It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Tuesday, July 01, 2025
Scientists target ‘molecular machine’ in the war against antimicrobial resistance
Scientists have studied a new target for antibiotics in the greatest detail yet – in the fight against antibiotic resistance
Credit: Dr Julien Bergeron - King's College London
Scientists have studied a new target for antibiotics in the greatest detail yet – in the fight against antibiotic resistance.
The ‘molecular machine’ flagellum is essential for bacteria to cause infection, allowing bacteria to ‘swim’ around the bloodstream until finding something to infect. But it could also be a target for antibiotics.
Impairing the flagellum would deliver a critical, but not fatal, blow to bacteria. This is a new approach and contrasts to traditional antibiotics, which are designed to kill all bacteria in their path.
Keeping bacteria alive could help to tackle, or at least significantly slow down the rate of antibiotic resistance. This is because there is less pressure for the bacteria to adapt and develop resistance to survive.
To develop this new approach, scientists first need to understand the enemy. Answering the call, researchers at King’s College London, have now studied the flagellum in its greatest detail to date.
The new study, published in Nature Microbiology today, addresses one of the most significant challenges to modern healthcare, antibiotic resistance. Drug-resistant infections are expected to claim more than 39 million lives between now and 2050 without further policy action, according to the Global Research on Antimicrobial Resistance Project.
Lead author Dr Julien Bergeron, King’s College London, said: “The flagellum is perhaps the most studied cellular machine, acting as a propeller, through the rotation of a long filament. It is also a major reason why bacteria cause disease; flagella give bacteria a competitive edge at causing disease and the presence of this molecule alone contributes to more than 100,000s deaths annually.
“We knew how important it was to study this ‘molecular machine’, as we investigate it as a potential target in our quest to neutralise the threat of bacteria.
“The bacterial flagellum has long fascinated scientists and the wider public alike. Yet, despite being extensively studied for over 70 years, the molecular details of its architecture have so far eluded researchers. This is because we simply haven’t had the tools.”
Dr Bergeron and his team used a state-of-the-art type of technique called cryo-electron microscopy – which reveals images of cells at an atomic level in impressive molecular detail. This enabled the team to understand how the flagellum forms, identifying areas to target with drugs. They had access to one of the most powerful electron microscopes, based at the Francis Crick Institute, available for scientists tackling some of the biggest challenges in healthcare – from antibiotic resistance to cancer.
Dr Bergeron explained: “In this study, we have used the world’s most advanced electron microscope to reveal the complete architecture of the bacterial flagellum, down to atomic levels of details. This unearthed unexpected intricacies in its structure. Critically, we were able to visualise the individual steps involved in the assembly of the flagellum, a process that until now had largely remained unexplained.”
Co-author Professor Marc Erhardt, from the Max Planck Unit for the Science of Pathogens and the Humboldt-Universität zu Berlin, Germany, also developed a vital ‘genetic trick’, enabling scientists to study a very short section of flagella in great detail. He said: “It was an extraordinary experience to capture snapshots of the flagellum forming that had previously remained hidden. Observing how individual flagellin molecules are folded and inserted into the growing filament was like decoding a molecular ballet.”
Further research is needed to fully understand how the flagellum forms, for example what triggers the initial process of its development. Scientists believe, however, it could be a key target to stop infections without driving resistance.
Dr Bergeron added: “This study will undoubtedly open new avenues towards the development of new treatments for bacterial infections. With the right funding and support this could become reality within a couple of years. However, realistically I think it would be more like a decade and we would need support from industry to help us in this fight against antimicrobial resistance.”
Dr Katie Edwards studied the feeding practices of parents of children with ‘avid’ eating traits, which can lead to obesity
Focusing on health or deciding when it is time for a meal or snack helps parents to use supportive feeding practices.
Supportive feeding practices could include involving children in decisions about food, or sitting together for mealtimes
New research from Aston University has shone a light on the best ways for parents to encourage healthy eating in their children.
The team of academics from Aston University’s School of Psychology, led by Professor Jacqueline Blissett, with Dr Katie Edwards as the lead researcher, looked at the meal- and snack-time practices of parents of children with ‘avid’ eating behaviours. ‘Avid’ eaters, who make up around 20% of children, particularly love food, are often hungry and will eat in response to food cues in the environment and their emotions, not just when they are hungry. They are the most susceptible to obesity and therefore encouraging a healthy, balanced diet is vital.
Feeding children with avid eating behaviours can be challenging and the researchers wanted to understand how factors in everyday life, such as parent mood or eating situations, influence the feeding practices that parents use. Understanding this can help to create better support for families around meal and snack times and reduce the risk of children developing obesity.
Dr Edwards says that the research shows that when parents prioritise children’s health or decide when it is time for a meal or snack, parents are more likely to use supportive feeding practices which create structure around meal or snack times or encourage children to be independent with their food choices. For example, parents could sit and eat with their children, choose what food is available for their children, or involve children in decisions about what food to eat.
She adds that there are three main things that parents can do to help encourage healthy eating behaviour. The first is to focus on health, by providing nutritious and balanced meals. The second is to ensure a calm and positive atmosphere during eating occasions. The final recommendation is that parents should take the lead on setting meal- and snack-times, with a good structure being three meals and two snacks a day. These recommendations are linked to parents’ use of supportive feeding practices which are known to encourage children’s healthy eating.
To carry out the research, the team recruited parents of children aged 3-5 with avid eating behaviour and asked them to download an app to their smartphones. The app sent four semi-random reminders per day for a 10-day period, asking them to complete a survey with information about mood and stress levels. Every time a child had a meal or a snack, or asked for food, parents completed another survey to give information about feeding practices (including those which give children structure, or independence, around food), mealtime goals (such as prioritising healthy eating), and information about the mealtime setting (such as the atmosphere).
Previous research from this team at Aston University identified four main eating traits in children. As well as ‘avid’, the other traits, not studied here, are ‘typical’ eaters, who have no extreme behaviours, ‘avoidant’ eaters, who are extremely fussy, and ‘emotional’ eaters, who eat in response to emotions but do not necessarily enjoy food in the way that avid eaters do.
“Given the challenges that parents may face and the risk of childhood obesity, we will use these findings to develop feeding support for families. Encouraging parents to use feeding practices which provide structure around meal and snack times, or promote children’s independence with food, could be helpful for supporting children’s healthy eating.
Parental use of structure-based and autonomy support feeding practices with children with avid eating behaviour: an Ecological Momentary Assessment study
Invention improves ‘gene gun,’ targets efficiency gains in plant research
Iowa State engineers, left to right, Connor Thorpe and Shan Jiang helped invent the "Flow Guiding Barrel," which improves gene gun performance for the genetic modification of plants. Jiang is holding a Flow Guiding Barrel. A gene gun is on the left.
Credit: Photo by Ryan Riley/Iowa State University College of Engineering
AMES, Iowa – Plant scientists have used a standard “gene gun” since 1988 to genetically modify crops for better yield, nutrition, pest resistance and other valuable traits.
That technology, which loads genetic materials on tiny particles and uses high pressure to shoot them into plant cells, has presented challenges to plant scientists, including inefficiency, inconsistency and even tissue damage caused by high-velocity particles.
But that was just the way these experiments worked, and plant scientists worked around the challenges.
“We didn’t even know we had a problem,” said Kan Wang, an Iowa State University agronomist and Charles F. Curtiss Distinguished Professor in Agriculture and Life Sciences.
Shan Jiang, an Iowa State associate professor of materials science and engineering, wondered if his research group could do something to improve that basic tool of plant research. Ultimately, he and the group determined plant scientists had been “shooting a bullet without a barrel” for 40 years.
A paper just published by the journal Nature Communications details the research team’s search for a solution, its subsequent findings and the invention that launched a startup company.
The project was more than solving a single engineering problem, though. Jiang, because of his research resume, really wanted to use his engineering approach to improve plant science and, potentially, human lives.
Post-doc lessons
After earning his doctorate from the University of Illinois Urbana-Champaign, Jiang went to work as a post-doctoral researcher in the Langer Lab at the Massachusetts Institute of Technology.
That’s the lab of Robert Langer, once called the “smartest man in Boston” by the Boston Globe and co-founder and, until last August, a board member for Moderna, Inc., a leader in the creation of mRNA medicine, including vaccines for COVID-19.
Jiang was one of 15 post-docs working on new ideas to deliver genetic materials for medical therapies.
“It was such difficult research,” he said.
But one outcome, even after research funding dried up, was the use of messenger RNA to produce proteins that could help the body fight off disease.
“That research had a profound impact in my life,” Jiang said. “When I arrived at Iowa State, I thought about what I wanted to do.”
But there was no research hospital and limited opportunities for medical research.
He looked around in the scientific literature and read about delivering DNA into plant cells to introduce or boost particular traits, including high crop yields, resistance to insects or tolerance of heat.
He picked up the phone and made a cold call.
Wang answered and was surprised to be talking to a materials engineer but was interested enough to schedule a lunch and talk about the challenges of plant science research, particularly the challenge of delivering genetic materials through a plant’s tough cell walls.
“It was such an overlooked area,” Jiang said. “Very few materials scientists were working on plant cell delivery. Agriculture is always overlooked – people want to cure cancer.”
From losing patience to a shock discovery
The decades-old “gene gun” used by plant scientists for what’s known as “biolistic” delivery of genetic information works by coating gold or tungsten microparticles, just a few millionths of a meter in size, with genetic material and then shooting particle and cargo into plant cells.
Some of those cells survive the particle bombardment, take up the introduced DNA and express the corresponding traits. Whole plants can then be grown from the transformed cells.
“However, biolistic delivery faces notable challenges with efficiency, consistency, and tissue damage caused by high-velocity microprojectiles, which hinder regeneration and transformation,” Jiang and co-authors wrote in their paper about the project (see team and paper details below). “Additionally, it often leads to fragmented and multiple transgene insertions in the genome, resulting in unpredictable gene expression.”
Jiang and his research collaborators began looking for solutions – “We tried to minimize the error bar,” he said.
The researchers tried everything they could think of, but Jiang said they made little progress. After four years, it was time to reconsider the time and effort spent on the project.
“We were losing hope and patience,” Jiang said.
In one last push for a solution, the research team ran computational fluid dynamics models of gene gun particle flows and discovered a bottleneck within an internal barrel. It seemed too narrow and restrictive, leading to particle loss, disrupted flow, decreased pressures, slower speeds, and uneven distribution at the target cells.
“These findings pinpoint critical limitations in the gene gun design and led us to hypothesize that engineering the flow dynamics within the gene gun could significantly improve its efficiency and consistency,” Jiang and his collaborators wrote.
To do that, the researchers designed a new internal barrel for the gene gun – they call it a “Flow Guiding Barrel” – and Connor Thorpe, a doctoral student and 3D-printing hobbyist, printed one for testing.
“It improved performance by 50%, then two, three, five, ten, twenty times,” Jiang said. “I was very shocked, to be honest with you.”
Easier plant transformations
The computer modeling shows a conventional gene gun directs about 21% of loaded particles toward its plant cell targets while a gene gun modified with the Flow Guiding Barrel delivers nearly 100%.
Subsequent tests by plant scientists found, for example, a 22-fold increase in transient transfection efficiency in tests with onions, a 17-fold improvement in viral infection efficiency in maize seedlings and double the efficiency of experiments using CRISPR genome editing tools in wheat.
“No previous device has achieved such improvements, offering substantial potential for advancing genotype independent transformation and genome editing for plants,” paper co-authors wrote.
Wang, the Iowa State plant scientist originally approached by Jiang, noted laboratory “improvements of 10-fold and sometimes 20-fold. We’re able to work far more efficiently.”
Yiping Qi, a professor of plant science and landscape architecture at the University of Maryland and a project collaborator, said the Flow Guiding Barrel “will make plant transformation and genome editing easier with improved efficiency.”
In one test, for example, he said the Flow Guiding Barrel allowed CRISPR reagents to penetrate deeper into the shoot apical meristem of bread wheat, the part of the plant where cell and leaf production occur.
“This translated to the higher efficiency of heritable genome editing in the next generation of wheat,” Qi said. “While this demonstration was done in wheat, one can envision such improvement can also benefit other crops, like barley, sorghum, etc.”
Support for research and development of the Flow Guiding Barrel came from Iowa State sources, including the Digital and Precision Agriculture Research and Innovation Platform; The Agriculture and Food Research Initiative of the U.S. Department of Agriculture’s National Institute of Food and Agriculture; the National Science Foundation; and the Department of Energy.
A startup for plant science
The Flow Guiding Barrel worked so well, Jiang; Thorpe; Wang; Kyle Miller, a former doctoral student in Jiang’s lab; and Alan Eggenberger, an Iowa State research scientist in materials science and engineering; took steps to investigate the commercial potential of the invention. Jiang and Thorpe also enrolled in Iowa State’s startup programs and later co-founded a company with Jibing Lin, an Iowa State graduate and startup leader. The U.S. Department of Energy’s Small Business Technology Transfer program has supported the company’s development.
“This project would not be possible without close collaboration with plant biologists,” Jiang said. “We believe the best way to give back is to make our tools commercially available so they can be broadly used in the plant science community.”
The Iowa State University Research Foundation filed for patent protection on the innovation and has licensed the commercial rights to the co-founders’ company, Hermes Biomaterials Inc. The company is based at the Iowa State University Research Park and is manufacturing its products in Iowa. The company continues its customer discovery work based on the National Science Foundation’s Innovation Corps program and has started selling products.
With efficiency gains of 10- and 20-fold, Jiang said the Flow Guiding Barrel could save plant scientists and agriculture companies millions of dollars in time and plant or product turnaround.
“This is a small device, and it seems overly simple,” Jiang said. “But the benefits it can bring are invaluable. It enables the development of safer and more effective strategies to improve crops that can better withstand environmental changes, enhance nutritional content, and contribute to sustainable energy production.”
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The research team
Iowa State University Materials Science and Engineering: Shan Jiang, Connor Thorpe, Alan Eggenberger, Ritinder Sandhu
Iowa State Agronomy and Crop Bioengineering Center: Kan Wang, Qing Ji, Keunsub Lee, Steven Whitham
Iowa State Plant Pathology, Entomology and Microbiology: Aline Chicowski, Weihui Xu
University of Maryland Plant Science and Landscape Architecture: Yiping Qi, Weifeng Luo
Read the paper
“Enhancing biolistic plant transformation and genome editing with a flow guiding barrel,” Nature Communications, July 1, 2025, https://doi.org/10.1038/s41467-025-60761-x
Earth’s carbon-climate system may be more fragile than widely thought, according to a new IIASA-led study that looks at the planet’s response to human pressures from a planetary perspective.
In their paper published in Science of the Total Environment, researchers from IIASA and Lviv Polytechnic National University in Ukraine, presented a novel approach to measure and understand human pressure on planet Earth. The researchers explored how carbon emissions can be translated into measures of “stress” and “strain” to derive new insights into how the planet is changing.
“Until now, the scientific community has mainly measured Earth’s condition in gigatons of carbon per year. That’s important, but it doesn’t show how Earth as a physical system responds to the growing pressure we’re putting on it,” explains lead author Matthias Jonas, a researcher in the IIASA Advancing Systems Analysis Program. “We wanted to see how the entire Earth system stretches and strains under that burden.”
One of their key findings is the quantification of “stress power”, which is the rate at which humans are adding energy per volume to Earth’s system. In 2021, this stress power reached between 12.8 and 15.5 pascals per year. While this pressure may sound small (it is similar to the gentle push of a light breeze), spread over the entire atmosphere, land, and oceans, it is enough to signal that Earth’s system might be pushed outside its natural balance. For comparison, both strain and stress power center around zero for a balanced Earth not exposed to human-induced global warming.
The researchers also analyzed changes over time in Earth’s “delay time”, which describes how quickly the planet’s carbon system reacts to stress and identified a turning point between 1925 and 1945, suggesting that Earth’s system began shifting its response to stress much earlier than previously believed.
“This early turning point was unexpected,” says Jonas. “It suggests that Earth’s land and oceans may have started changing from their usual patterns as early as the first half of the 20th century. After that, instead of working as they used to, these systems were increasingly overwhelmed by human activities and eventually stopped absorbing CO₂ as effectively.”
This could mean countries need to act sooner than planned to cut greenhouse gas emissions.
“Meeting future emissions targets is important, but we also need to pay attention to how quickly Earth is becoming more fragile,” Jonas says. “Even if we hit our targets, the weakening of Earth’s natural systems could still leave us facing major disruptions sooner than expected. Earth’s shift to earlier fragility isn’t captured in climate models yet, but it needs to be.”
The team emphasizes the need for further research to quantify this shift and include their stress-strain approach in global climate modeling. They hope that by expanding how scientists track Earth’s condition from counting carbon alone to understanding how the planet physically reacts under pressure, the world can better prepare for the challenges ahead.
Reference: Jonas, M., Bun, R., Ryzha, I., & Żebrowski, P. (2025). Human-induced carbon stress power upon Earth: Integrated data set, rheological findings and consequences. Science of the Total Environment DOI: 10.1016/j.scitotenv.2025.179922
About IIASA: The International Institute for Applied Systems Analysis (IIASA) is an international scientific institute that conducts research into the critical issues of global environmental, economic, technological, and social change that we face in the twenty-first century. Our findings provide valuable options to policymakers to shape the future of our changing world. IIASA is independent and funded by prestigious research funding agencies in Africa, the Americas, Asia, and Europe. www.iiasa.ac.at
CHAMPAIGN, Ill. — By combining artificial intelligence with automated robotics and synthetic biology, researchers at the University of Illinois Urbana-Champaign have dramatically improved performance of two important industrial enzymes — and created a user-friendly, fast process to improve many more.
“Enzymes have been increasingly used in energy production, in therapeutics, even in consumer products like laundry detergent. But they are not as widely used as they could be, because they still have limitations. Our technology can help address those limitations efficiently,” said Zhao, who also is affiliated with the Carl R. Woese Institute for Genomic Biology at the U. of I.
Enzymes are proteins that carry out specific catalytic functions that drive many biological processes. Those seeking to harness enzymes to advance medicine, technology, energy or sustainability often run into roadblocks involving an enzyme’s efficiency or its ability to single out a desired target amidst a complex chemical environment, Zhao said.
“Improving protein function, particularly enzyme function, is challenging because we don’t know exactly what kinds of mutations we should introduce — and it’s usually not just a single mutation; it’s a lot of synergistic mutations,” Zhao said. “With our model of integrating AI and automated synthetic biology, we offer an efficient way to solve that problem.”
Zhao’s group previously reported an AI model to predict an enzyme’s function based on its sequence. In the new paper, the researchers take their AI a step farther: predicting what changes to a known protein would improve its function.
“In a typically sized enzyme, the possible number of variations is larger than the number of atoms in the universe,” said Nilmani Singh, the co-first author of the paper. “So we use the AI method to help us create a relatively small library of potentially useful variant combinations, instead of randomly searching the whole protein sequence.”
However, training and improving an AI model is more than just code; it requires a lot of input, data and feedback. So the Illinois team coupled their AI models with the automated capabilities offered by the iBioFoundry, a center at the U. of I. dedicated to quick, user-friendly engineering and testing of biological systems ranging from enzymes to whole cells. Zhao directs the iBioFoundry, which is supported by the National Science Foundation.
In the new paper, the researchers lay out their process: First, they ask the AI tool how to improve a desired enzyme’s performance. The AI tool searches datasets of known enzyme structures and suggests sequence changes. The automated protein-building machines at the iBioFoundry produce the suggested enzymes, which are then rapidly tested to characterize their functions. The data from those tests are fed into another AI model, which uses the information to improve the next round of suggested protein designs.
“It’s a step toward a self-driving lab: a lab that designs its own proteins, makes the proteins, tests them and makes the next one,” said Stephan Lane, the manager of the iBioFoundry and co-first author. “The designing and learning is done by an AI algorithm, and the building and testing is done by robotics.”
Using this method, the team produced variants of two key industrial enzymes with substantially improved performance. One enzyme, added to animal feed to improve its nutritional content, increased its activity by 26 times. The other, a catalyst used in industrial chemical synthesis, had 16 times greater activity and 90 times greater substrate preference, meaning it was far less likely to grab molecules that were not its target.
“We described two enzymes in the paper, but it’s truly a generalized approach. We only need a protein sequence and an assay,” Zhao said. “We want to try to apply it to as many enzymes as possible.”
Next, the researchers plan to continue improving their AI models and upgrade equipment for even faster, higher-throughput synthesis and testing. They also have developed a user interface, enabling the system to run with a simple typed query. Their aim is to offer their method as a service for other researchers seeking to improve enzymes and speed drug development and innovations in energy and technology.
“For the user interface, the motivation is to allow people with different backgrounds to use the tool,” said graduate student Tianhao Yu, a coauthor of the paper. “If an experimental scientist doesn’t know how to run Python programs, then they can use our interface to help them run the program. They just need to use English to describe their needs, and it will automatically run.”
The National Science Foundation and the U.S. Department of Energy supported this work.
Editor's note: To reach Huimin Zhao, email zhao5@illinois.edu. The paper “A generalized platform for artificial intelligence-powered autonomous enzyme engineering” is available online. DOI: 10.1038/s41467-025-61209-y
