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New Aston University spin-out company will develop novel ways to treat non-healing wounds
EVolution Therapeutics (EVo) has been founded on the work of Professor Andrew Devitt into the causes of inflammatory disease A failure to control inflammation in the body, usually a natural defence mechanism, can cause chronic inflammation, such as non-healing wounds Non-healing wounds cost the NHS £5.6bn annually, so there is a vital need for new treatments. Aston University’s Professor Andrew Devitt, Dr Ivana Milic and Dr James Gavin have launched a new spin-out company to develop revolutionary treatments to treat chronic inflammation in patients. One of the most common inflammatory conditions is non-healing wounds, such as diabetic foot ulcers, which cost the NHS £5.6bn annually, the same cost as managing obesity. Such wounds are generally just dressed, but clinicians say there is a vital need for active wound treatments, rather than passive management. The spin-out, Evolution Therapeutics (EVo), will aim to create these vital active treatments. Inflammation in the human body helps to fight infection and repair damage following injury and occurs when the immune system floods the area with immune cells. Normally, this inflammation subsides as the damage heals, with the immune system signalling to the immune cells to leave. However, in some cases, the usual healing mechanism is not triggered and the inflammatory response is not turned off, leading to chronic inflammation and so-called inflammatory diseases. EVo is based on Professor Devitt’s work on dying cells in the body, known as apoptotic cells, and how they contribute to health. Dying cells release small, membrane-enclosed fragments called extracellular vesicles (EVs), which alert the immune system to the death of cells, and then trigger the body’s natural repair mechanism and remove the dead cells. It is estimated that 1m cells die every second. Professor Devitt and his team have identified the molecules within the EVs which control the healing process and are engineering new EVs loaded with novel healing enzymes, to drive the body’s repair responses to actively heal wounds. Much of the research has been funded by the Biotechnology and Biological Sciences Research Council (BBSRC) with additional support from the Dunhill Medical Trust. Professor Devitt, Dr Milic and Dr Gavin received Innovation-to-Commercialisation of University Research (ICURe) follow-on funding of £284,000 to develop the vesicle-based therapy with EVo. Most recently, in December 2023, Professor Devitt and Dr Milic were awarded £585,000 from the BBSRC Super Follow-on-Fund to develop engineered cells as a source of membrane vesicles carrying inflammation controlling cargo. The team, together with Professor Paul Topham, also received funding from the National Engineering Biology Programme (£237,000) to support polymer delivery systems for vesicles. EVo is one of the 12 projects being supported by SPARK The Midlands, a network which aims to bridge the gap between medical research discoveries of novel therapeutics, medical devices and diagnostics, and real-world clinical use. SPARK The Midlands is hosted at Aston University, supported by the West Midlands Health Tech Innovation Accelerator (WMHTIA), and was launched at an event on 31 January 2024. Professor Devitt, EVo chief technical officer, said: “Inflammation is the major driver of almost all disease with a huge contribution to those unwelcome consequences of ageing. We are now at a most exciting time in our science where we can harness all the learning from our research to develop targeted and active therapies for these chronic inflammatory conditions.” Dr Gavin, EVo CEO, said: “The chronic inflammation that results in non-healing wounds are a huge health burden to individuals affecting quality of life as we age but also to the economy. Our approach at EVo is to target the burden of non-healing wounds directly to provide completely novel approaches to wound care treatment. By developing a therapy which actively accelerates wound healing, we hope to drastically improve quality of life for patients, whilst reducing the high cost attached to long term treatment for healthcare systems worldwide.”

Research: Add space salad to the risks astronauts face
University of Delaware researchers grew lettuce under conditions that imitated the weightless environment aboard the International Space Station and found those plants were actually more prone to infections from Salmonella. It’s been more than three years since the National Aeronautics and Space Administration made space-grown lettuce an item on the menu for astronauts aboard the International Space Station. Alongside their space diet staples of flour tortillas and powdered coffee, astronauts can munch on a salad, grown from control chambers aboard the ISS that account for the ideal temperature, amount of water and light that plants need to mature. But as the UD researchers discovered, there is a problem. The International Space Station has a lot of pathogenic bacteria and fungi. Many of these disease-causing microbes at the ISS are very aggressive and can easily colonize the tissue of lettuce and other plants. Once people eat lettuce that’s been overrun by E. coli or Salmonella, they can get sick. With billions of dollars poured into space exploration each year by NASA and private companies like SpaceX, some researchers are concerned that a foodborne illness outbreak aboard the International Space Station could derail a mission. In the new study by UD's team, published in Scientific Reports and in npj Microgravity, researchers grew lettuce in a weightless environment similar to that found at the International Space Station. Plants are masters of sensing gravity, and they use roots to find it. The plants grown at UD were exposed to simulated microgravity by rotation. The researchers found those plants under the manufactured microgravity were actually more prone to infections from Salmonella, a human pathogen. Stomata, the tiny pores in leaves and stems that plants use to breathe, normally close to defend a plant when it senses a stressor, like bacteria, nearby, said Noah Totsline, an alumnus of UD’s Department of Plant and Soil Sciences who finished his graduate program in December. When the researchers added bacteria to lettuce under their microgravity simulation, they found the leafy greens opened their stomata wide instead of closing them. “The fact that they were remaining open when we were presenting them with what would appear to be a stress was really unexpected,” Totsline said. Totsline, the lead author of both papers, worked with plant biology professor Harsh Bais as well as microbial food safety professor Kali Kniel and Chandran Sabanayagam of the Delaware Biotechnology Institute. The research team used a device called a clinostat to rotate plants at the speed of a rotisserie chicken on a spinner. “In effect, the plant would not know which way was up or down,” Totsline said. “We were kind of confusing their response to gravity.” Additionally, Bais and other UD researchers have shown the usage of a helper bacteria called B. subtilis UD1022 in promoting plant growth and fitness against pathogens or other stressors such as drought. They added the UD1022 to the microgravity simulation that on Earth can protect plants against Salmonella, thinking it might help the plants fend off Salmonella in microgravity. Instead, they found the bacterium actually failed to protect plants in space-like conditions, which could stem from the bacteria’s inability to trigger a biochemical response that would force a plant to close its stomata. “The failure of UD1022 to close stomata under simulated microgravity is both surprising and interesting and opens another can of worms,” Bais said. “I suspect the ability of UD1022 to negate the stomata closure under microgravity simulation may overwhelm the plant and make the plant and UD1022 unable to communicate with each other, helping Salmonella invade a plant.” To contact researchers from the team, visit the profiles for Bais or Kniel and click on the contact button.

Image shows how tiny water channels control how water enters and exits cells through their membranes The Aston Institute for Membrane Excellence (AIME) will be set up with a £10m grant from Research England AIME will be led by Professor Roslyn Bill from Biosciences and Professor Paul Topham from Chemical Engineering and Applied Chemistry The globally unique institute will use biomimetic polymer membranes for applications such as water purification and drug development Aston University will establish the Aston Institute for Membrane Excellence (AIME), a globally unique, cross-disciplinary institute to develop novel biomimetic membranes, after receiving a major grant of £10m from Research England. AIME will be led by Professor Roslyn Bill, from the School of Biosciences, with co-lead Professor Paul Topham from the department of Chemical Engineering and Applied Chemistry (CEAC). Membranes, both biological and synthetic, are hugely important in many sectors. For example, the world’s top ten selling human medicines all target proteins in biological membranes, while synthetic polymer membranes are used in the US$100bn/year water purification industry. The team behind AIME believes that the full potential of membranes will only be realised by an interdisciplinary group spanning biology, physics and chemistry that can investigate membranes holistically. Professor Bill, a European Research Council (ERC) Advanced grantee leads Aston Membrane Proteins and Lipids (AMPL) research centre of excellence that studies the structure and function of membrane proteins and associated lipids. Professor Topham leads Aston Polymer Research Group (APRG), which investigates the nanoscale behaviour of block copolymers (a type of polymer with a structure made of more than one type of polymer molecule) and polymer technologies for membranes. AMPL and APRG have already begun collaborative research and AIME will bring together the complementary expertise of both research clusters into one institute. AIME will initially comprise the eight researchers from AMPL and APRG. Alongside the co-leads Professor Bill and Professor Topham, will be Dr Alan Goddard, Professor Andrew Devitt, Professor Corinne Spickett, Dr Alice Rothnie, Dr Matt Derry and Dr Alfred Fernandez. It plans to recruit three further academics, six tenure-track research fellows, three postdoctoral research assistants (PDRAs), six PhD students, a research technician and a business development manager. Importantly, AIME will work with many existing Aston University colleagues to build a comprehensive research community focused on all aspects of membrane science. The new AIME team will focus on the development of bioinspired, highly selective polymer structures for applications in water purification and waste remediation, nanoparticles loaded with therapeutic molecules to treat disorders ranging from chronic wounds to neurological injuries, and the purification of individual membrane proteins with polymers to study them as drug targets. The vision is for AIME to become a ‘one-stop shop’ for interdisciplinary, translational membrane research through its facilities access and expertise, ideally located in the heart of the country. Professor Bill said: “The creation of AIME is ground-breaking. Together with Aston’s investment, E3 funding will deliver a step-change in scale and the rate at which we can grow capacity. We will address intractable scientific challenges in health, disease, and biotechnology, combining our world-class expertise in polymer chemistry and membrane biology to study membranes holistically. The excellence of our science, alongside recent growth in collaborative successes means we have a unique opportunity to deliver AIME’s ambitious and inclusive vision.” Professor Topham said: “We are really excited by this fantastic opportunity to work more closely with our expert colleagues in Biosciences to create advanced technology to address real world problems. From our side, we are interested in molecular engineering, where we control the molecular structure of new materials to manipulate their properties to do the things that we want! Moreover, we are passionate about a fully sustainable future for our planet, and this investment will enable us to develop technological solutions in a sustainable or ‘green’ way.” Professor Aleks Subic, Vice-Chancellor and Chief Executive of Aston University, says: “Our new Aston Institute for Membrane Excellence (AIME) will be a regional, national, and international research leader in membrane science, driving game-changing research and innovation that will produce a pipeline of high-quality research outcomes leading to socioeconomic impact, develop future global research leaders, create advanced tech spinout companies and high value-added jobs for Birmingham and the West Midlands region. Its establishment aligns perfectly with our 2030 strategy that positions Aston University as a leading university of science, technology and enterprise.” Steven Heales, Policy Manager (Innovation) at the West Midlands Combined Authority, said: “WMCA is delighted to see Research England back the Aston Institute for Membrane Excellence. This will enable Aston University’s excellent academics and research community to work closely with businesses to make advances in membrane technology and applications. “In 2023 the West Midlands Combined Authority agreed a Deeper Devolution Trailblazer Deal with Government, which included a new strategic innovation partnership with Government. Projects like AIME are exactly the kind of impact we expect this new partnership to generate, so watch this space.” Lisa Smith, chief executive of Midlands Mindforge, the patient capital investment company formed by eight Midlands research-intensive universities including Aston University, said: “This grant is an important vote of confidence in the Midlands scientific R&D ecosystem. AIME will play an important role in the future research of pioneering breakthroughs in membrane science and enable the world-leading research team at Aston University to develop solutions to real world problems. We look forward to closely working with the Institute and nurturing best-in-field research being undertaken at Aston out of the lab and into the wider society so it can make a positive impact”. Rob Valentine, regional director of Bruntwood SciTech, the UK’s leading developer of city-wide innovation ecosystems and specialist environments and a strategic partner in Birmingham Innovation Quarter, said: "As a proud supporter of the Aston Institute for Membrane Excellence (AIME), I am thrilled at the launch of this groundbreaking initiative. AIME exemplifies Aston University's commitment to advancing cutting-edge interdisciplinary research and further raises the profile of the region’s exemplary research capabilities and sector specialisms. AIME's vision of becoming a 'one-stop shop' for translational membrane research, strategically located at the heart of the country, aligns perfectly with our strategy at Bruntwood SciTech. We are committed to working with partners, including Aston University, to develop a globally significant innovation district at the heart of the UK where the brightest minds and most inspiring spaces will foster tomorrow’s innovation.” Membrane research at Aston University has also recently received two other grants. In November 2023, Professor Bill received £196,648 from the Biotechnology and Biological Sciences Research Council’s Pioneer Awards Scheme to understand how tiny membrane water channels in brain cells keep brains healthy. In December 2023, a team led by AIME team-member Dr Derry received £165,999 from the Engineering and Physical Sciences Research Council to develop biomimetic membranes for water purification. For more information about AIME, visit the webpage.

An interdisciplinary team from Georgia Southern University was awarded more than $465,000 from the National Academies of Sciences, Engineering, and Medicine to foster the development of scientific and environmental skills that are critical to solving complex issues in the Gulf of Mexico region now and into the future. The award is part of an initiative with the Gulf Research Program (GRP) that awarded $2 million to eight projects that engage children and youth in place-based educational activities. The funded project, “Suwannee Watershed: Assessment and Monitoring of Place to Gain Understanding of Local Flow (SWAMP to GULF),” is led by principal investigator (PI) Lacey Huffling, Ph.D., associate professor of science education, and co-PIs Heather Scott, Ed.D., and Regina McCurdy, Ph.D., both assistant professors of science education. (l-r) College of Education’s Lacey Huffling, Ph.D., Regina McCurdy, Ph.D., and Heather Scott, Ed.D., are part of an interdisciplinary team awarded $465k to train science teachers in the Gulf of Mexico. “I am honored that we were selected to receive funding from the Gulf Research Board,” said Huffling. “Over the past four years, we have developed a strong network of Georgia middle and high school teachers who are dedicated to developing the science and environmental literacy of their students through watershed citizen science, specifically focused on areas of Georgia that flow into the Gulf of Mexico. We are excited to continue to grow this network of teachers in Florida further to foster scientific and environmental literacy of future generations to monitor and advance scientific and community understanding of the Lower Suwannee Watershed.” The group will train and support teachers in Florida to implement place-based learning through citizen science using communities as classrooms to deepen teachers’ and students’ sense of place and connection to local watersheds; research how teachers and students address local issues and solve problems by using and developing their critical environmental agency; and increase participation of rural populations in science, which have historically been underrepresented. This initiative, along with the seven other GRP projects, will help connect young learners across the Gulf of Mexico region with local environmental issues and work toward the betterment of the region at large. “The goal of these grants is to empower young learners through place-based education, an interdisciplinary, student-centered, inquiry-driven teaching and learning practice situated in the local community and environment,” said Karena Mary Mothershed, senior program manager for the GRP’s Board on Gulf Education and Engagement. “These eight projects have a high potential to create long-lasting impacts on underserved students in grades K-8 across the Gulf of Mexico region, enabling them to consider and address environmental challenges impacting their own communities.” Additional SWAMP to GULF project members include Georgia Southern staff and faculty: Mary Thaler, senior administrative assistant for the Center for STEM Education; J. Checo Colón-Gaud, Ph.D., professor of biology and associate dean of the Jack N. Averitt College of Graduate Studies; Shainaz Landge, Ph.D., assistant professor of chemistry, Luke Roberson, coordinator of Community Engagement and Outreach for the Institute of Water and Health; and Asli Aslan, Ph.D., director of the Institute of Water and Health. Interested in learning more? Contact Georgia Southern's Director of Communications Jennifer Wise at jwise@georgiasouthern.edu to arrange an interview today.

Georgia Southern sets fundraising record for third year in a row
Total cash, pledges and in-kind gifts to Georgia Southern University amounted to $23,831,604 during Fiscal Year 2023, which ended on June 30, 2023. That surpasses the total from the previous year, which was also a record at $22.3 million. For the third straight year, Georgia Southern supporters have propelled the University to a record-breaking year of private fundraising. Total cash, pledges and in-kind gifts to Georgia Southern University amounted to $23,831,604 during Fiscal Year 2023, which ended on June 30, 2023. That surpasses the total from the previous year, which was also a record at $22.3 million. The record total was buoyed by another record-breaking fundraising year for the Georgia Southern Athletic Foundation, Inc., which raised a record $11.06 million in new pledges and outright gifts. “As we soar into a very bright future for this University, record-breaking fundraising is a sign that Georgia Southern is not only strong now, but poised for even greater heights,” said Georgia Southern President Kyle Marrero. “We are endlessly thankful for the supporters, friends, alumni and donors who endorse our path forward and are stepping up to ensure our success.” Donors helped with various projects and programs this past year, including: $1 million from Betty Foy Sanders for the Betty Foy Sanders School of Art with scholarships, travel and programmatic needs $750,000 deferred gift for the Department of Biology to be used for student scholarships 23 newly created endowments Anthony P. Tippins Family Training Facility for athletics “Through unwavering dedication and the overwhelming generosity of our community, we have demonstrated the boundless potential of Eagle Nation in support of our students’ dreams and the University’s future,” said Georgia Southern Foundation Chair Mike Sanders. Last year’s Athletic Foundation Chair Leonard Bevill added, “The impact of this achievement will ripple through generations, leaving an indelible mark on the trajectory of higher education and Georgia Southern. I am humbled and inspired by the collective spirit that has made this three-year milestone possible.” The Erk Russell Fund, the Athletic Foundation’s annual fund, continues to grow and saw donations of $3.2 million this fiscal year. Additionally, the Athletic Foundation received 58 major gift commitments this year, which are gift commitments of $25,000 or greater to support Eagle Athletics. Over the past three fiscal years, the Athletic Foundation has raised more than $27 million in support of Georgia Southern Athletics. This total is the largest three-year fundraising window in department history. “It’s clear that Georgia Southern University’s power to transform lives and communities is making a positive impression with our private supporters,” said Trip Addison, Vice President of Advancement, noting that more than 3,600 alumni were among the supporters this past year. “I am grateful for the welcome reception we are receiving when we ask people to join in our effort to help support our students and the work they and our faculty are doing.” Interested in knowing more about fundraising or to speak with Georgia Southern Foundation Chair Mike Sanders? To arrange an interview simply connect with Georgia Southern's Director of Communications Jennifer Wise at jwise@georgiasouthern.edu to arrange an interview today.

Georgia Southern University biology professor and researcher Christine Bedore, Ph.D., is helping National Geographic explore the mysteries of shark attacks by sharing her expertise and years of fieldwork as part of the six-part series, “When Sharks Attack 360,” this month. The series, which kicked off July 3, is part of National Geographic’s SharkFest, which will run all month on National Geographic TV, Disney+ and Nat Geo WILD, with new episodes each night through July 11. All episodes are currently available for streaming on Hulu. In episodes 3 and 6, Bedore, an assistant professor in the College of Science and Mathematics who conducts research on sensory systems in sharks, discusses how shark senses may lead to bites by sharks on humans. While filming, she marveled at the channel’s cutting-edge VFX lab and their approach to educating viewers. “Working with National Geographic and the production team on this series was exciting because of the level of experience and creativity of the production team,” said Bedore. “It’s one of the most unique experiences I’ve had filming a documentary so far since it was done in a studio with a green screen, rather than in the field like we typically do. Using the virtual graphics in this series allows us to see these animals from a completely different angle. Although it was challenging to point at a shark that I couldn’t see at the time, we wouldn’t be able to see the detail of the animal at this level filming in the field.” Sharks have long captured the attention of both scientists and the public, and are fascinating animals for many reasons, according to Bedore, who has offered her expertise for previous episodes on Nat Geo WILD, The History Channel and BBC. They’re a species of immense size and diversity, and offer unique behaviors and interactions with other creatures, she noted. Understanding the behavior and physiology of sharks is critical to their survival, as they experience population declines due to overfishing and habitat changes. “In order to combat these changes and ensure the persistence of sharks in our oceans across the world, we first need to understand why they behave the way that they do,” Bedore said. “This series helps us do exactly that. For example, in episode 3 we discuss whether or not sharks can see in color. As a scientist that studies shark color vision, I’m often approached with the question, ‘who cares if sharks can see color?’ As you’ll see, the ability to see color could help sharks identify prey, predators or other objects.” In episode 6, Bedore helps viewers understand that visual acuity, or how clear an image is, may be more important than color when we think about why sharks sometimes have negative interactions with humans. “Being able to discuss my work in these areas through National Geographic’s shark month has been a rewarding experience in helping people understand why these events sometimes happen,” she said. “It’s exciting to study such charismatic animals and have the chance to share your enthusiasm for your research and the sharks with people across the world.” For more information on National Geographic’s “When Sharks Attack 360” visit here. The series can be seen on Hulu, Disney+ and Nat Geo WILD throughout July. To connect with Georgia Southern University biology professor and researcher Christine Bedore to learn more about this fascinating topic - simply contact Georgia Southern's Director of Communications Jennifer Wise at jwise@georgiasouthern.edu to arrange an interview today.
Expert comment on new NHS childhood obesity clinics
Dr Duane Mellor, Senior Teaching Fellow, Centre for Health & Society Aston Medical School and Associate Dean Public Engagement is available for comment on new NHS childhood obesity clinics "It would be about supporting the whole person living with obesity alongside their family. It is important that higher body weight is not a choice, but the result of biology and our modern environment. Families and young people need support to make healthier lifestyle choices easier. We need to focus on kind and effective ways to improve health, weight change is just a product when health behaviours change and should not be seen as the only or main aim." For more details contact Nicola Jones Press and Communications Manager 07825 342091 or n.jones6@aston.ac.uk

• Has potential to help geneticists investigate vital issues such as antibacterial resistance • Will untangle the genetic components shared due to common ancestry from the ones shared due to evolution • The work is result of a four-year international collaboration. Aston University has worked with international partners to develop a software package to help scientists answer key questions about genetic factors associated with shared characteristics among different species. Called CALANGO (comparative analysis with annotation-based genomic components), it has the potential to help geneticists investigate vital issues such as antibacterial resistance and improvement of agricultural crops. This work CALANGO: a phylogeny-aware comparative genomics tool for discovering quantitative genotype-phenotype associations across species has been published in the journal Patterns. It is the result of a four year collaboration between Aston University, the Federal University of Minas Gerais in Brazil and other partners in Brazil, Norway and the US. Similarities between species may arise either from shared ancestry (homology) or from shared evolutionary pressures (convergent evolution). For example, ravens, pigeons and bats can all fly, but the first two are birds whereas bats are mammals. This means that the biology of flight in ravens and pigeons is likely to share genetic aspects due to their common ancestry. Both species are able to fly nowadays because their last common ancestor – an ancestor bird - was also a flying organism. In contrast, bats have the ability to fly via potentially different genes than the ones in birds, since the last common ancestor of birds and mammals was not a flying animal. Untangling the genetic components shared due to common ancestry from the ones shared due to common evolutionary pressures requires sophisticated statistical models that take common ancestry into account. So far, this has been an obstacle for scientists who want to understand the emergence of complex traits across different species, mainly due to the lack of proper frameworks to investigate these associations. The new software has been designed to effectively incorporate vast amounts of genomic, evolutionary and functional annotation data to explore the genetic mechanisms which underly similar characteristics between different species sharing common ancestors. Although the statistical models used in the tool are not new, it is the first time they have been combined to extract novel biological insights from genomic data. The technique has the potential to be applied to many different areas of research, allowing scientists to analyse massive amounts of open-source genetic data belonging to thousands of organisms in more depth. Dr Felipe Campelo from the Department of Computer Science in the College of Engineering and Physical Sciences at Aston University, said: “There are many exciting examples of how this tool can be applied to solve major problems facing us today. These include exploring the co-evolution of bacteria and bacteriophages and unveiling factors associated with plant size, with direct implications for both agriculture and ecology.” “Further potential applications include supporting the investigation of bacterial resistance to antibiotics, and of the yield of plant and animal species of economic importance.” The corresponding author of the study, Dr Francisco Pereira Lobo from the Department of Genetics, Ecology and Evolution at the Federal University of Minas Gerais in Brazil, said: “Most genetic and phenotypic variations occur between different species, rather than within them. Our newly developed tool allows the generation of testable hypotheses about genotype-phenotype associations across multiple species that enable the prioritisation of targets for later experimental characterization.” For more details about studying computer since at Aston University visit https://www.aston.ac.uk/eps/informatics-and-digital-engineering/computer-science

Discovery may lead to more precise treatments for advanced colorectal cancer Researchers at ChristianaCare’s Cawley Center for Translational Cancer Research at the Helen F. Graham Cancer Center & Research Institute have demonstrated for the first time that microRNA (miRNA) expression leads to a diversity of cancer stem cells within a colorectal cancer tumor. This diversity of cancer cells may explain why advanced colorectal cancer is difficult to treat. Study results have been in the Journal of Stem Cell Research and Therapy. The findings broaden the understanding of how miRNA expression adds to cancer stem cell diversity and may lead to more precise anti-cancer treatments for patients with advanced colorectal cancer. The research builds on prior discoveries by scientists at the Graham Cancer Center about how cancer stem cell activity contributes to the development and spread of colorectal cancer. “Our research shows — at least in the laboratory — that there are different subpopulations of cancer stem cells in a tumor, and they may be driving the growth of the cancer,” said Principal Investigator Bruce Boman, M.D., Ph.D., MSPH, FACP, medical director of Cancer Genetics and Stem Cell Biology at the Graham Cancer Center. “In one subpopulation of cancer stem cells, its miRNA will shut down the stem cell genes that are expressed in another subpopulation, and vice versa, within the same tumor.” From left: ChristianaCare researchers Lynn Opdenaker, Ph.D., Brian Osmond, Bruce Boman, M.D., Ph.D., Chi Zhang, Victoria Hunsu, Caroline Facey, Ph.D. Not pictured Victoria Stark, MS. The study focused on the composition of cancer stem cells within a colorectal cancer cell line (HT29) in the laboratory setting. Researchers evaluated the different cancer stem cell subpopulations that were identified by examining patterns of miRNA expression in each subpopulation and looking for differences. The researchers found that each of the four diverse subpopulations that were studied (ALDH, LRIG1, CD166 and LGR5) had a different miRNA expression or gene signature. The researchers found that miRNA expression could inhibit the expression of messenger RNA (mRNA), which carries instructions from the DNA to encode specific proteins within cells. Therefore, miRNA, by controlling gene expression, dictate which proteins are contained in the stem cells. The researchers discovered the miRNA that are upregulated in certain cancer stem cell subpopulations are downregulated in other cancer stem cell subpopulations. In this way, differential miRNA expression leads to cancer stem cell heterogeneity within colorectal tumor tissue. “It’s an early research finding and needs to be followed up with other experiments, but it has clear relevance to the clinic,” Boman said. “The question is: Can you target the miRNA to make cancer more sensitive to certain treatments? Because we know what the current anti-cancer treatments are targeting, we may be able to modulate or manipulate the cancer, so it becomes more sensitive to the treatment.” Identification of a network of genes regulated by microRNAs in a cancer stem cell subpopulation. For more than a decade, ChristianaCare’s researchers have contributed to the understanding of the role that cancer stem cells and miRNA expression play in the development and spread of colorectal cancer. This latest finding builds on earlier discoveries that examined a link between two cellular signaling pathways: retinoic acid (RA) signaling and wingless-related integration site (WNT) signaling, which are dysregulated by different gene mutations in colorectal tumors. The RA signaling pathway induces growth arrest and differentiation of cancer stem cells. Notably, retinoic acid is effective against other types of cancer such as leukemia. The role of the WNT signaling pathway has an opposite effect on tumor growth. The WNT signaling pathway is activated by a mutation in the APC (adenomatous polyposis coli) gene in about 90% of cases of colorectal cancer. In APC mutant tissue, dysregulated miRNA expression may underlie an imbalance between the RA and WNT signaling, which then leads to intratumoral cancer stem cell heterogeneity. Still, this mechanism that may enable the cancer to proliferate could also provide clues on how to more effectively treat cancer. “If you’ve got an imbalance between these two signaling pathways, then you’ve likely got a growth driver,” Boman said. “The question is: Can you suppress the WNT signaling and enhance the retinoic acid signaling?” It may be possible to increase the sensitivity of colorectal cancer to retinoic acid-type drugs, and therapeutically shift the balance between different cancer stem cell subpopulations, thereby suppressing cancer growth. More research is needed to determine how targeted cancer therapies containing retinoic acid-type drugs may be made more effective against advanced cancer. This research will be presented at the annual meeting of the American Association for Cancer Research in Orlando, Florida, April 14-19. This research project was supported by a grant from the Lisa Dean Moseley Foundation.

Protein engineer to explore route from DNA blueprint to synthetic antibodies – public lecture
Professor Anna Hine will explore how advances in protein engineering have enabled us to make both synthetic antibodies and their replacements Inaugural lecture will take place at Aston University on Tuesday 28 March 2023 at 6.30pm Members of the public may attend in person or online. Professor Anna Hine, a molecular biologist specialising in protein engineering in the College of Health and Life Sciences at Aston University, is to present her inaugural public lecture on Tuesday 28 March 2023. During her lecture, A route to synthetic antibodies (and their replacements), Professor Hine will take the audience from the basics of molecular biology to explaining her inventions in protein engineering, through to examining the ways in which her research is being applied internationally to develop synthetic antibodies. Professor Hine gained her PhD in molecular biology from The University of Manchester Institute of Science and Technology in 1992 and did her postdoctoral training at Harvard Medical School. She returned to the UK to take up a lectureship in molecular biology at Aston University in 1995. Professor Anna Hine, professor of protein engineering, said: “Antibodies are one of our major lines of defence against infection and we can create them very quickly to help incapacitate a multitude of biological invaders. Humans do this by changing the part of the antibody that recognises the invading pathogen, through a process of rapid, natural mutation. Protein engineers have learned to mimic this process in the laboratory to create synthetic proteins – particularly antibodies - for use in both therapy and fundamental research.” “I am delighted to have the opportunity to present our discoveries in a way that I hope will make just as much sense to non-scientists as to a scientific audience.” Similar to the natural mutation of antibodies, protein engineers can make vast numbers of tiny variations of a protein such as an antibody. Professor Hine added: “We will contemplate the vast numbers involved in protein engineering and present how our Aston University-based inventions have made the creation of DNA (and thus protein) ‘libraries’ as efficient as possible. “We will then examine the ensuing problem of how to find the few proteins that we really want from within a protein library. This includes collaborating with experts who specialise in computer-assisted library design and also working with those who have developed the latest methods to search the libraries that we make.” Professor Hine will also show how her latest collaborative projects are starting to move beyond the antibody itself. The lecture will take place at Aston University at 6.00pm for 6.30pm on Tuesday 28 March 2023. It will be followed by a drinks reception from 7.30 pm to 8.00 pm. The lecture is open to the public and free to attend. Places must be booked in advance via Eventbrite.




