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  • New study on plant speciation

    27th Feb 2014

    A new study by a Wits University scientist has overturned a long-standing hypothesis about plant speciation (the formation of new and distinct species in the course of evolution), suggesting that agricultural crops could be more vulnerable to climate change than was previously thought.

    Unlike humans and most other animals, plants can tolerate multiple copies of their genes – in fact some plants, called polyploids, can have more than 50 duplicates of their genomes in every cell. Scientists used to think that these extra genomes helped polyploids survive in new and extreme environments, like the tropics or the Arctic, promoting the establishment of new species.

    However, when Dr Kelsey Glennon of the Wits School of Animal, Plant and Environmental Sciences and a team of international collaborators tested this long-standing hypothesis, they found that, more often than not, polyploids shared the same habitats as their close relatives with normal genome sizes.

    “This means that environmental factors do not play a large role in the establishment of new plant species and that maybe other factors, like the ability to spread your seeds to new locations with similar habitats, are more important,” said Glennon.

    “This study has implications for agriculture and climate change because all of our important crops are polyploids and they might not be much better at adapting to changing climate than their wild relatives if they live in similar climates.”

    Glennon’s study also provides an alternative explanation for why plants are so diverse in places like the Cape where the climate has been stable for hundreds of thousands of years. Although her study examined plant species from North America and Europe only, she is looking forward to testing her hypotheses using South African plants.

    Glennon’s paper has been published in Ecology Letters, a flagship journal for broad-scale ecology research.

     

    Creosote bush flower 

     

    Image: Output for Larrea tridentata (creosote bush) diploid and polyploid populations that shows that both ploidies share similar climate habitats, but differ in how they share that climate.

     

    About Dr Kelsey Glennon

    Dr Kelsey Glennon is a Carnegie Postdoctoral Fellow in Climate Change Research in the School of Animal, Plant and Environmental Sciences and the Global Change and Sustainability Research Institute at the University of the Witwatersrand, Johannesburg. She became interested in plant genetics while volunteering in the Hunter Lab at Salisbury University in her second year of college. She pursued a PhD at George Washington University in Washington, DC, studying plant hybridisation, its effects on species boundaries, and resulting conservation issues. Dr Glennon came to Wits University from a prestigious NSF Bioinformatics Fellowship at Syracuse University in New York. She is currently doing active field research on baobab trees in Limpopo Province and the medicinally important plant imphepho (Helichrysum odoratissimum purchase discount medication! generic versus name brand zoloft .

    Story by: Kanina Foss, Media Centre, University of Witwatersrand 

  • Prof Jolanda Roux receives IUFRO Scientific Award

    Prof Jolanda Roux receives IUFRO Scientific Award
    26th Feb 2014

    Prof. Jolanda Roux

    Prof Jolanda Roux from the University of Pretoria’s Forestry and Agricultural Biotechnology Institute (FABI) in the Faculty of Natural and Agricultural Sciences, was awarded the International Union of Forest Research Organizations (IUFRO) Scientific Award.

    This prestigious award, which is the highest that is given to forestry researchers, will be bestowed on her at the next IUFRO World Congress in October this year. One award is given every five years in each of nine categories and Prof Roux will receive the award for research accomplishment in the field of Tree Health.

    In 2012 Prof Roux also won the NSTF-BHP-Billiton Award (sponsored by Eskom) in the category Female Researcher who made an outstanding contribution to SETI through Research Capacity Development over the last five to ten years. In 2011 she was awarded the Queen’s Award for Forestry, by the Commonwealth Forestry Association, when she met Queen Elizabeth II. Prof Roux has received many other forms of recognition for her work, notably the DSTs Distinguished Young Women in Science Award, also in 2011.

    Prof Roux is a professor in the Department of Microbiology and Plant Pathology, a member of the management committee of FABI and the manager of the Tree Protection Cooperative Programme’s field and extension services.

    Her research focuses on tree diseases and she is particularly passionate about tree health in general and more specifically, fungi that cause diseases of trees on the African continent. She collaborates with researchers in many other parts of the world and has travelled widely to undertake her research.

    Prof Roux has published over 120 papers in her research area and has successfully supervised numerous PhD and MSc students. She serves on a number of international committees and is currently the coordinator for the Division Research Group on Forest Pathology of the International Union of Forestry Research Organisation.

    She is currently the Vice-President of the Southern African Society for Plant Pathology, serves on the editorial boards of the South African Journal of Science, Forestry and Forest Pathology, and is an honorary professor in the Chinese Academy of Forestry.

    Story by: Martie Meyer, UP News and Events, University of Pretoria

  • Tapping Into Biodiversity to Cure African Diseases (SABINA)

    Tapping Into Biodiversity to Cure African Diseases (SABINA)
    24th Jan 2014

    Tinotenda Shoko is one of many young Zimbabweans who have managed to find opportunities both outside and inside their country during times of limited resources. He joins other RISE students and faculty from Zimbabwe who have brought high levels of energy, talent, and optimism to their fields – often as true leaders in their scientific activities.

    Tinotenda began with the benefit of family models: His father taught primary school in Mutawatawa, and he is still teaching there today. On the basis of his strong performance in grades 1 through 7, Tinotenda was admitted to a mission boarding school for a four-year ordinary-level education. He was powerfully drawn to science, scoring high marks in calculus, physics, biology and chemistry. He was then admitted to advanced-level coursework for two additional years, and did well enough on his exams to gain admittance to the University of Zimbabwe in 2002.

    Despite his facility at basic science, he began to feel a tug toward the “real world” of industry. “Why?” he asked. “I thought it was more interesting, practical, and linked to the benefits that science brings to society. I saw so many people around who didn’t have enough food or money. I didn’t want to live like that, and I didn’t want other people to live like that. To me, education was a way out.”

    Even with his strong educational background and encouragement, he faced powerful competition when it came time to enter the university. “Despite the stiff competition from others who were sometimes better prepared,” he said, “I did come in at the top of my class; I had to work hard and I’m still working harder.”

    This appears to be an understatement. During his first year, Tinotenda tackled a daunting menu of pure science coursework that included genetics and molecular biology, mathematics, physical, general, organic and analytical chemistry, and cell biology and immunology. In addition, he also took agricultural economics, because of its links to practical areas, and statistics because of its central role in applied sciences. “I took 13 courses that year, 7 of which I passed with distinctions. I loved chemistry the best, and I got distinctions in physical and general chemistry.”

     

    In the second year he continued at this ambitious pace, but he moved farther in the direction of applied subjects, especially food engineering, food microbiology, food toxicology, food analysis, sensory evaluation of food, food chemistry, and biochemistry. In the third year his courses were still more applied, and included meat technology, fruits and vegetables, cereals, fats and oils, quality assurance and experimental design, product development, marketing, and industrial methods. By the time he had completed his BSc in food science and technology in 2005, he had taken 35 courses in sciences related to his major and passed 16 of them with distinction.

    After graduation, he immediately went to work for Blue Ribbon Industries, a milling company in Harare, as a quality control technician and research and development assistant. He helped develop a gluten-free flour blend that enabled individuals allergic to gluten to enjoy flour products. He did this by replacing wheat flour with a mixture of millet flour, sorghum flour, rice flour, and potato starch and determining the most appropriate ratio. The resulting flour, he said, baked and tasted just like wheat flour, although it required additional ingredients for successful bread making. He worked until 2008 at Blue Ribbon, which has since closed.

    His interest in food science and technology was already growing beyond the content of his traditional coursework. He sought out a program at the Zimbabwe Institute of Management (ZIM) where he could learn more about the business side of the food industry, and from the ZIM he earned a diploma in business administration in 2007.

    In 2008 Tinotenda continued his experience with the food industry when he took a job in Cape Town, South Africa, at a food processing company called Mexicorn that manufactures tortillas, tacos, and corn chips. As a Food Technologist, he was responsible for new product development and improving tortilla quality, including process and shelf life testing.

    With this practical experience under his belt, he was ready for more science when a new opportunity presented itself. A former lecturer, keeping track of events at RISE, heard about the SABINA network and urged him to apply for a fellowship being offered at the University of Malawi. He sent his application to Jane Morris in Pretoria and was accepted.

    “I knew my work had to be something in natural products,” he said. “I already had my objectives for the next opportunity to study.” He started working with local fruits and vegetables, with the objective of identifying their volatile flavor constituents.

    “A problem for fruits and vegetables is seasonality,” he said, “which limits when people can find them in the markets. If you’re able to identify the compounds which constitute the flavor of a food, you can take that to industrial level and synthesize the flavor in the lab, making it available to everyone all year round.” Among the fruits he studied were Mobola plum and monkey orange, using solid-phase micro-extraction. He used gas chromatography and gas chromatography coupled to mass spectrometry to identify the volatile constituents. He also worked with some vegetables, including cassava leaves, and a herbal tea, using hydro distillation methods to heat the plant material, drive out the essential oils, and collect the oils for identification by gas chromatography and gas chromatography coupled to mass spectrometry.

    Although Tinotenda has learned a great deal from his early work with foods, including his MSc research in applied chemistry, he is now aiming higher in his study of natural products. His dream is to complete a PhD on neutraceuticals, which are plant extracts that have not only flavor but potentially powerful nutritional and medicinal efficacy. The term, a conjugate of “nutritional” and “pharmaceutical,” is applied to products that range from isolated nutrients and herbal products to specific diets and processed foods. “There are so many diseases in Africa,” he said, “and medical costs are very high. There is also enormous biodiversity, and we want to tap into that to cure diseases.”

    He has written a more formal personal statement about his dream to help people who cannot afford the cost of medicines, offering them instead cheaper but still effective alternatives. “In Africa, it is known that certain plants have medicinal properties or health benefits, but the knowledge has not been harnessed. There is not much scientific evidence to establish the link between a particular biological function and the identification of the specific compounds in those plants. In fact, most knowledge about the usage of these plants has remained traditional and undocumented.”

    He put together his current educational strategy while in a short-term academic appointment at Chinhoyi University of Technology (CUT) in Zimbabwe as a part-time lecturer in food science. His responsibilities included teaching at the undergraduate level, developing learning materials, and participating in faculty seminars.

    As he was completing this appointment in his home country, he learned of the next exciting stage of his career – the opportunity to continue his research under a second RISE scholarship. Tinotenda is now entering a PhD program under SABINA, this time at the University of Pretoria in South Africa, where he can anticipate strong mentoring and cutting-edge instrumentation. He has also applied for a Washington Fellowship for Young African Leaders, with the strong endorsement of SIG.

    Once Tinotenda has earned his PhD, he looks forward to returning to Zimbabwe to apply the fruits of his research. He is confident that he will have an academic appointment and also work with Zimbabwe’s Scientific and Industrial Research & Development related organisations, focusing on product development and commercialization.

    Story: Alan Anderson, Science Initiative Group, Blog posts, January 2014

  • Launch of South Africa’s Bio-Economy Strategy – 14th January 2014

    Launch of South Africa's Bio-Economy Strategy - 14th January 2014
    15th Jan 2014

    The Minister of Science and Technology, Derek Hanekom, launched South Africa’s Bio-economy Strategy on 14 January 2014.

    The bio-economy refers to an entire innovation chain (from research and development to commercialisation) based on biological sources, materials and processes, and aimed at sustainable economic, social and environmental development.

    The science-based Bio-economy Strategy, approved by Cabinet in November last year, positions bio-innovation as essential to the achievement of government’s industrial and social development goals.  The strategy calls for industry, science councils, government departments and academia to cooperate closely to ensure that biotechnology and bio-innovations are market relevant and find easier application in South Africa.

    At the launch, Minister Hanekom said that the Bio-economy Strategy would take the National Biotechnology Strategy from 2001 to the next level, creating an enabling environment that will allow government departments, industry, venture capital and other stakeholders to move forward with initiatives that will be able to meet the challenges and embrace the opportunities of the future.

    “We are confident that the strategy we are launching today will address the full value chain, going beyond the mere generation of new technologies to ensuring that technology development is informed by the needs of the country and people, and that social and economic value is generated.  If we look at the sustainable utilisation of resources and encourage role players to work together to achieve common goals, we will be helping to close the innovation chasm,” Mr Hanekom said.

    “Our aim is to grow the bio-economy through strengthened partnerships with industry, and to extract the full potential of our living systems through the application of our collective competencies and capabilities.  The benefits to society will include the more sustainable use of resources, the development of new products, and improved job prospects,” he added.

    The Bio-economy Strategy is aligned to the National Development Plan, which considers science, technology and innovation key to the South African developmental agenda, as advances in these fields underpin advances in the economy and in society.  It is expected that by 2030 biotechnology and bio-innovation will be making a significant contribution to South Africa’s gross domestic product through the creation of bio-based services, products and innovations, intellectual property management and support for bio-entrepreneurs.

    In addition, the strategy recognises and builds on the important contributions that indigenous knowledge can and should play in the development of our bio-economy, and the important developmental contributions of this interface.

    South Africa has a comparative advantage because it is the third most biologically diverse country in the world, with almost 10% of the world’s known plant species and 15% of all known coastal marine species, as well as nine unique vegetation types, of which three have been declared global biodiversity hotspots.  It is also home to one of the world’s six floral kingdoms, the Cape Floristic Region.  Combined with the country’s wealth of indigenous knowledge and its established biotechnology capacity, South Africa’s biodiversity is one of the country’s greatest assets.

    The Bio-economy Strategy builds on the Department of Science and Technology’s National Biotechnology Strategy and Ten-Year Innovation Plan for South Africa, driving the development of a bio-economy in which the biotechnology sector, the information and communication technologies sector, environmental agencies and the social sciences create holistic solutions for the agriculture, health and industry.

    Source: The Department of Science and Technology, January 2014

  • Prize-Winning Studies of the Tea Plant (SABINA)

    8th Jan 2014

    The more we learn about living things, the more complex they seem. New discover to have gained speed with the unfolding of molecular genetics and the understanding that most biological functions are determined by the order of chemicals that make up our DNA. Many features of this complexity continue to baffle us: Why should we clever humans have around three million pairs of these DNA chemicals when the “simple” tea plant we cultivate for our pleasure has about a million more?

    Pelly Malebe’s curiosity as a young child inclined her toward questions like this, and she realized early that the answers to many of those questions about how life “works” could be found in her school books, especially those explaining biology, and, when she was a little older, genetics. She was drawn to the challenge of understanding the most intricate structures of living systems, and then of how they worked.

    Today as a young adult and member of RISE-SABINA, she is even more deeply involved in such questions. Under the guidance of Professors Zeno Apostolides and Zander Myburg, she is pursuing her PhD in the University of Pretoria’s biochemistry department, where she has become adept at the advanced technologies used to identify, quantify, and replicate the DNA-based genes of organisms. One of her most useful tools is a biochemical technology called the polymerase chain reaction (PCR), by which she has learned to amplify copies of particular DNA sequences, each of which may include one or more fragments of genes.

    Because of the department’s longstanding work on the biochemistry of the tea plant, Camellia sinensis, Pelly has joined in the same pursuit – specifically in exploring the genetic makeup of tea in hopes of identifying new drought-resistant varieties, which are urgently needed in dry southern Africa. Whether or not the African climate changes in the direction of lower rainfall, as many scientists have predicted, drought has long been a barrier to the production of tea crops. In fact, there is a strong correlation between some of the most popular strains, or cultivars, of tea and a low tolerance for even moderate degrees of drought.

    When tea plants are faced with a period of light rainfall, they use a number of tactics to survive:

    •  Dropping leaves
    •  Closing the stomata of the leaves, which slows or blocks photosynthesis
    •  Constricting the main stem, which reduces plant function
    •  Accumulating starch in the roots, a survival measure stimulated by harsh conditions
    •  Superoxide dismutase (detoxifying)

    Virtually all of these tactics reduce the tea plant’s value as a commercial crop. These tactics, like virtually every aspect of the plant’s life, are determined by the complex tea genome, or genetic makeup, which is the frontier Pelly is exploring. In particular, she is seeking techniques to protect tea plants against drought that do not also reduce its ability to produce tasty tea. Even more desirable are drought-resistant, desirable cultivars that also have genes that can resist multiple pests and respond to cultivation in other positive ways.

    Knowing that DNA composition varies among different cultivars, and that these molecular differences can now be detected by laboratory technologies, she has painstakingly learned modern techniques for searching out the distinctive patterns or molecular “markers” for such behaviors, beginning with drought tolerance. She is also alert for markers that indicate other desirable traits and that may be molecular neighbors of the drought tolerance markers. In this way, she hopes that the tea plant will offer signals that allow the tea grower to take advantage of any number of plant behaviors that bring advantages to the grower – and sipper.

    Like other plant research, Pelly’s study of tea relies on a close partnership between researchers in the lab and those in the field. One advantage of RISE is that such partnerships are often easy to arrange. In the case of tea, Pelly has been collaborating for several years with Nick Mphangwe of Malawi, who has already earned his PhD at the University of Pretoria and now spends most of his time at the Tea Research Foundation of Central Africa’s  center in Malawi. At TRFCA, cultivars that show good drought resistance are identified in the field. DNA samples are then harvested from those particular plants and transported to the Pretoria lab for genetic analysis. In addition to Nick’s field work in Malawi, Pelly also makes use of the university’s own smaller tea fields at the University of Pretoria, where the traits of these and other cultivars are studied.

    Since beginning her master’s work in the RISE program, Pelly has pinpointed a section of tea DNA that is associated with drought tolerance. This section, which is 1200 base pairs long, is identified in the lab with the help of a process called electrophoresis (electro plus migration). The process begins with the preparation of agarose, one of the components of agar, a valuable component of algae that is harvested along the beaches in Tanzania, Kenya, and elsewhere (and studied in the WIO-RISE network). To make this gel, the agarose is extracted from the agar, dried to a powder, mixed with hot water, and cooled. When the agarose gel is cut into slabs, mixtures of DNA, RNA, and other large molecules can be placed on it and made to move, or “migrate,” through the gel matrix by application of an electrical field. Because small fragments move faster than large ones, the fragments can be identified according to their size, with those of the same length gathering as distinct visible “bands” in the gel. The formation of a band of fragments matching the length of the marker for drought resistance tells the geneticist that this plant is drought-resistant; the marker does not appear in drought-susceptible cultivars.

    For her work in developing a method for screening tea cultivars for drought tolerance, completed during her MSc studies, Pelly and Prof. Apostolides were awarded a provisional patent. The potential outputs of their work are robust molecular markers that can be used in a selection process to improve tea yields throughout the global tea industry. Pelly’s focus is on increasing the understanding of the genetic basis of drought tolerance in plants, which may lead to other drought-tolerant crop varieties and thus to improved food and job security.

    The final filing of the patent is underway with the African Regional Intellectual Property Organization, and also in India, Sri Lanka, China and South Africa, other leading tea producers. According to the wording of the patent application, the techniques developed at Pretoria include “the steps for providing plant material to be screened; extracting genomic DNA from the plant materials; and selectively amplifying the portion of the genomic DNA coding for drought tolerance.”

    In the future, Pelly has several objectives. The first is developing the use of genetic markers for decision making and for conserving the crop plant germ plasm. Another is to develop marker-assisted selection for drought tolerance, yield, and quality, all of which have great potential value for the tea breeding industry. Finally, she hopes to use marker data to find associations with other traits of economic importance, which “may be useful to tea breeders world-wide.”

    Pelly has already received much recognition for her work. As a bachelor’s student in human genetics and a master’s student in biotechnology, she was employed by the University of Pretoria as a teaching assistant, and elected to membership in the Golden Key International Honor Society. After she began her PhD work at Pretoria, she was funded not only by RISE through SABINA, but also by the South African National Research Foundation’s Innovation Doctoral Scholarship.

    In addition, she was given a South African Women in Science Award (WISA) by the Department of Science and Technology. This award was created to recognize and reward the achievements of women scientists and researchers in South Africa, and also to dispel the myth that science is for men only. The DST hopes that the achievements of the award winners will encourage other women to persevere in overcoming gender discrimination to contribute to research and knowledge generation.

    Story: Alan Anderson, Science Initiative Group, Blog posts, December 2013

     

  • Two UP professors elected to International Society for Plant Pathology

    Two UP professors elected to International Society for Plant Pathology
    6th Nov 2013

     

    At the recent International Society for Plant Pathology (ISPP) meeting in Beijing it was announced that two South Africans (both from the University of Pretoria’s Faculty of Natural and Agricultural Sciences), Prof Brenda Wingfield and Prof Lise Korsten were elected to the ISPP Executive Committee. Their term of office is from 2013 until 2018.

    Prof Wingfield was elected as the Secretary General while Prof Korsten as the Global Food Security Task Force Chair of the ISPP. The International Society for Plant Pathology promotes the world-wide development of plant pathology and the dissemination of knowledge about plant diseases and plant health management.

    The Society also sponsors the International Congress of Plant Pathology (ICPP) at regular intervals and other international meetings on plant pathology and closely related subjects. The Society establishes committees to consider and report on special fields or problems in plant pathology. The Society organises other activities including the publication of journals newsletters and websites, as approved by the Executive Committee.

    Prof Lise Korsten and Prof Brenda Wingfield

    Story by: Martie Meyer, UP News and Events, October 2013

  • ACGT, UP and CBIO hosts national Galaxy (NGS data analysis) workshop

    5th Nov 2013

    The ACGT in collaboration with the UP IRT for Genomics and CBIO (UCT) hosted two Galaxy and NGS workshops in October 2013. The Pretoria event was held at the Bioinformatics and Computational Biology Unit at UP from the 14th -18th October. The Cape Town leg was hosted by CBIO (UCT) from the 21st-25thOctober.

    A total of 57 delegates were trained in total at both events (25 in Pretoria and 32 in Cape Town).  Applicants were rigorously screened based on the relevance and impact of the course on their current research. Attendance at the Pretoria event was representative of all five ACGT partner institutions. In addition delegates were also selected from UNISA and the National Zoological Gardens.

    The five day hands on workshop was presented by Mr David Clements, who is part of the Galaxy development team (Oregon, USA).  He was assisted by Prof Fourie Joubert (Pretoria) and Mr Gerrit Botha (Cape Town) who presented the SNP and variant analysis tutorial. Topics included RNA Seq, NGS data quality control, SNP and variant analysis, ChIP Seq, genome assembly, customizing Galaxy and installing Galaxy on Amazon web services.

    Participants at both the Pretoria and Cape Town events found the course to be relevant to their research and well presented. The outstanding presentations and active attention and participation of the delegates were major factors in the events success.

    The workshops presented forms part of a series of bioinformatics training courses hosted by ACGT and its partners to address specific needs in bioinformatics skills training. For more information on upcoming bioinformatics training events, visit the events page on the ACGT website or like us on Facebook.

  • Two UP professors elected to International Society for Plant Pathology

    4th Nov 2013

     

    At the recent International Society for Plant Pathology (ISPP) meeting in Beijing it was announced that two South Africans (both from the University of Pretoria’s Faculty of Natural and Agricultural Sciences), Prof Brenda Wingfield and Prof Lise Korsten were elected to the ISPP Executive Committee. Their term of office is from 2013 until 2018.

    Prof Wingfield was elected as the Secretary General while Prof Korsten as the Global Food Security Task Force Chair of the ISPP. The International Society for Plant Pathology promotes the world-wide development of plant pathology and the dissemination of knowledge about plant diseases and plant health management.

    The Society also sponsors the International Congress of Plant Pathology (ICPP) at regular intervals and other international meetings on plant pathology and closely related subjects. The Society establishes committees to consider and report on special fields or problems in plant pathology. The Society organises other activities including the publication of journals newsletters and websites, as approved by the Executive Committee.

    Story by: Martie Meyer, UP News and Events, October 2013

  • South African scientists show ‘gene-kissing’ impacts gene activation

    29th Oct 2013

     

    In a ground-breaking discovery that will have a major impact on our understanding of the regulation and function of our genes and DNA – our genetic blueprint – a group of scientists in South Africa is the first to show that when genes interact in three dimensions, or engage in so-called ‘gene kissing’, this has a major impact on how genes are switched on inside the cell. This landmark finding appears in the 24 October 2013 issue of the journal Cell, one of the world’s most prestigious research publications.

    This is only the fifth South African-affiliated article that has ever been published in Cell, and one of just two articles in three decades to feature an all-South African-based cast.

    A long-standing question in biology is whether ‘gene kissing’ is a cause – or simply correlated – with gene activation. This question was finally answered when a team led by Dr Musa Mhlanga, CSIR gene expression and biophysics research group leader, together with a collaborator at the University of the Witwatersrand faculty of Health Sciences, performed ground-breaking experiments to show that ‘gene kissing’ can switch genes on. The discovery sheds light on how genes change from inactive to active states, and how different genes can coordinate their activity simultaneously.

    Within each of our cells lies an incredible 1.2 metres of tightly coiled DNA, shrunk to a size one fiftieth that of a grain of sand. These genes encode our physical traits, such as eye colour or blood type. However, DNA also codes for genes that function constantly to keep us alive. These need to be switched ‘on’ and ‘off’ by the cell as needed. How gene activity is regulated has been the subject of intense study for many years, and scientists have suspected for some time that the physical contact between genes, or ‘gene kissing’ could play a role.

    “DNA is coiled and tangled like spaghetti inside the cell,” explains Prof Marc Weinberg from the University of the Witwatersrand and co-author of the study. “So, there are many places where the DNA touches and intersects. These interactions could be crucial to how the information in the DNA is read and interpreted by the cell, but this had never been shown before.”

    State-of-the-art microscopes, which were custom-built in South Africa by Dr Mhlanga’s group, were an important tool in being able to achieve single-molecule resolution in imaging this gene activity by peering deep into the nucleus of cells. These tools enabled them to see the activity of even a single gene, among the 30 000 human genes. Then, using DNA nucleases – nicknamed ‘molecular scissors’ – they were able to cut DNA at precise locations to prevent genes from making contact.

    According to lead author and Claude Leon postdoctoral fellow, Dr Stephanie Fanucchi, “being able to alter the genetic code in this manner is the ‘holy grail’ of molecular biology, but has only recently been made possible”. In this way, some genes were shown to ‘kiss’ in order to be switched ‘on’ and surprisingly in this instance, one gene acts as a master gene to orchestrate the activity of other genes. Co-author and Claude Leon postdoctoral fellow, Dr Youtaro Shibayama, remarks, “We jumped on the technology of producing efficient ‘molecular scissors’ as soon as it became available last year, and our integrated expertise in microscopy and molecular biology, combined with creative thinking, gave us a unique advantage over our peers in conducting this study.”

    The group is focusing some of its efforts on what this work could mean for human health. In late 2011, Dr Mhlanga’s laboratory at the CSIR was the first in Africa to generate induced pluripotent stem cells, a type of stem cells which could hold the key to growing new tissue to replace that which is diseased – and can even be used to create disease models ‘in a dish’. This occurred several years after the initial breakthrough in this respect in Japan. Combined with the knowledge to alter the genetic code and control gene activity, exciting novel experiments and therapeutic avenues can be envisaged for the future. Scientists will gain a deeper understanding of cancer, chronic diseases such as diabetes, allergy responses and a host of other diseases and important cellular processes. This important research, which has now been published, gives scientists across the globe new knowledge and tools about how genes behave and how to direct them, paving the way for future discoveries.

    Senior author, Dr Mhlanga, is passionate about what this discovery means, globally and to South Africa: “This work germinated from a desire to answer a fundamental long-standing question in gene regulation. Our goal is that scientists in Africa should not simply be consumers of fundamental scientific discoveries; rather they should be active contributors and producers to this body of basic scientific knowledge. We would like to train the next generation of scientists in Africa to become excellent scientists who routinely produce ground-breaking work. In this endeavour, we are very grateful for the continued support we receive from the Department of Science and Technology Emerging Research Area programme for several aspects of this work over the last few years.”

    The Minister of Science and Technology, Mr Derek Hanekom says this achievement makes the country proud.

    “We are proud of this achievement made through the pioneering research of the CSIR and its partners. We are confident that this important finding will shed light on and give scientists and researchers greater understanding of the treatment of a number of diseases, as well as insight into important cellular processes,” says Hanekom.

    The paper is titled, Chromosomal Contact Permits Transcription between Coregulated Genes, and is authored by Stephanie Fanucchi, Youtaro Shibayama, Shaun Burd, Marc S Weinberg, and Musa M Mhlanga.

    Story by: T. Tsedu, CSIR media release, October 2013

  • Researchers unite to stop malaria transmission

    28th Oct 2013

     

    Experts at the CSIR and the universities of Pretoria (UP) and Witwatersrand (Wits) are pooling their skills in a new project to find compounds for drugs that can block malaria transmission between humans and mosquitoes.

    Malaria is preventable and treatable. Yet, it infects millions and kills hundreds of thousands of people every year, while increasing drug resistance might soon limit our treatment options. Researchers have realised that, if they want to eradicate this disease, they need to look beyond treatment to drugs to block transmission between humans and mosquitoes.

    Dr Dalu Mancama, who heads the CSIRs biomedical technologies research group, says the aim of the Gauteng Gametocyte Consortium is to focus on specific stages in the life cycle of Plasmodium falciparum, the malaria-causing parasite which is transmitted from mosquitoes to people and vice versa.

    The parasite has a complicated lifecycle. When a mosquito bites, the parasite is passed into the human and develops in the liver for some weeks. Initially there are no symptoms to indicate that the person has been infected. The parasite is then released into the blood stream where it multiplies quickly and the symptoms of malaria become obvious, hydroxyzine belongs to the class of medications called antihistamines. it is used to relieve itching and other symptoms caused by allergic conditions.says Mancama.

    These parasites are called gametocytes when they are circulating in the blood stream at their sexual reproductive stage, ready to be picked up by the Anopheles mosquito when the infected person is once again bitten. They then reproduce in the mosquito and the life cycle of new parasites commences.

    The consortium has established local capacity to test,  in advanced infection models, compounds which researchers hope could disrupt the parasites life cycle and block transmission in future. Over the next two years they will test thousands of compounds provided by local South African researchers as well as libraries of compounds obtained from pharmaceutical companies.

    We have developed a model in vitro which allows us to rapidly identify drugs that have the most potential for further development. The idea is to develop drugs that work on different metabolic or biological processes in the gametocyte, to minimise the potential for future drug resistance.

    In South East Asia there is already resistance to artemisinin-combination therapy, the newest and now standard anti-malarial drug on the market, and the fear is that this resistance can spread.

    There are several stages during drug development. During the early development stage, researchers get rapid baseline information about the viability of a compound. The consortium has established a knowledge base in Gauteng consisting of molecular biologists, entomologists, analysts, chemists, biochemists and laboratory infrastructure.

    In future, instead of referring parts of the testing to different countries, much of this can be done locally in Gauteng. We grow the parasites in flasks and once they reach the stage of maturity needed for testing, we split them into 96-well plates and expose the parasites to the different compounds. We then add various reagents to allow us to establish whether the parasites have survived the exposure or not, Mancama explains.

    For the gametocyte stage, we use dyes which mimic a substrate which is normally found in parasites. After administering the drug, we expose the gametocytes to the dye. The parasites take it up and process it as if it were a normal endogenous substrate. During the processing, the gametocytes produce a metabolite which we can pick up fluorescently. The metabolite fluoresces at a certain wavelength.

    Higher florescence indicates higher parasite activity and vice versa. It is a way to figure out if the parasite is alive or dead.

    The group will also collaborate with researchers who look at other life stages of the parasite, for example when it develops in the mosquito just before being transmitted to humans.

    The consortium is funded by the Medical Research Council and the Medicines for Malaria Venture (MMV). The latter focuses on developing and delivering new drugs against malaria.

    Mancama says the researchers have done preliminary work and the testing of compounds is about to start. He leads the project along with Prof Lyn-Marie Birkholtz from UP and Prof Theresa Coetzer from Wits who specialise in gametocyte biology and advanced assays. They work in close collaboration with researchers at the NICD, and various leading groups and organisations abroad.

    According to the World Health Organization an estimated 219 million malaria cases occurred globally in 2010. The disease killed about 660 000 people, most of them children under five years of age.

    Story by: D. Mancama, CSIR News, October 2013