the ACGT would make available the research interests, expertise and relevant infrastructure of those in the field of metagenomics on its website.
9th February 2017
A detailed three-day open-source proteomics workshop focusing on targeted proteomics and the use of the software package Skyline (this software package can be utilised regardless of hardware utilised in the different institutions and has become highly popular in the proteomics community) was hosted from the 6th to the 8th of December 2016 at the University of the Witwatersrand. The workshop was conducted by Mr Brendan MacLean (who is the chief developer of the software) and Mr Brian Searle (both from the MacCoss lab, Washington University) as well as Dr Birgit Schilling (Gibson lab, Buck Institute). Both institutes are located in the United States. Various advanced topics were covered during the three-day workshop, and delegates from multiple institutions attended. Invitations were also extended to proteomics researchers outside of the region, and researchers hailing from the Universities of Cape Town and Limpopo were also in attendance at the workshop.
12th January 2017
Dr Rachel Chikwamba, CSIR Group Executive: Strategic Alliances and Communication, was recently appointed to the African Union (AU) high-level committee on Science, Technology and Innovation Strategy for Africa 2024 (STISA 2024) and to the South African Medical Research Board.
Rachel will join a nine-member High-Level African Panel on Emerging Technologies, which is composed of eminent experts who advise the AU and all its affiliates on harnessing emerging technologies.
In June 2014, the AU adopted a long-term STISA 2024 roadmap to underpin its Agenda 2063, with its main drive as the diversification of sources of economic growth and lifting the continent’s population out of poverty. The strategy aims to foster social and economic transformation by developing human capital, innovation, value addition, industrialisation and entrepreneurship.
STISA 2024 has identified six priority areas namely: Eradicating hunger and ensuring nutrition and food security; prevention and control of diseases and ensuring wellbeing; communication (physical and intellectual mobility); natural resources management and climate change; peace and security and wealth creation. A major recognition in STISA 2024 is that the continent needs to apply existing and emerging technologies to realise the AU vision.
Rachel will also serve on the South African Medical Research Board for the period 2016 to 2019 together with 15 other distinguished leaders.
Story by: Anna Semenya, CSIR News
7th December 2016
The ACGT, in conjunction with the CSIR, hosted the 12th Regional Plant Biotechnology Forum on the 8th of September at the CSIR’s International Convention Centre (ICC). The forum focused on “Plant-based biologics” and saw over 50 delegates in attendance.
The forum kicked off with Dr Rachel Chikwamba, CSIR Executive for Strategic Alliances and Communications, giving a brief welcome and introducing the forum’s key-note speaker, Professor Herta Steinkellner. Herta is a professor at the University of Natural Resources and Life Sciences (BOKU) in Vienna, Austria. She has expertise in N-glycosylation in plants, recombinant protein production in plants as well as protein glycan engineering. She gave a presentation titled “In planta engineering of post-translational protein modification to enhance biological activity”, which was very well received by the audience and sparked interest in future collaborations between her institution, BOKU, and the CSIR.
Other contributors to the forum included CSIR’s Dr Tsepo Tsekoa and Dr Maretha O’Kennedy, Dr Priyen Pillay from the University of Pretoria and Dr Mauritz Venter from the biotechnology company Azargen. Dr Tsekoa’s presentation was on plant-made antibodies for passive immunisation, while Dr O’Kennedy gave a talk on affordable plant-produced vaccines and biologics through innovative science. Dr Pillay gave a talk on his PhD work, performed at the University of Pretoria, which focused on the contribution of agrofiltration to VP1 recombinant protein degradation. Dr Venter, co-founder and CEO of AzarGen Biotechnologies, gave a talk on “Entrepreneurial endeavours in Plant Biotechnology” and took the audience on a very entertaining journey of how he started his own successful biotechnology company.
The ACGT partner institutions were well represented by the delegates that attended the forum. Delegates were mostly from the ACGT partner institutions (CSIR, UP, ARC and UJ) but also affiliated with the following: Onderstepoort Biological Products (OBP), the Technology Innovation Agency (TIA) and the University of South Africa (UNISA). The forum provided an opportunity for collaborative talks to be initiated between the CSIR, BOKU and Azargen. Potential synergies between these and other research institutions will be evaluated and exploited where possible.
Story by: Thabo Khoza for ACGT
1st December 2016
A new study is the first to show that living organisms can be persuaded to make silicon-carbon bonds—something only chemists had done before. Scientists at Caltech “bred” a bacterial protein to have the ability to make the man-made bonds, a finding that has applications in several industries.
Molecules with silicon-carbon, or organosilicon, compounds are found in pharmaceuticals as well as in many other products, including agricultural chemicals, paints, semiconductors, and computer and TV screens. Currently, these products are made synthetically, since the silicon-carbon bonds are not found in nature.
The new research, which recently won Caltech’s Dow Sustainability Innovation Student Challenge Award (SISCA) grand prize, demonstrates that biology can instead be used to manufacture these bonds in ways that are more environmentally friendly and potentially much less expensive.
“We decided to get nature to do what only chemists could do—only better,” says Frances Arnold, Caltech’s Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry, and principal investigator of the new research, published in the Nov. 24 issue of the journal Science.
The study is also the first to show that nature can adapt to incorporate silicon into carbon-based molecules, the building blocks of life. Scientists have long wondered if life on Earth could have evolved to be based on silicon instead of carbon. Science-fiction authors likewise have imagined alien worlds with silicon-based life, like the lumpy Horta creatures portrayed in an episode of the 1960s TV series Star Trek. Carbon and silicon are chemically very similar. They both can form bonds to four atoms simultaneously, making them well suited to form the long chains of molecules found in life, such as proteins and DNA.
“No living organism is known to put silicon-carbon bonds together, even though silicon is so abundant, all around us, in rocks and all over the beach,” says Jennifer Kan, a postdoctoral scholar in Arnold’s lab and lead author of the new study. Silicon is the second most abundant element in Earth’s crust.
The researchers used a method called directed evolution, pioneered by Arnold in the early 1990s, in which new and better enzymes are created in labs by artificial selection, similar to the way that breeders modify corn, cows, or cats. Enzymes are a class of proteins that catalyze, or facilitate, chemical reactions. The directed evolution process begins with an enzyme that scientists want to enhance. The DNA coding for the enzyme is mutated in more-or-less random ways, and the resulting enzymes are tested for a desired trait. The top-performing enzyme is then mutated again, and the process is repeated until an enzyme that performs much better than the original is created.
Directed evolution has been used for years to make enzymes for household products, like detergents; and for “green” sustainable routes to making pharmaceuticals, agricultural chemicals, and fuels.
In the new study, the goal was not just to improve an enzyme’s biological function but to actually persuade it to do something that it had not done before. The researchers’ first step was to find a suitable candidate, an enzyme showing potential for making the silicon-carbon bonds.
“It’s like breeding a racehorse,” says Arnold, who is also the director of the Donna and Benjamin M. Rosen Bioengineering Center at Caltech. “A good breeder recognizes the inherent ability of a horse to become a racer and has to bring that out in successive generations. We just do it with proteins.”
The ideal candidate turned out to be a protein from a bacterium that grows in hot springs in Iceland. That protein, called cytochrome c, normally shuttles electrons to other proteins, but the researchers found that it also happens to act like an enzyme to create silicon-carbon bonds at low levels. The scientists then mutated the DNA coding for that protein within a region that specifies an iron-containing portion of the protein thought to be responsible for its silicon-carbon bond-forming activity. Next, they tested these mutant enzymes for their ability to make organosilicon compounds better than the original.
After only three rounds, they had created an enzyme that can selectively make silicon-carbon bonds 15 times more efficiently than the best catalyst invented by chemists. Furthermore, the enzyme is highly selective, which means that it makes fewer unwanted byproducts that have to be chemically separated out.
“This iron-based, genetically encoded catalyst is nontoxic, cheaper, and easier to modify compared to other catalysts used in chemical synthesis,” says Kan. “The new reaction can also be done at room temperature and in water.”
The synthetic process for making silicon-carbon bonds often uses precious metals and toxic solvents, and requires extra processing to remove unwanted byproducts, all of which add to the cost of making these compounds.
As to the question of whether life can evolve to use silicon on its own, Arnold says that is up to nature. “This study shows how quickly nature can adapt to new challenges,” she says. “The DNA-encoded catalytic machinery of the cell can rapidly learn to promote new chemical reactions when we provide new reagents and the appropriate incentive in the form of artificial selection. Nature could have done this herself if she cared to.”
The Science paper, titled “Directed Evolution of Cytochrome c for Carbon-Silicon Bond Formation: Bringing Silicon to Life,” is also authored by Russell Lewis and Kai Chen of Caltech. The research is funded by the National Science Foundation, the Caltech Innovation Initiative program, and the Jacobs Institute for Molecular Engineering for Medicine at Caltech.
Story by: Whitney Clavin for Caltech
16th November 2016
The developing world is achieving significant growth in a broad cross-section of biotechnology fields, many of them directly tied to food production, health and other dimensions of human well-being, says a new analysis commissioned by the CAS-TWAS Centre of Excellence in Biotechnolgy.
The first-of-its kind report, ‘Biotechnology in Developing Countries: Growth and Competitiveness’ was released today by the Beijing-based centre, which is organized by the Chinese Academy of Sciences (CAS), and The World Academy of Sciences (TWAS). The CAS-TWAS Centre of Excellence for Biotechnology report provides an assessment of research and patents in the field across the global South.
“This report is, to the best of my knowledge, the first extensive document summarizing the development status of a specific technology area in the developing world,” writes Bai Chunli, the president of both CAS and TWAS, in the foreword. “It provides a strong, valuable assessment of biotechnology activities in developing countries, as measured in scientific publications and patents.”
Simultaneously, it highlights the important role of international collaboration in the rapid pace of growth in the field, especially in sub-Saharan Africa.
The report found that from 2004 to 2015:
- Biotechnology research has grown steadily, with a 117% increase in published studies. However, biotechnology research from the developing world is less cited in other research papers – only about 83% as much.
- Over 85% of the biotech papers that were co-authored by science-and-technology lagging countries resulted from international collaborations. Countries in sub-Saharan Africa in particular benefited from international collaboration, resulting in a notably high impact.
- Patent filings in the developing world have been most active in industry, food and environmental biotechnology sectors. Most of those patents have been new enzymes, totalling 79,694 – comprising of more than 40% of the overall patents.
- China leads in biotechnology papers produced in the ten-year period with 78,263, followed by India with 24,081 and Brazil with 17,769. It also leads all countries with 149,339 patent families, followed by India with 15,420 and Mexico with 14,574
As a critical driver of science that boosts food resources, improves nutritional health, and battles environmental pollution, biotechnology is one of the most productive research fields of our time. The report broadly surveys research and development work in biotechnology carried out from 2005 to 2014.
Bai said the report could be valuable to governments and policymakers, as well as related research sectors, industry sectors and international bodies. He added that CAS and TWAS hope the report will help to nurture a flourishing biotechnology sector in all developing countries and regions.
“Embracing the great opportunities of the emerging bio-economy, developing countries need to sharpen their awareness, increase their commitment and gradually build their own strength in the dynamic fields of biotechnology,” he writes in a foreword to the report. “Only in that way can they fully exploit its potential to drive economic growth and social development.”
The report also includes other findings: And East Asia, Southeast Asia and the Pacific Region had a particularly strong increase in biotechnology papers. That region also put out the most patents. Within biotechnology, it found, the most published field of research was infectious diseases.
The report is available online.
Story by: Sean Treacy for TWAS.ORG