In the past two years, the region has more than doubled its annual spending on stormwater drainage.

Germany said the European Commission’s emissions proposal should be discussed by leaders at their October meeting.

South Africa’s environment minister is expressing dismay over developed nations reneging on funding pledges.

Alan Lightman has spent much of his authorial career writing about scientific discovery, the boundaries of knowledge, and remarkable findings from the world of research. His latest book “The Shape of Wonder,” co-authored with the lauded English astrophysicist Martin Rees and published this month by Penguin Random House, offers both profiles of scientists and an examination of scientific methods, humanizing researchers and making an affirmative case for the value of their work. Lightman is a professor of the practice of the humanities in MIT’s Comparative Media Studies/Writing Program; Rees is a fellow of Trinity College at Cambridge University and the UK’s Astronomer Royal. Lightman talked with MIT News about the new volume.

Q: What is your new book about?

A: The book tries to show who scientists are and how they think. Martin and I wrote it to address several problems. One is mistrust in scientists and their institutions, which is a worldwide problem. We saw this problem illustrated during the pandemic. That mistrust I think is associated with a belief by some people that scientists and their institutions are part of the elite establishment, a belief that is one feature of the populist movement worldwide. In recent years there’s been considerable misinformation about science. And, many people don’t know who scientists are.

Another thing, which is very important, is a lack of understanding about evidence-based critical thinking. When scientists get new data and information, their theories and recommendations change. But this process, part of the scientific method, is not well-understood outside of science. Those are issues we address in the book. We have profiles of a number of scientists and show them as real people, most of whom work for the benefit of society or out of intellectual curiosity, rather than being driven by political or financial interests. We try to humanize scientists while showing how they think.

Q: You profile some well-known figures in the book, as well as some lesser-known scientists. Who are some of the people you feature in it?

A: One person is a young neuroscientist, Lace Riggs, who works at the McGovern Institute for Brain Research at MIT. She grew up in difficult circumstances in southern California, decided to go into science, got a PhD in neuroscience, and works as a postdoc researching the effect of different compounds on the brain and how that might lead to drugs to combat certain mental illnesses. Another very interesting person is Magdalena Lenda, an ecologist in Poland. When she was growing up, her father sold fish for a living, and took her out in the countryside and would identify plants, which got her interested in ecology. She works on stopping invasive species. The intention is to talk about people’s lives and interests, and show them as full people.

While humanizing scientists in the book, we show how critical thinking works in science. By the way, critical thinking is not owned by scientists. Accountants, doctors, and many others use critical thinking. I’ve talked to my car mechanic about what kinds of problems come into the shop. People don’t know what causes the check engine light to go on — the catalytic converter, corroded spark plugs, etc. — so mechanics often start from the simplest and cheapest possibilities and go to the next potential problem, down the list. That’s a perfect example of critical thinking. In science, it is checking your ideas and hypotheses against data, then updating them if needed.

Q: Are there common threads linking together the many scientists you feature in the book?

A: There are common threads, but also no single scientific stereotype. There’s a wide range of personalities in the sciences. But one common thread is that all the scientists I know are passionate about what they’re doing. They’re working for the benefit of society, and out of sheer intellectual curiosity. That links all the people in the book, as well as other scientists I’ve known. I wish more people in America would realize this: Scientists are working for their overall benefit. Science is a great success story. Thanks to scientific advances, since 1900 the expected lifespan in the U.S, has increased from a little more than 45 years to almost 80 years, in just a century, largely due to our ability to combat diseases. What’s more vital than your lifespan?

This book is just a drop in the bucket in terms of what needs to be done. But we all do what we can. 

This is a current list of where and when I am scheduled to speak:

• I’m speaking and signing books at the Cambridge Public Library on October 22, 2025 at 6 PM ET. The event is sponsored by Harvard Bookstore.
• I’m giving a virtual talk about my book Rewiring Democracy at 1 PM ET on October 23, 2025. The event is hosted by Data & Society. More details to come.
• I’m speaking at the World Forum for Democracy in Strasbourg, France, November 5-7, 2025.
• I’m speaking and signing books at the University of Toronto Bookstore in Toronto, Ontario, Canada on November 14, 2025. Details to come...

Research:

Nondestructive detection of multiple dried squid qualities by hyperspectral imaging combined with 1D-KAN-CNN

Abstract: Given that dried squid is a highly regarded marine product in Oriental countries, the global food industry requires a swift and noninvasive quality assessment of this product. The current study therefore uses visible­near-infrared (VIS-NIR) hyperspectral imaging and deep learning (DL) methodologies. We acquired and preprocessed VIS-NIR (400­1000 nm) hyperspectral reflectance images of 93 dried squid samples. Important wavelengths were selected using competitive adaptive reweighted sampling, principal component analysis, and the successive projections algorithm. Based on a Kolmogorov-Arnold network (KAN), we introduce a one-dimensional, KAN convolutional neural network (1D-KAN-CNN) for nondestructive measurements of fat, protein, and total volatile basic nitrogen…...

Interesting analysis:

When cyber incidents occur, victims should be notified in a timely manner so they have the opportunity to assess and remediate any harm. However, providing notifications has proven a challenge across industry.

When making notifications, companies often do not know the true identity of victims and may only have a single email address through which to provide the notification. Victims often do not trust these notifications, as cyber criminals often use the pretext of an account compromise as a phishing lure.

[…]

This report explores the challenges associated with developing the native-notification concept and lays out a roadmap for overcoming them. It also examines other opportunities for more narrow changes that could both increase the likelihood that victims will both receive and trust notifications and be able to access support resources...

Each year, the U.S. energy industry loses an estimated 3 percent of its natural gas production, valued at $1 billion in revenue, to leaky infrastructure. Escaping invisibly into the air, these methane gas plumes can now be detected, imaged, and measured using a specialized lidar flown on small aircraft.

This lidar is a product of Bridger Photonics, a leading methane-sensing company based in Bozeman, Montana. MIT Lincoln Laboratory developed the lidar's optical-power amplifier, a key component of the system, by advancing its existing slab-coupled optical waveguide amplifier (SCOWA) technology. The methane-detecting lidar is 10 to 50 times more capable than other airborne remote sensors on the market.

"This drone-capable sensor for imaging methane is a great example of Lincoln Laboratory technology at work, matched with an impactful commercial application," says Paul Juodawlkis, who pioneered the SCOWA technology with Jason Plant in the Advanced Technology Division and collaborated with Bridger Photonics to enable its commercial application.

Today, the product is being adopted widely, including by nine of the top 10 natural gas producers in the United States. "Keeping gas in the pipe is good for everyone — it helps companies bring the gas to market, improves safety, and protects the outdoors," says Pete Roos, founder and chief innovation officer at Bridger. "The challenge with methane is that you can't see it. We solved a fundamental problem with Lincoln Laboratory."

A laser source "miracle"

In 2014, the Advanced Research Projects Agency-Energy (ARPA-E) was seeking a cost-effective and precise way to detect methane leaks. Highly flammable and a potent pollutant, methane gas (the primary constituent of natural gas) moves through the country via a vast and intricate pipeline network. Bridger submitted a research proposal in response to ARPA-E's call and was awarded funding to develop a small, sensitive aerial lidar.

Aerial lidar sends laser light down to the ground and measures the light that reflects back to the sensor. Such lidar is often used for producing detailed topography maps. Bridger's idea was to merge topography mapping with gas measurements. Methane absorbs light at the infrared wavelength of 1.65 microns. Operating a laser at that wavelength could allow a lidar to sense the invisible plumes and measure leak rates.

"This laser source was one of the hardest parts to get right. It's a key element," Roos says. His team needed a laser source with specific characteristics to emit powerfully enough at a wavelength of 1.65 microns to work from useful altitudes. Roos recalled the ARPA-E program manager saying they needed a "miracle" to pull it off.

Through mutual connections, Bridger was introduced to a Lincoln Laboratory technology for optically amplifying laser signals: the SCOWA. When Bridger contacted Juodawlkis and Plant, they had been working on SCOWAs for a decade. Although they had never investigated SCOWAs at 1.65 microns, they thought that the fundamental technology could be extended to operate at that wavelength. Lincoln Laboratory received ARPA-E funding to develop 1.65-micron SCOWAs and provide prototype units to Bridger for incorporation into their gas-mapping lidar systems.

"That was the miracle we needed," Roos says.

A legacy in laser innovation

Lincoln Laboratory has long been a leader in semiconductor laser and optical emitter technology. In 1962, the laboratory was among the first to demonstrate the diode laser, which is now the most widespread laser used globally. Several spinout companies, such as Lasertron and TeraDiode, have commercialized innovations stemming from the laboratory's laser research, including those for fiber-optic telecommunications and metal-cutting applications.

In the early 2000s, Juodawlkis, Plant, and others at the laboratory recognized a need for a stable, powerful, and bright single-mode semiconductor optical amplifier, which could enhance lidar and optical communications. They developed the SCOWA (slab-coupled optical waveguide amplifier) concept by extending earlier work on slab-coupled optical waveguide lasers (SCOWLs). The initial SCOWA was funded under the laboratory's internal technology investment portfolio, a pool of R&D funding provided by the undersecretary of defense for research and engineering to seed new technology ideas. These ideas often mature into sponsored programs or lead to commercialized technology.

"Soon, we developed a semiconductor optical amplifier that was 10 times better than anything that had ever been demonstrated before," Plant says. Like other semiconductor optical amplifiers, the SCOWA guides laser light through semiconductor material. This process increases optical power as the laser light interacts with electrons, causing them to shed photons at the same wavelength as the input laser. The SCOWA's unique light-guiding design enables it to reach much higher output powers, creating a powerful and efficient beam. They demonstrated SCOWAs at various wavelengths and applied the technology to projects for the Department of Defense.

When Bridger Photonics reached out to Lincoln Laboratory, the most impactful application of the device yet emerged. Working iteratively through the ARPA-E funding and a Cooperative Research and Development Agreement (CRADA), the team increased Bridger's laser power by more than tenfold. This power boost enabled them to extend the range of the lidar to elevations over 1,000 feet.

"Lincoln Laboratory had the knowledge of what goes on inside the optical amplifier — they could take our input, adjust the recipe, and make a device that worked very well for us," Roos says.

The Gas Mapping Lidar was commercially released in 2019. That same year, the product won an R&D 100 Award, recognizing it as a revolutionary advancement in the marketplace.

A technology transfer takes off

Today, the United States is the world's largest natural gas supplier, driving growth in the methane-sensing market. Bridger Photonics deploys its Gas Mapping Lidar for customers nationwide, attaching the sensor to planes and drones and pinpointing leaks across the entire supply chain, from where gas is extracted, piped through the country, and delivered to businesses and homes. Customers buy the data from these scans to efficiently locate and repair leaks in their gas infrastructure. In January 2025, the Environmental Protection Agency provided regulatory approval for the technology.

According to Bruce Niemeyer, president of Chevron's shale and tight operations, the lidar capability has been game-changing: "Our goal is simple — keep methane in the pipe. This technology helps us assure we are doing that … It can find leaks that are 10 times smaller than other commercial providers are capable of spotting."

At Lincoln Laboratory, researchers continue to innovate new devices in the national interest. The SCOWA is one of many technologies in the toolkit of the laboratory's Microsystems Prototyping Foundry, which will soon be expanded to include a new Compound Semiconductor Laboratory – Microsystem Integration Facility. Government, industry, and academia can access these facilities through government-funded projects, CRADAs, test agreements, and other mechanisms.

At the direction of the U.S. government, the laboratory is also seeking industry transfer partners for a technology that couples SCOWA with a photonic integrated circuit platform. Such a platform could advance quantum computing and sensing, among other applications.

"Lincoln Laboratory is a national resource for semiconductor optical emitter technology," Juodawlkis says.

A new MIT initiative known as Day of Design offers free, open-source, hands-on design activities for all classrooms, in addition to professional development opportunities and signature events. The material engages pK-12 learners in the skills they need to solve complex open-ended problems while also considering user, social, and environmental needs. Inspired by Day of AI and Day of Climate, it is a new collaborative effort by the MIT Morningside Academy for Design (MAD) and the WPS Institute, with support from the MIT pK-12 Initiative.

“At MIT, design is practiced across departments — from the more obvious ones, like architecture and mechanical engineering, to less apparent ones, like biology and chemistry. Design skills support students in becoming strong collaborators, idea-makers, and human-centered problem-solvers. The Day of Design initiative seeks to share these skills with the K-12 audience through bite-sized, engaging activities for every classroom,” says Rosa Weinberg, who co-led the development of Day of Design and serves as MAD’s K–12 design education lead.

These interdisciplinary resources are designed collaboratively with feedback from teachers and grounded in exciting themes across science, humanities, art, engineering, and other subject areas, serving educators and learners regardless of their experience with design and making. Activities are scaffolded like “grammar lessons” for design education, including classroom-ready slides, handouts, tutorial videos, and facilitation tips supporting 21st century mindsets. All materials will be shared online, enabling educators to use the content as-is, or modify it as needed for their classrooms and other informal learning settings.

Rachel Adams, a former teacher and head of teaching and learning at the WPS Institute, explains, “There can be a gap between open-ended teaching materials and what teachers actually need in their classrooms. Day of Design classroom materials are piloted and workshopped by an interdisciplinary cohort of teachers who make up our Teacher Innovation Fellowship. This collaborative design process allows us to bridge the gap between cutting-edge MIT research with practical student-centered design lessons. These materials represent a new way of thinking that honors both the innovation happening in the labs at MIT and the real-world needs of educators.” 

Day of Design also features signature events and a yearly, real-world challenge that brings all the design skills together. It is intended for educators who want ready-to-use design and making activities that connect to their subject areas and mindsets, and for students eager to develop problem-solving skills, creativity, and hands-on experience. Schools and districts looking to engage learners through interdisciplinary, project-based approaches can adopt the program as a flexible framework, while community partners can use it to provide young people with tools and spaces to create.

Cedric Jacobson, a chemistry teacher at Brooke High School in Boston who participated in MAD’s Teacher Innovation Fellowship and contributed to testing the Day of Design curriculum, emphasizes it “provides opportunities for teachers to practice and interact with design principles in concrete ways through multiple lesson structures. This process empowers them to try design principles in model lessons before preparing to use them in their own curriculum.”

Evan Milstein-Greengart, another Teacher Innovation Fellow, describes how “having this hands-on experience changed the way I thought about education. I felt like a kid again — going back to playground learning — and I want to bring that same spirit into my classroom.” 

Closing the skills gap through design education

Technologies such as artificial intelligence, robotics, and biotech are reshaping work and society. The World Economic Forum estimates that 39 percent of key job skills will change by 2030. At the same time, research shows student engagement drops sharply in high school, with a third of students experiencing what is often called the “engagement cliff.” Many do not encounter design until college, if at all.

There is a growing need to foster not just technical literacy, but design fluency — the ability to approach complex problems with empathy, creativity, and critical thinking. Design education helps students prototype solutions, iterate based on feedback, and communicate ideas clearly. Studies have shown it can improve creative thinking, motivation, problem-solving, self-efficacy, and academic achievement.

At MIT, design is a way of thinking and creating that spans disciplines — from bioengineering and architecture to mechanical systems and public policy. It is both creative and analytical, grounded in iteration, user input, and systems thinking. Day of Design reflects MIT’s “mens et manus” (“mind and hand”) motto and extends the tools of design to young learners and educators.

“The workshops help students develop skills that can be applied across multiple subject areas, using topics that draw context from MIT research while remaining exciting and accessible to middle and high school students,” explains Weinberg. “For example, ‘Cosmic Comfort,’ one of our pilot workshops, was inspired by MIT's Space Architecture course (MAS.S66/4.154/16.89). It challenges students to consider how you might make a lunar habitat feel like home, while focusing on developing the crucial design skill of ideation — the ability to generate multiple creative solutions.”

Building on an MIT legacy

Day of Design builds on the model of Day of AI and Day of Climate, two ongoing efforts by MIT RAISE and the MIT pK-12 Initiative. All three initiatives share free, open-source activities, professional development materials, and events that connect MIT research with educators and students worldwide. Since 2021, Day of AI has reached more than 42,000 teachers and 1.5 million students in 170 countries and all 50 U.S. states. Day of Climate, launched in March 2025, has already recorded over 50,000 website visitors, 300 downloads of professional development materials, and an April launch event at the MIT Museum that drew 200 participants.

“Day of Design builds on the spirit of Day of AI and Day of Climate by inviting young people to engage with real-world challenges through creative work, meaningful collaboration, and deep empathy for others. These initiatives reflect MIT’s commitment to hands-on, transdisciplinary learning, empowering future young leaders not just to understand the world, but to shape it,” says Claudia Urrea, executive director for the pK–12 Initiative at MIT Open Learning. 

Kicking off with connection

“Learning and creating together in person sparks the kind of ideas and connections that are hard to make any other way. Collective learning helps everyone think bigger and more creatively, while building a more deeply connected community that keeps that growth alive,” observes Caitlin Morris, PhD student in Fluid Interfaces, a 2024 MAD Design Fellow, and co-organizer of Day of Design: Connect, which will kick off Day of Design on Sept. 25. 

Following the launch, the first set of classroom resources will be introduced during the 2025–26 school year, starting with activities for grades 7–12. Additional resources for younger learners, along with training opportunities for educators, will be added over time. Each year, new design skills and mindsets will be incorporated, creating a growing library of activities. While initial events will take place at MIT, organizers plan to expand programming globally.

Teacher Innovation Fellow Jessica Toupin, who piloted Day of Design activities in her math classroom, reflects on the impact: “As a math teacher, I don’t always get to focus on design. This material reminded me of the joy of learning — and when I brought it into my classroom, students who had struggled came alive. Just the ability to play and build showed me they were capable of so much more.”

The head of the National Weather Service has long sought to embed forecasters in emergency operation centers nationwide.

Mayoral candidates of both parties say the city needs to shake up its climate programs.

Environmental justice groups were riding momentum against the industry, but then refinery closure announcements changed everything.

The lawsuit by Puerto Rico alleged that oil companies violated RICO statutes after Hurricane Maria killed 3,000 people in 2017.

The state Legislature will vote Saturday on renewing its cap-and-trade program through 2045, which could lead to linking with Washington state’s program.

The U.K. boss of the Heartland Institute said she had been influencing Reform UK “at the highest level.”

A number of moonshot solutions to cool the planet have gained traction in recent years amid faltering efforts to stem climate change by cutting emissions.

The shake-up is due to be completed by the time of the IMF and World Bank’s mid-October meetings.

The EU is currently trying to simplify its sustainable finance framework.

Ever since freezers were invented, the life sciences industry has been reliant on them. That’s because many patient samples, drug candidates, and other biologics must be stored and transported in powerful freezers or surrounded by dry ice to remain stable.

The problem was on full display during the Covid-19 pandemic, when truckloads of vaccines had to be discarded because they had thawed during transport. Today, the stakes are even higher. Precision medicine, from CAR-T cell therapies to tumor DNA sequencing that guides cancer treatment, depends on pristine biological samples. Yet a single power outage, shipping delay, or equipment failure can destroy irreplaceable patient samples, setting back treatment by weeks or halting it entirely. In remote areas and developing nations, the lack of reliable cold storage effectively locks out entire populations from these life-saving advances.

Cache DNA wants to set the industry free from freezers. At MIT, the company’s founders created a new way to store and preserve DNA molecules at room temperature. Now the company is building biomolecule preservation technologies that can be used in applications across health care, from routine blood tests and cancer screening to rare disease research and pandemic preparedness.

“We want to challenge the paradigm,” says Cache DNA co-founder and former MIT postdoc James Banal. “Biotech has been reliant on the cold chain for more than 50 years. Why hasn’t that changed? Meanwhile, the cost of DNA sequencing has plummeted from $3 billion for the first human genome to under $200 today. With DNA sequencing and synthesis becoming so cheap and fast, storage and transport have emerged as the critical bottlenecks. It’s like having a supercomputer that still requires punch cards for data input.”

As the company works to preserve biomolecules beyond DNA and scale the production of its kits, co-founders Banal and MIT Professor Mark Bathe believe their technology has the potential to unlock new health insights by making sample storage accessible to scientists around the world.

“Imagine if every human on Earth could contribute to a global biobank, not just those living near million-dollar freezer facilities,” Banal says. “That’s 8 billion biological stories instead of just a privileged few. The cures we’re missing might be hiding in the biomolecules of someone we’ve never been able to reach.”

From quantum computing to “Jurassic Park”

Banal came to MIT from Australia to work as a postdoc under Bathe, a professor in MIT’s Department of Biological Engineering. Banal primarily studied in the MIT-Harvard Center for Excitonics, through which he collaborated with researchers from across MIT.

“I worked on some really wacky stuff, like DNA nanotechnology and its intersection with quantum computing and artificial photosynthesis,” Banal recalls.

Another project focused on using DNA to store data. While computers store data as 0s and 1s, DNA can store the same information using the nucleotides A, T, G, and C, allowing for extremely dense storage of data: By one estimate, 1 gram of DNA can hold up to 215 petabytes of data.

After three years of work, in 2021, Banal and Bathe created a system that stored DNA-based data in tiny glass particles. They founded Cache DNA the same year, securing the intellectual property by working with MIT’s Technology Licensing Office, applying the technology to storing clinical nucleic acid samples as well as DNA data. Still, the technology was too nascent to be used for most commercial applications at the time.

Professor of chemistry Jeremiah Johnson had a different approach. His research had shown that certain plastics and rubbers could be made recyclable by adding cleavable molecular bonds. Johnson thought Cache DNA’s technology could be faster and more reliable using his amber-like polymers, similar to how researchers in the “Jurassic Park” movie recover ancient dinosaur DNA from a tree’s fossilized amber resin.

“It started basically as a fun conversation along the halls of Building 16,” Banal recalls. “He’d seen my work, and I was aware of the innovations in his lab.”

Banal immediately saw the potential. He was familiar with the burden of the cold chain. For his MIT experiments, he’d store samples in big freezers kept at -80 degrees Celsius. Samples would sometimes get lost in the freezer or be buried in the inevitable ice build-up. Even when they were perfectly preserved, samples could degrade as they thawed.

As part of a collaboration between Cache DNA and MIT, Banal, Johnson, and two researchers in Johnson’s lab developed a polymer that stores DNA at room temperature. In a nod to their inspiration, they demonstrated the approach by encoding DNA sequences with the “Jurassic Park” theme song.

The researchers’ polymers could encompass a material as a liquid and then form a solid, glass-like block when heated. To release the DNA, the researchers could add a molecule called cysteamine and a special detergent. The researchers showed the process could work to store and access all 50,000 base pairs of a human genome without causing damage.

“Real amber is not great at preservation. It’s porous and lets in moisture and air,” Banal says. “What we built is completely different: a dense polymer network that forms an impenetrable barrier around DNA. Think of it like vacuum-sealing, but at the molecular level. The polymer is so hydrophobic that water and enzymes that would normally destroy DNA simply can’t get through.”

As that research was taking shape, Cache DNA was learning that sample storage was a huge problem from hospitals and research labs. In places like Florida and Singapore, researchers said contending with the effects of humidity on samples was another constant headache. Other researchers across the globe wanted to know if the technology would help them collect samples outside of the lab.

“Hospitals told us they were running out of space,” Banal says. “They had to throw samples out, limit sample collection, and as a last-case scenario, they would use a decades-old storage technology that leads to degradation after a short period of time. It became a north star for us to solve those problems.”

A new tool for precision health

Last year, Cache DNA sent out more than 100 of its first alpha DNA preservation kits to researchers around the world.

“We didn’t tell researchers what to use it for, and our minds were blown by the use cases,” Banal says. “Some used it for collecting samples in the field where cold shipping wasn't feasible. Others evaluated for long term archival storage. The applications were different, but the problem was universal: They all needed reliable storage without the constraint of refrigeration.”

Cache DNA has developed an entire suite of preservation technologies that can be optimized for different storage scenarios. The company also recently received a grant from the National Science Foundation to expand its technology to preserve a broader swath of biomolecules, including RNA and proteins, which could yield new insights into health and disease.

“This important innovation helps eliminate the cold chain and has the potential to unlock millions of genetic samples globally for Cache DNA to empower personalized medicine,” Bathe says. “Eliminating the cold chain is half the equation. The other half is scaling from thousands to millions or even billions of nucleic acid samples. Together, this could enable the equivalent of a ‘Google Books’ for nucleic acids stored at room temperature, either for clinical samples in hospital settings and remote regions of the world, or alternatively to facilitate DNA data storage and retrieval at scale.”

“Freezers have dictated where science could happen,” Banal says. “Remove that constraint, and you start to crack open possibilities: island nations studying their unique genetics without samples dying in transit; every rare disease patient worldwide contributing to research, not just those near major hospitals; the 2 billion people without reliable electricity finally joining global health studies. Room-temperature storage isn’t the whole answer, but every cure starts with a sample that survived the journey.”

Researchers at the Antimicrobial Resistance (AMR) interdisciplinary research group of the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have developed a powerful tool capable of scanning thousands of biological samples to detect transfer ribonucleic acid (tRNA) modifications — tiny chemical changes to RNA molecules that help control how cells grow, adapt to stress, and respond to diseases such as cancer and antibiotic‑resistant infections. This tool opens up new possibilities for science, health care, and industry — from accelerating disease research and enabling more precise diagnostics to guiding the development of more effective medical treatments for diseases such as cancer and antibiotic-resistant infections.

For this study, the SMART AMR team worked in collaboration with researchers at MIT, Nanyang Technological University in Singapore, the University of Florida, the University at Albany in New York, and Lodz University of Technology in Poland.

Addressing current limitations in RNA modification profiling

Cancer and infectious diseases are complicated health conditions in which cells are forced to function abnormally by mutations in their genetic material or by instructions from an invading microorganism. The SMART-led research team is among the world’s leaders in understanding how the epitranscriptome — the over 170 different chemical modifications of all forms of RNA — controls growth of normal cells and how cells respond to stressful changes in the environment, such as loss of nutrients or exposure to toxic chemicals. The researchers are also studying how this system is corrupted in cancer or exploited by viruses, bacteria, and parasites in infectious diseases.

Current molecular methods used to study the expansive epitranscriptome and all of the thousands of different types of modified RNA are often slow, labor-intensive, costly, and involve hazardous chemicals, which limits research capacity and speed.

To solve this problem, the SMART team developed a new tool that enables fast, automated profiling of tRNA modifications — molecular changes that regulate how cells survive, adapt to stress, and respond to disease. This capability allows scientists to map cell regulatory networks, discover novel enzymes, and link molecular patterns to disease mechanisms, paving the way for better drug discovery and development, and more accurate disease diagnostics. 

Unlocking the complexity of RNA modifications

SMART’s open-access research, recently published in Nucleic Acids Research and titled “tRNA modification profiling reveals epitranscriptome regulatory networks in Pseudomonas aeruginosa,” shows that the tool has already enabled the discovery of previously unknown RNA-modifying enzymes and the mapping of complex gene regulatory networks. These networks are crucial for cellular adaptation to stress and disease, providing important insights into how RNA modifications control bacterial survival mechanisms. 

Using robotic liquid handlers, researchers extracted tRNA from more than 5,700 genetically modified strains of Pseudomonas aeruginosa, a bacterium that causes infections such as pneumonia, urinary tract infections, bloodstream infections, and wound infections. Samples were enzymatically digested and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), a technique that separates molecules based on their physical properties and identifies them with high precision and sensitivity. 

As part of the study, the process generated over 200,000 data points in a high-resolution approach that revealed new tRNA-modifying enzymes and simplified gene networks controlling how cells respond and adapt to stress. For example, the data revealed that the methylthiotransferase MiaB, one of the enzymes responsible for tRNA modification ms2i6A, was found to be sensitive to the availability of iron and sulfur and to metabolic changes when oxygen is low. Discoveries like this highlight how cells respond to environmental stresses, and could lead to future development of therapies or diagnostics.

SMART’s automated system was specially designed to profile tRNA modifications across thousands of samples rapidly and safely. Unlike traditional methods, this tool integrates robotics to automate sample preparation and analysis, eliminating the need for hazardous chemical handling and reducing costs. This advancement increases safety, throughput, and affordability, enabling routine large-scale use in research and clinical labs.

A faster and automated way to study RNA

As the first system capable of quantitative, system‑wide profiling of tRNA modifications at this scale, the tool provides a unique and comprehensive view of the epitranscriptome — the complete set of RNA chemical modifications within cells. This capability allows researchers to validate hypotheses about RNA modifications, uncover novel biology, and identify promising molecular targets for developing new therapies.

“This pioneering tool marks a transformative advance in decoding the complex language of RNA modifications that regulate cellular responses,” says Professor Peter Dedon, co-lead principal investigator at SMART AMR, professor of biological engineering at MIT, and corresponding author of the paper. “Leveraging AMR’s expertise in mass spectrometry and RNA epitranscriptomics, our research uncovers new methods to detect complex gene networks critical for understanding and treating cancer, as well as antibiotic-resistant infections. By enabling rapid, large-scale analysis, the tool accelerates both fundamental scientific discovery and the development of targeted diagnostics and therapies that will address urgent global health challenges.”

Accelerating research, industry, and health-care applications

This versatile tool has broad applications across scientific research, industry, and health care. It enables large-scale studies of gene regulation, RNA biology, and cellular responses to environmental and therapeutic challenges. The pharmaceutical and biotech industry can harness it for drug discovery and biomarker screening, efficiently evaluating how potential drugs affect RNA modifications and cellular behavior. This aids the development of targeted therapies and personalized medical treatments.

“This is the first tool that can rapidly and quantitatively profile RNA modifications across thousands of samples,” says Jingjing Sun, research scientist at SMART AMR and first author of the paper. “It has not only allowed us to discover new RNA-modifying enzymes and gene networks, but also opens the door to identifying biomarkers and therapeutic targets for diseases such as cancer and antibiotic-resistant infections. For the first time, large-scale epitranscriptomic analysis is practical and accessible.”

Looking ahead: advancing clinical and pharmaceutical applications

Moving forward, SMART AMR plans to expand the tool’s capabilities to analyze RNA modifications in human cells and tissues, moving beyond microbial models to deepen understanding of disease mechanisms in humans. Future efforts will focus on integrating the platform into clinical research to accelerate the discovery of biomarkers and therapeutic targets. The translation of the technology into an epitranscriptome-wide analysis tool that can be used in pharmaceutical and health-care settings will drive the development of more effective and personalized treatments.

The research conducted at SMART is supported by the National Research Foundation Singapore under its Campus for Research Excellence and Technological Enterprise program.