• To single cell RNA-sequencing data and beyond: a tale of a successful webinar

    17th Nov 2021

    Single-cell RNA sequencing can reveal complex and rare cell populations, uncover regulatory relationships between genes, and track the trajectories of distinct cell lineages in development. The African Centre for Gene Technologies (ACGT) and researchers from the University of Zurich decided to host a webinar titled “The differential analyses and beyond for single cell RNA-sequencing data” on 03 November 2021.

    In this webinar, Professor Mark Robinson shared his expertise in this field and demonstrated various strategies for differential analyses from multi-sample, multi-group single cell RNA-sequencing data. Prof Robinson’s research interests are in the application of statistical methods and data science to experimental data with biological applications within the context of genomics data types. Prof Robinson’s talk was followed by a presentation from Dr Simone Tiberi  who focused on key considerations on single cell RNA-sequencing data with specific focus on quality control and RNA velocities. Dr Tiberi has interests in the development of cutting-edge statistical methods in bioinformatics, mostly for bulk and single-cell RNA-seq data.

    The ACGT would like to credit the success of this event to the generosity of researchers from the Institute of Molecular Life Sciences at the University of Zurich in Switzerland; Professor Robinson and Dr Tiberi as well as Dr John Becker from the ACGT who chaired the session. The ACGT hopes that everyone who attended the webinar benefited in one way or another. This was not the first RNA-sequencing event organized by the ACGT and this group. A successful workshop was hosted in 2019.  Unfortunately, one could not be hosted in 2020 as we were all adjusting to the pandemic and lockdowns. The ACGT will explore other topics in RNA-seq technologies that could be beneficial to members in the ACGT partnership and those who are active in these areas.

    For more information, please contact Mr Molati Nonyane at or Tel: 012 420 6139.

     

  • The Second MSA Symposium exhibits South African talent in the field of Metabolomics

    16th Nov 2021

    The second Metabolomics (MSA) Symposium was held on the 20-21 October 2021. This was another installation of efforts by members of the MSA committee of directors, the MSA subcommittees, the African Centre for Gene Technologies (ACGT) and the many other partners. What started off an idea three years ago, has grown into a very useful coming together of researchers and students with a common interest. The symposium was a to demonstrate the Metabolomics work that has been taking place in South Africa and by some of the members of the association.

    The symposium was held over two days and attracted a crowd of over 100 participants. There were 24 speakers of diverse backgrounds and research experience. The event was especially designed to offer the younger speakers an opportunity to present their work and get some exposure. The sessions were chaired by Dr Aurelia Williams (North-West University), Dr Fidele Tugizimana (University of Johannesburg) and Prof Duncan Cromarty (University of Pretoria).

    Here are some highlights from the symposium:

    Keynote speakers included:

    • Prof Alvaro Viljoen from Tshwane University of Technology whose talk was titled Metabolomics – an indispensable tool in medicinal plant research.
    • Dr Tiffany Thomas from Columbia University Medical Center in the United States who presented on the structural and metabolic changes of red cells in hospitalized COVID-19 patients.
    • Dr Volker Kruft from SCIEX who gave a talk on Clinical Metabolomics: The path to finding new markers.

    Training sessions:

    • Molecular Networking by Dr Fidele Tugizimana and his young team from the University of Johannesburg.
    • Validation of Metabolomics Data by Dr Mari van Wyk from North-West University (Potchefstroom).

    The AGM

    The annual general meeting was held at the end of Day 1 and was used as an opportunity for MSA leadership to provide feedback of progress from the previous periods as well as insights into future MSA plans.

    Best Speaker Awards:

    • Anza T. Ramabulana from the University of Johannesburg was awarded the best speaker award for her talk titled Metabolomics and computational tools to characterize the chemical space of Momordica plant species.
    • Chanel Pretorius from the University of Johannesburg was the other best speaker for her talk titled Metabolomic analysis of oat (Avena sativa L.) plants: A strategy for cultivar identification and differentiation.

    The first MSA symposium was held not too long ago during the launch of MSA in 2019. This ACGT has been very invested in doing eve thing possible to facilitate the growth of MSA.  It is very encouraging that momentum from all previous efforts has not been lost and that the MSA and its initiative is still ongoing. We would like to thank the speakers for donating their time and the attendees for making time to attend this event. We would like to thank the sponsors of this event and we look forward to future to working with you again in future events.

     

  • The future of South African plant biotechnology research and innovation is bright!

    The future of South African plant biotechnology research and innovation is bright!
    5th Oct 2021

    Four highly promising emerging plant biotechnology researchers attracted a large audience to a webinar aimed at spotlighting the next generation of researchers in the field in South Africa. The event drew 94 registrants, indicative of the quality of research on display by the emerging PhD graduates.

    The webinar had diverse representation from all the ACGT partner research institutions. The presentations from the University partners (Johannesburg, Pretoria, and the Witwatersrand) centered around plant pathogens and how to curb their impact on economically important food crops, including viral, bacterial and fungal pathogens. The CSIR presented work on an engineered Agrobacterium repurposed to produce potent HIV antibodies in a tobacco production system.

    The webinar was led by Professor Chrissie Rey, a highly experienced viral researcher focusing on the African subsistence crop Cassava. Professor Rey and other partner researchers instilled the discussions with decades of research experience and constructive suggestions.

    The closing session focused on diversity in research and how the pandemic has affected the ability of scientists to network and gain viewpoints from different stakeholders. The speakers and audience agreed that a lot of collaborative opportunities existed in the South African biotechnology environment for further impact through combined critical mass. The ACGT will continue to find the synergies to move the research further along the development pipeline.

    Meet our speakers on the day:

    Dr Bulelani Sizani – (University of the Witwatersrand) a post-doctoral research fellow at the department of Molecular and Cell Biology of the University of the Witwatersrand. In 2019, he completed his PhD at the University of Antwerp in plant systems Biology. His work focuses on the identification of disease resistance genes in cassava such as NLR encoding proteins. These genotypes can be selected by farmers and be used in breeding techniques for better improvement of cassava crops against CMD.

    Title: Structural and functional characterization of NLRs proteins differentially expressed in Cassava plant inoculated with SACMV

    Dr Dylan Zeiss (University of Johannesburg) – a post-doctoral research fellow at the University of Johannesburg. He then enrolled for an MSc in Biochemistry that was upgraded to a Doctoral degree in 2019. He graduated in 2020. His research focuses on plant-microbe interactions and how this knowledge may have applications within the South African agricultural sector for sustainable food production. Has used a metabolomics-based approach using liquid chromatography coupled to mass spectrometry (LC-MS) in combination with statistical modelling to monitor specialized plant metabolism in response to R. solanacearum infection.

    Title: Metabolomic insights into the deployment of phytochemical defences in the tomato – Ralstonia solanacearum pathosystem

    Dr David L. Nsibo (University of Pretoria)- currently a Lecturer at the Department of Plant and Soil Sciences of the University of Pretoria. In 2019, he completed his PhD in Plant Science at the Department of Plant and Soil Sciences, University of Pretoria and graduated in April 2020. His research is aimed at determining the extent and patterns of genetic variation in populations of foliar pathogens of cereals and to understand how these pathogens cause disease using an array of innovative molecular- and genomics-based tools.

    Title: Population genetics of foliar pathogens of maize and the future of food and agriculture

    Dr Advaita Singh (Council for Scientific and Industrial Research) – a researcher in the Biomanufacturing Technology Demonstration Group at the Council for Scientific and Industrial Research (CSIR), the largest R&D institution in Africa. He has qualifications from the University of the Witwatersrand and the University of Pretoria, having qualified as a protein biochemist. His expertise lies in the development of recombinant processes to produce biopharmaceuticals in various expression systems. Dr Singh forms part of a group which prioritizes supporting industry and other partners in the translation of technologies towards commercialization and impact.

    Title: Plant-based production of highly potent anti-HIV antibodies with engineered posttranslational modifications.

    The ACGT would like to thank you for all your suggestions on future webinars. Below are a few of the topics we hope to explore in the future as per your suggestions:

    • Genome editing
    • Biopharming
    • Drug discovery from Herbal Medicines
    • Trends in analytical methods of medicinal plants
    • Fermentation technology
    • Systems biology in plant sciences

    We look forward to hosting you on the next Plant Biotechnology Forum.

  • InnovateUK programme unearths beneficial mechanisms of novel agricultural biostimulants in the African agricultural staple maize

    16th Sep 2021

    An internationally funded consortium working towards increasing yield and nutritional value of staple crops in Africa recently concluded an InnovateUK-funded programme. Despite the restrictions on travel due to COVID-19, the programme delivered promising results after being initiated in November 2019. The consortium was led by the University of Edinburgh, in collaboration with Omnia Nutriology®, the University of Pretoria (through the African Centre for Gene Technologies) and the University of Johannesburg.

    An innovative approach was followed by combining high-throughput, high coverage metabolomics analyses of individual plant growth-promoting rhizobacteria (PGPR or biostimulant strains), as well as novel combinations of the strains. Analyses were also undertaken of maize plants grown under controlled conditions, as well as at different field sites in the main maize growing areas of South Africa, treated with the biostimulants. The field trials provided ample plant material for detailed analyses of metabolite changes between the treatments, and hence gave insights into the mechanisms by which these biostimulants increased yield and altered metabolites with direct association to yield and nutritional benefits of the staple.

    A number of programme outputs have been achieved, that will target different audiences in the academic and agricultural industries. Included are two review manuscripts (one published), three peer-reviewed manuscripts (in preparation), an interview article in the UK Crop Production Magazine, three conference presentations and a video for public dissemination (currently being finalized).

    In addition, a demonstration site for African smallholder farmers is also being planned and will be implemented as soon as South African COVID restrictions allow. The demonstration site will extend knowledge on general soil health and optimal maize growth to smallholder farmers (as an introduction); through hands-on experience as well as extension manuals.

    The programme established and strengthened ties between multiple research organizations, from both the academic and industry side, and has opened new avenues to further explore refinement of the biostimulants under study.

    The consortium would like to sincerely thank InnovateUK, the United Kingdom’s innovation agency; as well as Omnia Nutriology®, for providing financial support to make the research programme possible.

     

     

  • AgriMicrobiomics workshop highlights African and international critical mass in food systems research

    AgriMicrobiomics workshop highlights African and international critical mass in food systems research
    13th Sep 2021

    Microbiomics research can be leveraged to develop innovative solutions towards food systems research and development. International domain experts recently convened to deliberate the opportunities and blind spots in the soil-plant-food-human gut microbiomics nexus. The event was inclusive of domain experts in each of the areas in the food system, from production to consumption. Countries and institutions represented were South Africa (University of Pretoria, University of Stellenbosch and CapeBio Technologies), Austria (Graz University of Technology), Netherlands (Wageningen University and Research), Germany (Julius Kühn Institut and the Helmholtz German Research Center for Environmental Health), as well as the USA (University of Pittsburgh).

    The workshop was chaired by Professor Lise Korsten, Co-Director of the DSI-NRF Centre of Excellence in Food Security.  The workshop’s main aims were:

    1. to formally introduce this group of AgriMicrobiomics scientists from all over the globe to each other to encourage the creation of an AgriMicrobiome network
    2. to create a specialist group to collaborate on AgriMicrobiome research
    3. identify areas of collaboration amongst group members
    4. to seek and secure financial support for collaborative endeavours.

    The trans-disciplinary and complementary approach of the speakers allowed for the identification of multiple opportunities to explore the role of microbes along the whole food system. The diversity of technical approaches and expertise housed at the various institutions were clearly indicative of the collective strength of the group, who indicated goodwill and a strong willingness to collaborate on the interdependent issues the One Health concept is facing. Several possible multi-institutional projects were identified, and progress is already underway to conceptualize and submit programmes for financial support.

    The future focus of the group will be on the soil/water/commercial and indigenous crops/human gut interdependencies, following a One Health approach. The proposed work under discussion was relevant to multiple Sustainable Development Goals; including SDG1 (No Poverty), SDG 2 (Zero Hunger), SDG 4 (Quality Education), SDG 6 (Clean water and sanitation) as well as SDG 12 (Responsible Consumption and Production).

    The African Centre for Gene Technologies and the DSI/NRF Centre of Excellence in Food Security would like to thank the following speakers for their time and highly constructive inputs during the event:

    1. Professor Lise Korsten, University of Pretoria
    2. Professor Don Cowan, Centre for Microbial Ecology and Genomics, University of Pretoria
    3. Professor Gabriele Berg, Graz University of Technology
    4. Professor Leo van Overbeek, Wageningen University and Research
    5. Professor Kornelia Smalla, Julius Kühn Institut
    6. Professor Michael Schloter, Helmholz Center Munich
    7. Stephen O’Keefe, African Microbiome Institute, University of Stellenbosch and University of Pittsburgh
    8. Dr Mubanga Kabwe, CapeBio Technologies
    9. Dr Jarishma Gokul, Department Plant and Soil Sciences, University of Pretoria.

    Keep an eye out for future events, inclusive of discussion sessions and online training, in the field of AgriMicrobiomics.

    The Organising Committee:
    Prof Lise Korsten
    Dr Jarishma Gokul
    Mr Molati Nonyane
    Dr John Becker

  • UP researchers seek to apply Biotechnology in the Agricultural Production Sector and Food Safety

    25th Jun 2021

    The ACGT hosted a webinar on the 28th of May 2021 presented by Dr Godfrey Kgatle and Ms Thabang Msimango from the University of Pretoria (UP). The webinar focused on how biotechnology can be used to curb the detrimental effects of micro-organisms in the Agricultural production sector.

     

    Dr Kgatle, a plant pathologist based at UP’s Forestry and Agricultural Biotechnology Institute, is currently looking at creating baseline knowledge that is needed in order to address and refine management strategies for crop diseases. Dr Kgatle detailed how his work focuses on determining the distribution of crop diseases as well as surveilling potential emerging diseases. Dr Kgatle has been on 12 field trips so far in 2021. These field trips were aimed at building a collection of isolates associated with grain crops as well as building a catalogue of photographs of maize diseases. Dr Kgatle highlighted the need for a transdisciplinary research approach in combating plant diseases.

     

    Ms Msimango’s presentation focused on how biotechnology can contribute to food safety. She presented her previous work that investigated the prevalence and characteristics of foodborne pathogens that were isolated from food that was supplied through school feeding programmes in South Africa. After analyzing samples from the water, fresh produce, soil, surfaces and hand swabs at the schools, Ms Msimango found the presence of E. coli and Staphylococcus aureus that exceeded normal levels. She also found that most of the E. coliisolates, detected mostly on fresh produce, were multi-drug resistant. Ms Msimango’s work indicated the need for improved food safety and sanitation strategies were food is prepared at the schools.

     

    Following the discussions from the Q&A session after the presentations, Dr Kgatle emphasized the need for better non-invasive seed screening methods that would insure that the planted seeds are not diseased. The ACGT and Dr Kgatle will be looking at phenomics tools that could be utilized to screen seeds in order to give farmers a better yield.

     

    Please see the following links for the webinar recording as well as the pdf of the presentations.
    Webinar recording: Click here
    Presentation PDF: Click here 

    Story by: ACGT

  • Africa has highest global death rate among critically ill COVID-19 patients – UP experts part of landmark study

    31st May 2021

    Mortality in critically ill patients with COVID-19 is higher in African countries than reported from studies done in Asia, Europe, North America and South America. This is according to the findings of a study that was conducted by a team of African researchers, including experts from the University of Pretoria (UP), and recently published in peer-reviewed journal The Lancet.

    Increased mortality was associated with insufficient critical-care resources, as well as comorbidities such as HIV/AIDS, diabetes, chronic liver disease and kidney disease, and the severity of organ dysfunction upon admission.

    “Our study is the first to give a comprehensive picture of what is happening to people who are severely ill with COVID-19 in Africa, with data from multiple countries and hospitals,” says Professor Bruce Biccard of Groote Schuur Hospital in Cape Town and the University of Cape Town, who co-led the research. “Sadly, it indicates that our ability to provide sufficient care is compromised by a shortage of critical-care beds and limited resources within intensive-care units [ICU].”

    Prof Biccard added that poor access to potential life-saving interventions such as dialysis, proning (turning patients onto their stomachs to improve breathing) and blood oxygen monitoring could be factors in the deaths of these patients, and could also partly explain why one in eight patients had therapy withdrawn or limited. “We hope these findings can help prioritise resources and guide the management of severely ill patients – and ultimately save lives – in resource-limited settings around the world.”

    Until now, little had been known about how COVID-19 was affecting critically ill patients in Africa, as there have been no reported clinical outcomes data from Africa or any patient management data in low-resource settings. To address this evidence gap, the African COVID-19 Critical Care Outcomes Study (ACCCOS) aimed to identify which human and hospital resources, underlying conditions and critical-care interventions might be associated with mortality or survival in adults (aged 18 or older) admitted to intensive-care or high-care units in Africa.

    The study focused on 64 hospitals in 10 countries (Egypt, Ethiopia, Ghana, Kenya, Libya, Malawi, Mozambique, Niger, Nigeria and South Africa). Between May and December 2020, about half (3 752 of 6 779) of patients with suspected or confirmed COVID-19 infection referred to critical care were admitted. Of those, 3 140 patients participated in the study. All received standard care and were followed up for at least 30 days unless they died or were discharged. Modelling was used to identify risk factors associated with death.

    After 30 days, almost half (48% – 1 483/3 077) of the critically ill patients had died. The analysis estimates that death rates in these patients were 11% (in best-case scenarios) to 23% (in worst-case scenarios) higher than the global average of 31.5%.

    “This collaborative landmark effort provides valuable information regarding the African COVID-19 experience among our critically ill patients,” says Prof Fathima Paruk, Clinical and Academic Head of the Critical Care Department at UP and the UP study site lead. “Unique findings – such as the high death rate, being male not being associated with a higher risk of death, ICU bed shortages, underuse of resources or a paucity of certain ICU resources – highlight the importance and need for our own data.”

    Clinical services and critical care to patients revealed some important information. Prof Paruk and her team at UP’s Faculty of Health Sciences and Steve Biko Academic Hospital in Pretoria played a leading role in this important study. The impact of their findings will not only be seen on clinical training platforms, but will have an impact on patient care in Africa, says Prof Tiaan de Jager, Dean of UP’s Faculty of Health Sciences.

    “Moving forward,” Prof Paruk adds, “the findings provide much-needed evidence in terms of guiding clinical management and in terms of the pressing need to ensure the appropriate provision, allocation and use of resources, so that we can save more lives in resource-limited settings. Furthermore, the high death rate among severely ill COVID-19 patients in Africa further strengthens the case for prevention through vaccination.”

    “Africans are clearly at higher risk of more severe disease and death when COVID-19 positive,” adds Prof Robin Green, Chairman of the School of Medicine at UP. “This suggests that our population is desperately in need of better ICU resources and medications, but especially prevention through vaccination. The current vaccine roll-out in Africa is hopelessly ineffective. We would appeal to all humanitarian and health agencies to make vaccines for Africa a priority.”

    “The Faculty of Health Sciences at UP, in particular our staff, has been at the forefront of the COVID-19 response,” says Prof De Jager. “The faculty has been preparing for this through the creation of research-driven teaching and learning platforms, informed by the demands of the fourth industrial revolution.”

    Story by: Prof Fathima Paruk, for the University of Pretoria 

  • Stress-Response Compound Widespread in Animals Is Found in Plants

    31st May 2021

    molecule made famous by its association with human heart disease and marine animals’ ability to survive high-pressure conditions turns out to be made by plants too, researchers report this week (May 19) in Science Advances. As it does in animals, trimethylamine N-oxide (TMAO) helps plants cope with stressful conditions, according to the study. The authors have already licensed the discovery to a company that is working to commercialize TMAO as a way to boost yields in agriculture.

    “Nobody has published before that plants have TMAO in the tissues,” says study coauthor Rafael Catalá of the Centro de Investigaciones Biológicas (CIB) Margarita Salas in Madrid.

    The new study grew out of earlier work in which Catalá and his colleagues looked for genes in the model plant Arabidopsis thaliana whose expression was changed by exposure to cold. One gene they found turned out to code for a type of enzyme called a flavin-containing monooxygenase (FMO) called FMOGS-OX5. In further analyses, reported in the current study, the team found that the expression of several other FMOgenes is also dialed up in Arabidopsis in response to cold.

    FMOs are known to make TMAO in animals in response a variety of stressors. Wondering what the connection was between the FMOs and the plant’s cold response, the team used nuclear magnetic resonance to look for TMAO in wildtype Arabidopsis. They found it, and confirmed its presence with liquid chromatography–tandem mass spectrometry. The team also verified that FMOGS-OX5 can generate TMAO from its precursor, TMA, in vitro.

    In animals, TMAO functions as an osmolyte, a type of molecule cells use to maintain the properties of their fluid and prevent proteins from becoming misfolded when confronted with conditions such as high salt concentrations. To see whether it plays a similar role in plants, Catalá and his colleagues treated Arabidopsisroots with tunicamycin, a compound that makes proteins unfold, as can happen under abiotic stress conditions such as cold or lack of water. The tunicamycin made the roots grow more slowly, but this effect was mitigated if the roots were grown in medium supplemented with TMAO, the researchers report.

    When the researchers engineered Arabidopsis to overexpress FMOGS-OX5, the plant also increased the expression of 184 other genes, many of which had been previously linked to responses to abiotic stressors, the authors report. Applying TMAO to wildtype plants had a similar effect on gene expression, although it did not change FMOGS-OX5’s expression level, suggesting that TMAO acts downstream of FMO to enhance the expression of stress-response genes.

    To find out whether TMAO is widespread in plant species, the team also looked for it in tomato, maize, barley, and a relative of tobacco, and found it was present in all of them. Moreover, their TMAO content rose when the plants were subjected to conditions of low water, high salt, or low temperatures (except barley, in which TMAO did not increase in the high-salt test but did in the other conditions). Spraying or watering tomato plants with a TMAO-containing solution made them visibly healthier, with more leaves, when they were exposed to each of the three stress conditions.

    Catalá says externally applied TMAO has the potential to be “a very powerful tool for agriculture.” He and the paper’s senior author, Julio Salinas, also of the CIB Margarita Salas, have filed patents on the agricultural use of TMAO, which is being commercialized by the company Plant Response. The company’s field tests have had good results, Catalá adds.

    Paul Verslues, who studies plant drought response at the Academia Sinica in Taipei, Taiwan, questions whether TMAO will be useful agriculturally. “TMAO protection of protein folding may be relevant to plant survival of severe stress but it is unknown whether it is also beneficial to protecting plant growth under less severe drought or salinity stress,” he writes in an email to The Scientist. The stresses the researchers subjected the plants to were too harsh to be reflective of agricultural conditions, and more experiments would be needed to determine whether TMAO also helps plants cope with milder stress conditions.

    Verslues also notes other reservations about the study’s findings, including that Arabidopsis made to overexpress FMOGS-OX5 had greater stress tolerance than did wildtype plants but did not accumulate more TMAO, which he says suggests that FMOs may “also produce some other compound that promotes stress tolerance” apart from TMAO. Additionally, the authors did not take the step of knocking out all of a plant’s FMO genes to test whether those genes are truly required for TMAO production in plants.

    Catalá argues that the study’s main finding, that TMAO exists in plants and has “a key role in plant tolerance to abiotic stress,” stands without testing such mutants. And he says it’s likely that FMOs do indeed produce other compounds involved in the stress response, but that the paper shows they are involved in making TMAO and that TMAO enhances stress tolerance.

    Aleksandra Skirycz, a plant biologist at the Boyce Thompson Institute who was not involved in the study, calls it “a very nicely designed story.” For her, the “really exciting aspect of this work is that you have a molecule that would work as an osmolyte for protection [and] at the same time would probably have other signaling functions,” a phenomenon she calls “moonlighting.” It’s not yet clear how TMAO influences gene expression, Catalá says, and that will be an avenue for the group to pursue in the future.

    In the biomedical literature, TMAO tends to come up in a negative context rather than a positive one, as high levels of it in patients’ blood have been linked to an elevated risk for blood clots. Studies have suggested that gut microbes break down choline, a nutrient present in high levels in meat, to generate TMAO and related compounds, providing a mechanistic link between a meat-heavy diet and risk of heart attack and stroke. Catalá says it’s not at all clear what implications, if any, the finding of TMAO in plants could have for human diet and health.

    Story by: Shawna Williams for The Scientist 

  • Exploring CAR T-cell therapy to treat breast cancer

    Exploring CAR T-cell therapy to treat breast cancer
    31st May 2021

    Credit: NIH

    Peter Mac researchers are developing a potential new way to make CAR T-cell therapy more effective against breast cancer and other solid cancers.

    CAR T-cell therapy is a type of immunotherapy where a patient’s own immune cells are collected and reengineered, before being infused back into the patient to fight their cancer.

    But CAR T-cells also contain a gene that can suppress this immune response. A Peter Mac-led study into this phenomenon has just been published in the scientific journal Nature Communications.

    “Cancer hijacks these pathways to shut off an immune response that would otherwise be beneficial,” says Dr. Paul Beavis, one of the senior authors of the study.

    Using a gene editing technique known as CRISPR, Dr. Beavis and his team were able to show that by knocking out this gene, CAR T-cell therapy was significantly more effective at fighting breast cancer.

    While the research has so far only been conducted using mice and human CAR T-cells in mice models, Dr. Beavis is confident it has the potential to progress to clinical trials, particularly as the sort of procedures they’ve been using have been used in clinical trials elsewhere…

    (To access the rest of the article please use the following link: MedicalXpress.com)

     

  • “Rogue” Protein Could Contribute to Humans’ High Cancer Rates

    “Rogue” Protein Could Contribute to Humans’ High Cancer Rates
    23rd Apr 2021

    A tissue section from a prostate cancer patient who produces Siglec-XII (stained brown), which is much more highly expressed in malignant cells than normal cells.
    FASEB BIOADVANCES, DOI:10.1096/FBA.2020-00092, 2020

    Among a group of cell surface proteins known as sialic-acid-binding immunoglobulin-like lectins (Siglecs), CD33-related Siglecs are found mainly on innate immune cells and are involved in cell signaling. One Siglec, however, appears to have “gone rogue” in humans, according to Ajit and Nissi Varki, a husband-and-wife team at the UC San Diego School of Medicine.

    Siglec-XII, encoded by the gene SIGLEC12, no longer binds sialic acid and seems to be involved in abnormal cell signaling in humans, the researchers report. The Varkis argue that the protein plays a role in cancer progression and could help explain why humans have much higher rates of carcinoma—cancers that arise from epithelial cells, where Siglec-XII is abundant—than do other great apes.

    Only about 30 percent of humans produce this rogue protein; most people have a mutation that inactivates SIGLEC12. The Varkis and their colleagues found Siglec-XII in about 80 percent of carcinoma samples but in just 35 percent of normal tissues. When they forced production of Siglec-XII in a human prostate cancer cell line, the result was higher expression of cancer progression–related genes than in prostate cancer cells that lacked the protein. And comparing cohorts of cancer patients, the team found that functional SIGLEC12was associated with poor prognosis in late-stage colorectal cancer patients.

    “The study proposes very interesting hypotheses,” says Jun Wang, an immunologist at NYU Langone Health who was not involved in the research. But, he says, more evidence is needed to confirm Siglec-XII’s role in cancer progression because artificial overexpression of the protein in prostate cancer cells could differ from how the protein behaves in tumors. He notes that it would also be interesting to examine how Siglec-XII in immune cells contributes to cancer. “The cancer cell is just part of the puzzle. The whole picture is cancer and the immune system.”

    Story by: Asher Jones for The Scientist