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  • Building Local Capacity for the Next Agricultural Revolution

    8th Apr 2021

    The ACGT hosted a webinar for the plant phenomics community on the 4th of March 2021. The webinar was designed as a feedback session for the Wageningen University and Research (WUR) “Drones for Agriculture” online course, as well as to discuss the progress made on formation of the SA Phenomics Society and exploring collaborative funding opportunities.

    The “Drones for Agriculture” course was attended by 20 participants (fully funded by the ACGT) associated with the University of Pretoria (UP), the Agricultural Research Council (ARC) and the South African Sugarcane Research Institute (SASRI).  The course was a self-paced, three-week online course facilitated by WUR’s top professors from the ‘Information Technology Group’ and the ‘Laboratory of Geo-Information Science and Remote Sensing Group’. The course was ran through the edX platform. Three participants gave feedback on the course, including Mr Phinda Magagula (UP), Dr Tingmin Yu (ARC) and Ms Natalie Hoffman (SASRI). They gave an overview of the course and also shared their highlights from the course. The participants shared how each institution hopes to implement the drone technology in advancing the plant phenotyping in their institutions. The presentations from the participants can be accessed at the link below.

    Dr John Becker from the ACGT chaired the sessions on the SA Phenomics Society formation and exploring collaborative funding opportunities for the community.  It was highlighted that since the first Plant Phenotyping and Precision Agriculture meeting held in 2019, a Charter for the SA Phenomics Society was developed and has been circulated to a number of institutions for approval. More institutions were identified at this meeting and the Charter has been circulated to them.

    In the last session of the webinar, the attendees were informed about the High-End Infrastructure grant application that will be submitted to the Department of Science and Innovation at the end of April 2021. This application is a collaborative effort by the ACGT, UP, the ARC and Stellenbosch University, from which national researchers stand to benefit. The community will be kept informed about the grant application progress.

    From the discussions it was highlighted the ”Drones for Agriculture” course was useful for the community. The ACGT will thus investigate whether there is enough interest to fund more participants for the course in 2021. The ACGT will also look at identifying other courses that might be beneficial for the community. The ACGT was also tasked with establishing an online discussion forum, which has been completed in the interim. This discussion forum includes participants from UP, ARC, CSIR, SASRI and Stellenbosch University. This discussion forum will be utilized by the community as a communication tool (sharing ideas, seeking assistance, etc.) around any topic within the plant phenotyping field. The community highlighted the need for a large data storage facility. The ACGT volunteered to explore data storage platforms that the community could utilize.



    Mr P Magagula – University of Pretoria

    Dr T Yu – Agricultural Research Council

    Ms N Hoffman – South African Sugarcane Research Institute

    Story by: the ACGT

  • More precise diagnoses made possible with whole genome sequencing

    17th Mar 2021

    More than 1,200 people with rare diseases have received a diagnosis thanks to the integration of large-scale genomics into the Stockholm region’s healthcare system. This is according to a study from Karolinska Institutet in Sweden that analyzed the result of the first five years of collaboration on whole genome sequencing between Karolinska University Hospital and SciLifeLab. The work, published in Genome Medicine, constitutes a major leap forward in the emerging field of precision medicine.

    “We’ve established a way of working where hospital and university collaborate on sequencing each patients’ entire genome in order to find genetic explanations for different diseases,” says the paper’s first author Henrik Stranneheim, researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet. “This is an example of how precision medicine can be used to make diagnoses and tailor treatments to individual patients.”

    Large-scale whole genome sequencing technology, that is the process of determining an individual’s complete set of genetic material, has made rapid advances over the recent decade. Despite this, few clinics worldwide routinely use it to diagnose patients…

    Please use the following link to access the rest of the article: ScienceX


  • University of Pretoria researchers receive prestigious grants for cutting-edge cancer research

    17th Mar 2021

    Two University of Pretoria (UP) researchers are among nine researchers in South Africa who have received funding grants from the South African Medical Research Council (SAMRC) as part of the Strategic Health Innovation Partnerships (SHIP) programme. The grants are worth approximately R3 million each and are to be used over a three-year period.

    Professor Robert Millar and Dr Iman van den Bout, academics and researchers of the Centre for Neuroendocrinology in UP’s Faculty of Health Sciences, have received funding to support their research into cutting-edge solutions for the diagnosis and treatment of prostate cancer and breast cancer respectively.

    Professor Tiaan de Jager, Dean of UP’s Faculty of Health Sciences, said he is delighted that two researchers from the Faculty are part of producing such important work. “At the Faculty of Health Sciences, we pride ourselves on using our research to solve today’s pressing issues in the communities we work and live in. Additionally, I am proud to hear that our Centre for Neuroendocrinology has received two grants of about R3 million each which will go into finding innovative and lasting solutions to the current challenges facing the diagnosis and treatment of cancer in SA.”

    The announcement was made today (8 Feb) at a virtual ceremony. The MRC SHIP is a partnership between the SAMRC and the Department of Science and Technology that funds and manages innovative projects focused on the development of new drugs, treatments, vaccines, medical devices and prevention strategies. This partnership provides life-saving innovations to the health industry and the South African public through involvement in developing new and improved treatment options

    An A-rated scientist with over 450 peer review publications, Prof Millar will continue his lifelong work by using the grant to test a new way to diagnose and stratify prostate cancer among South Africans, using a ‘liquid biopsy’ to improve outcomes.

    “In South Africa, the age-standardised prostate mortality rate is one of the highest in the world. There is currently no systematic prostate cancer screening program in South Africa within the state-run healthcare system,” Professor Millar explained. “The standard diagnostic test for prostate cancer in South Africa consists of digital rectal examination and prostate specific antigen (PSA) and sometimes prostate biopsy. These tests are, however, characterised by high false-positive and false-negative values, leading to under- and over-diagnosis and consequent harm to patients, and increased costs to the healthcare system. My aim is to show that by utilising the novel state-of-the-art non-invasive genomic technology quantifying tumour mRNA in blood, PROSTATest and NETest, in South African black men, we can improve diagnosis and treatment selection and reduce costs to the healthcare system. Importantly, these tests have demonstrated the potential to identify new therapies for advanced prostate cancers which are not responsive to the major treatment –  androgen deprivation therapy – thus addressing the SHIP call for a ‘pharmacogenomics approach to failed therapies.’”

    For Dr van den Bout this project forms part of work that began 20 years ago. He will use his grant to initiate and develop the first breast cancer organoid biobank, which will be used to develop better prediction tools for South African women’s response to standard chemotherapy regimens offered in the public health system.

    “As I keep developing the project, I feel very strongly that this project will establish a resource and knowledge base that will be of immense value to local cancer scientists in their quest to improve breast cancer patient care in our country,” Dr van den Bout said. “It is already known that a significant percentage of African breast cancer patients that are treated with the standard chemotherapies available in the public health system fail to respond well. In this study we seek to develop a way to test living cells from the tumours of these patients for their reaction to the therapies in the lab, and to see if this will predict how the patient will respond to the treatment. Eventually, we hope that our research will lead to clinical tools with which we can assess each incoming breast cancer patient to determine what therapies will be most effective for them.”

    Professor Tawana Kupe, UP Vice-Chancellor and Principal, said the two researchers embody UP’s vision of being the leading research-intensive university on the African continent. “Cancer in South Africa and on the African continent remains one of the most devastating diseases. I am proud that two of our researchers are leading the quest to find lasting and more effective solutions in the diagnosis and treatment of breast cancer and prostate cancer. It proves that at UP, we are committed to producing research that is relevant, innovative and that will improve the lives of ordinary people across Africa and the world.”

    Story by: Masego Panyane, for the University of Pretoria 

  • “Silent” Mutation Linked to Worse Kidney Cancer Outcome

    “Silent” Mutation Linked to Worse Kidney Cancer Outcome
    19th Feb 2021

    For decades, researchers have viewed synonymous mutations as inconsequential quirks of the genome. Due to the way the genetic code is set up—where multiple three-base-pair codons can encode the same amino acid—mutations can arise that don’t change a protein’s amino acid sequence. Scientists have largely dismissed these anomalies as harmless oddities.

    But like other historically underappreciated aspects of the genome, scientists are realizing that many “silent” mutations might not be so silent after all. Research suggests they’re often subject to selective pressure and could play a role in cancer, autism, and schizophrenia.

    A study published online last week (February 12) in iScience adds to the mounting evidence that synonymous variants can have consequences. The authors describe a synonymous mutation in the gene BAP1 that was associated with a worse-than-expected prognosis in a kidney cancer patient. Their subsequent experiments suggest that the mutation has this effect by disrupting cells’ RNA splicing process, by which freshly transcribed messenger RNA (mRNA) is converted into digestible fragments ready to be translated into protein. Because the cancer patient lacked a second healthy copy of the gene, the silent mutation may have resulted in a complete loss of function of BAP1.

    “To my knowledge, tying a specific synonymous mutation [to] a clinical outcome [in cancer] is a novelty,” remarks Fran Supek, a cancer geneticist at the Institute for Research and Biomedicine in Barcelona who wasn’t involved in the study. “I’m always glad to see that researchers are thinking a bit outside the box . . . and looking at understudied classes of genetic changes that may help us solve a certain number of patients with genetic diseases or with cancer.”

    While combing through The Cancer Genome Atlas(TCGA)—a public database of genomic samples from more than 11,000 patients around the world—Samuel Peña-Llopis and his colleagues discovered an entry from a patient with an unusual course of disease. The 73-year-old Caucasian woman had clear-cell renal cell carcinoma, the most common form of kidney cancer, with a mutation in PBRM1, a gene involved in chromatin remodeling.

    Although PBRM1 mutations are normally associated with relatively good clinical outcomes in such patients—with a median survival of 117 months, according to TCGA data—the patient died only 56 months after diagnosis, says Peña-Llopis, a cancer geneticist specializing in kidney cancer and uveal melanoma with the German Cancer Consortium at the University Hospital Essen in Germany.

    The team noticed that she also had a synonymous mutation in BAP1, which encodes an enzyme involved in regulating the degradation of proteins. The mutation changes a thymine to a guanine, which still results in the same amino acid, glycine, encoded both by GGT and GGG. Curiously, the patient also had very low abundance of BAP1 protein, in fact, it was on par with renal cell carcinoma patients who have nonsynonymous loss-of-function mutations in BAP1, which tend to be linked to severe outcomes. The team suspected that the silent BAP1 mutation might somehow affect the gene’s transformation into protein.

    The path by which DNA turns into protein is a long and winding one. First, double-stranded DNA is teased apart and the strands are individually transcribed into single strings of pre-mRNA, a rough draft of the instructions needed to turn it into protein. Then it must be spliced, whereby various proteins bind to different sites across the pre-mRNA and cut out noncoding nucleotide sequences—introns—and fuse the coding parts—exons—together. Only then is the mRNA ready for other cellular machinists to translate it into protein.

    One way by which synonymous mutations can perturb this process, previous research suggested, is by altering the specific binding sites of RNA splicing proteins, which are required to properly integrate different exons. If they can’t bind—or the altered codon causes the wrong proteins to bind—they might end up skipping over important bits of genetic code—called “exon skipping”—which can result in a dysfunctional protein. Because the synonymous mutation located in BAP1’s exon 11 was close to a splice site critical for joining this exon to the next, “we thought that maybe the splicing system was affected,” Peña-Llopis recalls.

    To find out, the team conducted a series of experiments with genetic constructs containing BAP1’s exon 11, into which they had inserted fluorescent proteins. They expressed the construct in a human cancer cell line. Based on the color that emerged under a microscope, they could tell if the exon was being integrated or skipped. They observed nearly 100 percent skipping when the construct contained the synonymous mutation, significantly more than when using the construct based on the unmutated version of BAP1.

    If exon 11 is skipped, that likely causes a loss of BAP1 for that gene copy, Peña-Llopis explains. Because that exon has 185 base pairs—which is not a multiple of three—losing it will cause a shift of the three-base-pair reading frame that enzymes use for protein translation. That, in turn, would cause a codon further down the line to be misread as a stop codon, signaling the protein translation machinery to terminate. mRNA transcripts containing premature stop codons are typically degraded by the cell. In this particular patient, this likely led to a complete loss of BAP1 because she had lost her second copy due to a deletion of a small chromosome segment, which is common in that cancer subtype.

    Synonymous mutations in kidney cancer patients

    Back in the TCGA database, which includes nearly 500 clear-cell renal cell carcinoma patients, the team found another eight patients who had synonymous mutations in BAP1 exons near sites important for splicing, two of which were located inside the sites necessary for gluing exons 10 and 11 together. Considering that there are 32 splicing sites across the 17 exons that make up BAP1, finding two out of eight is a significant number, Peña-Llopis says, “suggesting that this is a hotspot for inactivation of BAP1.” However, the two patients had very different clinical outcomes, suggesting that other genetic alterations also play a role in the prognosis.

    “I think this is an important finding,” remarks James Brugarolas, a physician-scientist and oncologist who directs the kidney cancer program at the University of Texas Medical Center. BAP1 is mutated in around 10–15 percent of all clear-cell renal cell carcinomas, mostly through nonsynonymous alterations. “The study provides relatively convincing evidence that . . . mutations that do not affect the protein sequence in BAP1could be pathogenic driver mutations, leading to the inactivation of the tumor suppressor protein,” adds Brugarolas, who has collaborated with Peña-Llopis in the past but wasn’t involved in the new research.

    Brugarolas says that the data would have been even more convincing had there been more RNA sequencing and immunohistochemistry data from the patients’ tumor available, which could yield more definitive evidence of exon skipping. And, of course, such findings can always be better supported by larger sample sizes and replication in independent datasets, Supek adds. That said, “I think the in vitro experiments that they [did] suggest that the mutation they’ve identified has the potential to alter splicing. And clearly, exon 11 escaping would result in a nonfunctional protein due to a premature stop codon. One could make a very convincing argument for that,” Brugarolas says.

    The clinical relevance of the finding is not yet apparent. Targeting loss-of-function mutations in tumor suppressor genes such as BAP1 has lagged behind targeting gain-of-function mutations, for instance, in enzymes that control cell growth and function, Brugarolas says; it’s generally easier to inhibit misfit proteins than to correct something that has been already abolished by mutation. It’s also unclear if BAP1 mutations could be used as biomarkers to predict patients’ responsiveness to therapies. “How mutations in BAP1[should] be leveraged for therapy remains unknown,” Brugarolas adds.

    On the whole, the findings indicate that researchers should be paying more attention to synonymous mutations, notes Thomas Mitchell, a clinician-scientist focusing on kidney cancer at the Wellcome Sanger Institute in the UK. “[There is] little awareness of synonymous mutations and their role in cancer. In general, they are ignored in sequencing studies as it has been felt that they are very unlikely to be drivers.”

    Nevertheless, larger studies in the past have predicted that synonymous mutations could have pathogenic effects. In 2014, Supek and colleagues estimated that around 6–8 percent of pathogenic single-nucleotide mutations in cancer genes are synonymous mutations. Taken together with other studies, research seems to converge on an estimate of 5 percent of all driver mutations being synonymous mutations—a “non-negligible amount” that may be quite significant for some individual cancer patients, Supek says. Exon skipping is one mechanism by which such mutations could have deleterious effects, “but it’s probably going to be different for every synonymous mutation.”

    Understanding silent mutations, along with other overlooked genetic alterations, could help unlock the underlying causes of disease for many individual patients for whom mutations don’t clearly fall into the nonsynonymous bucket, and open the door to finding treatments. “The human genome is a very complex thing, and there are many ways in which it can break and result in disease,” Supek says.

    J. Niersch et al., “A BAP1 synonymous mutation results in exon skipping, loss of function and worse patient prognosis,” iScience, doi:10.1016/j.isci.2021.102173.

    Story by: Kararina Zimmer, for The Scientist

  • Another Potentially Immunity-Evading SARS-CoV-2 Variant Detected

    Another Potentially Immunity-Evading SARS-CoV-2 Variant Detected
    19th Feb 2021

    Researchers in the UK have identified a new SARS-CoV-2 variant with mutations that could allow it to evade immunity-conferring neutralizing antibodies.

    Known as B.1.525, the variant was first detected in the UK and Nigeria in December. It’s since been found in 11 other countries, including Denmark, the US, and Australia.

    B.1.525 sports a handful of mutations, including one on the spike protein called E484K. This mutation is also found in variants that emerged in South Africa and Brazil and seems to help the virus evade antibodies, The Guardian reports. In addition, B.1.525 has similarities to the highly transmissible B.1.1.7 variant that also emerged in the UK.

    “We don’t yet know how well this [new] variant will spread, but if it is successful it can be presumed that immunity from any vaccine or previous infection will be blunted,” Simon Clarke, an associate professor of cellular microbiology at the University of Reading in the UK, tells The Guardian.

    Moderna and Pfizer are already working to develop booster shots to give vaccines an edge against the slew of new virus variants. The good news is that because many of the variants share the same mutations, new vaccine versions are likely to confer immunity to multiple versions, according to The Guardian. “This [E484K] change seems to be the key change at the moment to allow escape, so that’s the one you put into the tweaked vaccine,” Jonathan Stoye, a group leader at the Francis Crick Institute, tells the news outlet.

    Story by: Asher Jones, for The Scientist

  • UP researcher’s team discovers new compounds with the potential to eliminate malaria

    28th Jan 2021

    The University of Pretoria (UP) has discovered new potent chemical compounds that show potential as candidates for both the treatment and elimination of malaria.

    Professor Lyn-Marie Birkholtz, Professor in Biochemistry and South African Research Chair in Sustainable Malaria Control (part of the South African Research Chair Initiative, SARChI), was part of an international team that published this discovery in the journal Nature Communications on 11 January. “The breakthrough involves the identification of unique compounds that are able to kill several stages of the malaria-causing parasite and can block the transmission of the parasite between humans and mosquitoes,” she explained.

    The deadly human malaria parasite Plasmodium falciparum occurs in South Africa. These parasites are transmitted to humans by female Anopheles mosquitoes. The only means of killing the parasite itself is to use chemical drugs, but new antimalarial drugs are urgently needed to address the growing concern of antimalarial drug resistance.

    Prof Birkholtz describes the parasite as a “shape shifter” since it can take on multiple forms while in humans. Some of the forms cause disease and others allow the parasite to be transmitted back to mosquitoes to continue the life cycle. Prof Birkholtz states: “To eliminate malaria, it is essential that we have the necessary tools to kill all these different forms of the parasite. We can then cure patients of the disease but, importantly, also block the malaria transmission cycle. This is the only way to achieve malaria elimination.

    South Africa is leading regional malaria elimination efforts as part of four frontline countries in southern Africa including Namibia, Botswana and Eswatini.

    In an innovative strategy, the team looked for new chemical compounds that can do exactly this, but that are completely new so that the parasite does not have resistance against them. The team runs a unique research platform on the African continent, in which all of these stages of the malaria parasite can be produced in the lab and be used to test chemical compounds. The team discovered compounds that kill the disease-causing form and compounds that blocked the parasite from infecting mosquitoes in the lab.

    Two potent compounds target processes essential to the parasite’s survival: one is a clinical candidate against tuberculosis and blocks cell membrane synthesis and another is an anti-cancer candidate that targets epigenetic mechanisms (mechanisms that control cell fate beyond the genome). “This is the first time that these compounds were shown to have activity against malaria parasites and since they are not toxic to humans, they show the potential to be developed as antimalarials for both the treatment and elimination of the disease,” said Prof Birkholtz.

    The discovery was made possible by the team’s use of an open-source chemical compound set called the Pandemic Response Box, developed by the Switzerland-based Medicines for Malaria Venture (MMV) and the Drugs for Neglected Diseases Initiative (DNDi). This compound box contains compounds that can be used for drug repurposing/repositioning, a process where drugs that have activity against a specific disease (e.g. cancer) can be reused for another disease (e.g. malaria). Dr James Duffy, MMV Project Director, describes the discovery “as an important breakthrough that emphasises the potential to use existing drugs as inspiration for drug discovery projects targeting different diseases. Never before has this been more important than in light of current outbreaks, where the rapid response to discover new chemicals able to kill infectious organisms is essential.”

    Prof Birkholtz directs the parasite cluster of the UP Institute for Sustainable Malaria Control (ISMC), a multidisciplinary institute with a focus on integrated innovations towards malaria elimination in South Africa. Professor Tiaan de Jager, Director of the ISMC and Dean of Health Sciences at UP, said: “A discovery of this kind attests to the leading expertise in antimalarial drug discovery at UP, and in South Africa, addressing African-centred societal challenges. This work also shows the commitment of scientists at UP to contribute to the United Nation’s Sustainable Development Goal for Good Health and Wellbeing.”

    Prof Birkholtz’s team led the transmission-blocking drug discovery effort as partner in the South African Malaria Drug Discovery Consortium (SAMDD) that includes two other South African Research Chairs, Professor Kelly Chibale (Chair in Drug Discovery at the Drug Discovery and Development Centre, H3D, at the University of Cape Town) and Professor Lizette Koekemoer (Chair in Medical Entomology at the WITS Institute for Research on Malaria at the University of the Witwatersrand) as well as scientists from the Council for Scientific and Industrial Research and international partners from the USA and Spain. The work has benefitted from sustained funding from the MMV and the Medical Research Council’s Strategic Health Innovation Programme (SHIP) and affirms that investments in health innovations places South Africa at the forefront of discovery.

    Story by: The University of Pretoria 

  • What’s Ahead for SARS-CoV-2 Research in 2021

    15th Jan 2021

    Ever since the virus now known as SARS-CoV-2 was first identified and sequenced by researchers in China a year ago, a tidal wave of research on the pathogen and its associated disease, COVID-19, has swamped the scientific literature. Indeed, an analysis posted as a preprint last month found that more than 84,000 papers related to COVID-19 were published in the first 11 months of 2020.

    Even given that output and the recent rollout of vaccines against the disease, researchers who study the virus aren’t ready to put it on ice and move on to other problems. Here are some of the key areas where we’re likely to see advances in understanding this year.

    Where did it come from?

    Teasing out SARS-CoV-2’s origin is important, says disease ecologist Jonathan Epstein of EcoHealth Alliance, because knowing how the virus got into humans could yield clues about how to avoid future spillovers. The SARS outbreaks of 2003 and 2004 spurred research (of which Epstein was a part) that identified horseshoe bats as a reservoir for this family of coronaviruses, he notes, but it’s still not known exactly how either virus made it from bats to people. Understanding whether SARS-CoV-2 jumped directly from bats into people, or whether it first infected a wild or domesticated intermediary species, would help in pinpointing particular human activities that could be putting us at risk of future zoonotic events, he says.

    The World Health Organization (WHO) has convenened a team to investigate the virus’s origins that began traveling to China early this month, WHO head Tedros Adhanom Ghebreyesus said in a January 5 briefing. According to WHO spokesperson Tarik Jašarević, the team’s plans include reviewing hospital records from late 2019 to identify illnesses that might have been COVID-19, interviewing people who were the first known cases, and finding out what animals were traded at a market in Wuhan associated with some early infections, and possibly other local markets around the time of the outbreak, and where those animals came from. Jašarević did not say when the team’s findings might be made available.

    In addition to prevention, another benefit of knowing the animal origins of coronaviruses is the opportunity to design medicines against them in advance, namely, “broadly neutralizing antibodies that can hit not just SARS-2, but other related coronaviruses that we know are in animal reservoirs,” says virologist Kartik Chandran of Albert Einstein College of Medicine in New York. That’s a long-term goal of his current work on identifying effective antibodies that can be used as a COVID-19 drug. And, he says, it will also be important to figure out how to develop vaccines that confer protection against a broad swath of such coronaviruses. “From a research standpoint, in the next few years, that’s going to be a major challenge.”

    More treatment options

    Even with effective vaccines, humanity is likely stuck with SARS-CoV-2, much like the cold-causing coronaviruses and influenza, Chandran says. That means there’s an ongoing need for effective treatments for the disease. One issue with current monoclonal antibody treatments, he notes, is that they require large volumes to be administered by IV, creating logistical challenges. “If we can get these things to be potent enough, we ideally would be able to give them by intramuscular injection, rather than giving them IV—that would make a huge difference,” he says. “But that’s going to require a jump in potency that’s quite significant.”

    So far, one standalone monoclonal antibody, bamlanivimab, and a combination of two, casirivimab and imdevimab, have received emergency use authorization from the US Food and Drug Administration (FDA). Both treatments were tested in clinical trials on people with mild or moderate disease, and the studies found that those who received them had about one-third the risk of visiting the ER or being hospitalized in the following four weeks compared with patients who got a placebo. Other currently available treatments include the antiviral remdesivir and the steroid dexamethasone, each of which are used for some hospitalized patients, and convalescent plasma, which, according to a small trial published this week, halved the risk of severe respiratory illness when given within three days of the onset of symptoms.

    “We were encouraged to see the quick pace of development of the monoclonal antibodies,” says Esther Krofah, the executive director of the FasterCures center at the nonprofit Milken Institute. “But I think there’s still a lot more to be done, particularly in an outpatient setting.” In particular, a small-molecule drug that could be taken by patients at home to reduce their chances of hospitalization would alleviate some of the pressure on the healthcare system. One such drug she’s keeping an eye on, camostat mesilate, is a protease inhibitor currently being tested in multiple clinical trials.

    FasterCures is tracking more than 300 prospective vaccines and treatments for COVID-19 that are in various stages of development. Krofah says she expects many current clinical trials not to yield conclusive results due to poor design or problems recruiting enough patients. One promising tack, she says, are the so-called master protocol studies that compare different treatments both with each other and with a placebo.

    A series of such trials sponsored by the National Institutes of Health, for example, several of which are expected to be completed later this year, are testing immune modulators, monoclonal antibodies, and blood thinners in groups of COVID-19 patients. In other trials, some repurposed antibiotics and an antifungal have also shown promise and could make it to the clinic this year, says Yasmeen Long, also of FasterCures.

    Variant surveillance

    As SARS-CoV-2 continues to mutate, researchers will need to determine whether available vaccines are effective against newer variants, Chandran says, such as the B.1.1.7 and 501.V2 variants that have drawn much attention in recent weeks. Akiko Iwasaki, an immunologist at Yale University, says that while current variants are “likely going to be covered by the existing vaccines, in the future, there may be new variants that can emerge that would evade the current vaccine”—meaning surveillance of viral variants should be a priority.

    To date, the US has sequenced 58,560 SARS-CoV-2 samples, compared to the UK’s 209,038, The New York Times reports, but a Centers for Disease Control and Prevention official tells CNN that the agency and its partners are working to double the number of viral sequences they post publicly each week to about 6,500.

    The long haul

    One of Iwasaki’s current projects is profiling the immune responses of people whose COVID-19 symptoms have lasted for months, a phenomenon known as long COVID. “Right now, there are thousands of people suffering from long COVID,” she says. “But there’s very little insight as to how the disease is caused and prolonged for so many people.”

    Understanding the mechanism of the disease could point the way to ways of treating it, she says, and might also shed light on other cases of chronic disease associated with an initial viral infection. In particular, after recently finding that hospitalized COVID-19 patients harbor distinct antibodies against their own proteins, known as autoantibodies, she and her colleagues have begun investigating whether such autoantibodies are at play in long COVID.


    Story by Shawna Williams, for The Scientist 

  • Repurposing viruses- from disease causing agents to therapeutic agents

    Repurposing viruses- from disease causing agents to therapeutic agents
    24th Nov 2020

    The ACGT hosted a webinar on “Nano-Engineering Gone Viral: Plant Virus-Based Therapies” presented by Prof Nicole Steinmetz from the University of California, San Diego. The webinar, held on the 3rd of November 2020, was part of the ACGT series of webinars introduced due to Covid-19 restricting physical meetings.

    Prof Nicole Steinmetz

    Prof Steinmetz’s interest in plant virus-based nanotechnology has been a lifelong academic interest of hers. She has been researching the field since her postgraduate years. The presentation took the audience on a journey of on how engineering plant viruses can be utilized for plant and human health. Prof Steinmetz highlighted that plant viruses (as a biologic material) offer high precision compared to synthetic systems which makes them an ideal therapeutic agent. The presentation then explored different applications of the technology which included molecular imaging to aid risk stratification, delivery of therapies, targeting plant health (pesticide delivery), and immunotherapy and vaccines.

    Prof Steinmetz stated that “plant virus-based technologies could be produced ‘in the region for the region’ in developing countries lacking a conventional refrigeration system and health infrastructure, toward low-cost and edible therapeutics.” The “region for the region” concept could be realised with institutions such as the CSIR, who are active in this field, and others in the country engaging in collaborative efforts with local and international researchers such as Prof Steinmetz to produce region specific plant-based technologies.

    The Centre has extended a research visit to Prof Steinmetz and are hopeful that she can visit the partnership as soon as travel restrictions allow.

    To view the full webinar, please click here.

    Story by: the ACGT

  • Unique Advantages of Top-Down Proteomics Showcased in Online Workshop

    Unique Advantages of Top-Down Proteomics Showcased in Online Workshop
    5th Nov 2020

    Prof David Tabb

    The ACGT hosted a webinar-based workshop on “Biological Research via Top-down Proteomics” on the 9th of October. The workshop was facilitated by bioanalyst Professor David Tabb from Stellenbosch University’s Division of Molecular Biology and Human Genetics.

    The workshop was another instalment of ACGT’s annual proteomics training workshops aimed at increasing capabilities in the field for South African researchers. Due to the pandemic, most of the Centre’s 2020 capacity building events had to be moved online, similar to international trends.

    Professor Tabb, who has been with Stellenbosch University since 2015, has contributed immensely towards increasing informatics analyses capabilities within the South African proteomics community. He has previously partnered with the ACGT on a number of training workshops, in conjunction with international and local proteomics experts.

    This advanced proteomics workshop described analytical chemistry advances that have made top-down proteomics research an area worth pursuing. The workshop also highlighted some research areas where top-down proteomics has been employed and proven to add valuable insights into complementary analyses, especially in the area of proteoforms.

    The workshop was attended by 49 proteomics researchers from across South Africa as well as scientists from other African countries.

    The workshop was aimed at stakeholders at various levels of laboratory and informatics analyses experience. It was also followed by a constructive question and answer session, where the need for collaboration in the country, as well as the need for utilizing a combination of proteomics technologies to address any particular biological question, were highlighted.

    Click here to access the workshop recording.

    Story by: The African Centre for Gene Technologies


  • Wits Professor wins top chemistry prize

    2nd Nov 2020

           Professor Charles de Koning

    Wits Professor of organic chemistry, Charles de Koning, recently won the South African Chemistry Institute’s (SACI) gold medal – the organisation’s top award. He was also inducted as a Fellow of SACI.

    For De Koning, however, the award came as a bit of a surprise – since he wasn’t online during the announcement. As with most events this year, the SACI AGM and prizegiving took place virtually. “I had been on calls all day and decided to go cycling after work. When at some point I checked my phone, I saw that I had multiple missed calls,” says De Koning about the moment that he had found out that he had won the institute’s top prize.

    The SACI only awards a single gold medal per year, to “a member of the Institute in good standing, whose scientific contributions in the field of chemistry or chemical technology are adjudged to be of outstanding merit”. De Koning has been involved with SACI since 1992 when he returned to South Africa after completing two post-doctoral stints abroad. He has served as treasurer for the SACI Gauteng branch and organised several conferences. The gold medal itself though is only one part of the award. De Koning will also deliver the gold medal plenary lecture at the next SACI symposium, and receive a cash prize.

    De Koning’s research focuses on organic synthesis – organic chemistry using simple building blocks. By combining these building blocks, and developing new synthetic methods, new compounds can be assembled that have unique properties. In particular, De Koning who has built up a research profile of 136 peer-evaluated publications, and six book chapters throughout his career, is interested in the application of these new resources to human health and medicine.

    In a high profile publication last year, De Koning and his team announced the discovery that cashew nut shells can be processed to extract building blocks for the manufacture of UV absorbent materials. Rather than focusing on dwindling petrochemical resources, De Koning’s team was able to source these building blocks from inedible waste products.

    “By utilising these methods, this research has the potential to reveal many valuable compounds from renewable sources in the world around us,” says De Koning.

    Beyond his research, De Koning considers his mentorship and supervision of students to be his greatest achievement – and the best part of the job. He has supervised a total of 36 PhD and 27 MSc students, many of whom have gone on to excel at careers in their own rights.

    Some of his previous students, Willem van Otterlo, Edwin Mmutlane and Darren Riley, are now academics in organic chemistry at the University of Cape Town, the University of Johannesburg, and the University of Pretoria respectively. De Koning has also fostered a collaborative spirit with colleagues at two German universities, the Johannes Gutenberg-Universität Mainz and the University of Cologne, with which he has managed a student exchange programme over the past few decades.

    De Koning’s interest in organic chemistry may have roots in his childhood – as a child he enjoyed playing with Lego.

    “Back in the day there were no kits to build cars or spaceships, you just got the box of Lego pieces and made what was in your imagination,” he says. This interest in building blocks as a child, combined with a passion for organic synthesis during his undergraduate degree led to his successful career in “molecular engineering” through organic chemistry. Intrigued by the concept, De Koning went on to pursue a Masters and PhD on the subject, subsequently travelling from Boston to Hawaii before landing back in South Africa.

    The SACI symposium at which De Koning will deliver his gold medal plenary lecture is set to take place in the Western Cape Province in 2021, although the dates may change given the current global Covid-19 pandemic.

    Story and image by: The University of the Witwatersrand