Scientists at the McGovern Institute for Brain Research at MIT and the Broad Institute of MIT and Harvard have re-engineered a compact RNA-guided enzyme they found in bacteria into an efficient, programmable editor of human DNA. 

The protein they created, called NovaIscB, can be adapted to make precise changes to the genetic code, modulate the activity of specific genes, or carry out other editing tasks. Because its small size simplifies delivery to cells, NovaIscB’s developers say it is a promising candidate for developing gene therapies to treat or prevent disease.

The study was led by Feng Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT who is also an investigator at the McGovern Institute and the Howard Hughes Medical Institute, and a core member of the Broad Institute. Zhang and his team reported their open-access work this month in the journal Nature Biotechnology.

NovaIscB is derived from a bacterial DNA cutter that belongs to a family of proteins called IscBs, which Zhang’s lab discovered in 2021. IscBs are a type of OMEGA system, the evolutionary ancestors to Cas9, which is part of the bacterial CRISPR system that Zhang and others have developed into powerful genome-editing tools. Like Cas9, IscB enzymes cut DNA at sites specified by an RNA guide. By reprogramming that guide, researchers can redirect the enzymes to target sequences of their choosing.

IscBs had caught the team’s attention not only because they share key features of CRISPR’s DNA-cutting Cas9, but also because they are a third of its size. That would be an advantage for potential gene therapies: compact tools are easier to deliver to cells, and with a small enzyme, researchers would have more flexibility to tinker, potentially adding new functionalities without creating tools that were too bulky for clinical use.

From their initial studies of IscBs, researchers in Zhang’s lab knew that some members of the family could cut DNA targets in human cells. None of the bacterial proteins worked well enough to be deployed therapeutically, however: the team would have to modify an IscB to ensure it could edit targets in human cells efficiently without disturbing the rest of the genome.

To begin that engineering process, Soumya Kannan, a graduate student in Zhang’s lab who is now a junior fellow at the Harvard Society of Fellows, and postdoc Shiyou Zhu first searched for an IscB that would make good starting point. They tested nearly 400 different IscB enzymes that can be found in bacteria. Ten were capable of editing DNA in human cells.

Even the most active of those would need to be enhanced to make it a useful genome editing tool. The challenge would be increasing the enzyme’s activity, but only at the sequences specified by its RNA guide. If the enzyme became more active, but indiscriminately so, it would cut DNA in unintended places. “The key is to balance the improvement of both activity and specificity at the same time,” explains Zhu.

Zhu notes that bacterial IscBs are directed to their target sequences by relatively short RNA guides, which makes it difficult to restrict the enzyme’s activity to a specific part of the genome. If an IscB could be engineered to accommodate a longer guide, it would be less likely to act on sequences beyond its intended target.

To optimize IscB for human genome editing, the team leveraged information that graduate student Han Altae-Tran, who is now a postdoc at the University of Washington, had learned about the diversity of bacterial IscBs and how they evolved. For instance, the researchers noted that IscBs that worked in human cells included a segment they called REC, which was absent in other IscBs. They suspected the enzyme might need that segment to interact with the DNA in human cells. When they took a closer look at the region, structural modeling suggested that by slightly expanding part of the protein, REC might also enable IscBs to recognize longer RNA guides.

Based on these observations, the team experimented with swapping in parts of REC domains from different IscBs and Cas9s, evaluating how each change impacted the protein’s function. Guided by their understanding of how IscBs and Cas9s interact with both DNA and their RNA guides, the researchers made additional changes, aiming to optimize both efficiency and specificity.

In the end, they generated a protein they called NovaIscB, which was over 100 times more active in human cells than the IscB they had started with, and that had demonstrated good specificity for its targets.

Kannan and Zhu constructed and screened hundreds of new IscBs before arriving at NovaIscB — and every change they made to the original protein was strategic. Their efforts were guided by their team’s knowledge of IscBs’s natural evolution, as well as predictions of how each alteration would impact the protein’s structure, made using an artificial intelligence tool called AlphaFold2. Compared to traditional methods of introducing random changes into a protein and screening for their effects, this rational engineering approach greatly accelerated the team’s ability to identify a protein with the features they were looking for.

The team demonstrated that NovaIscB is a good scaffold for a variety of genome editing tools. “It biochemically functions very similarly to Cas9, and that makes it easy to port over tools that were already optimized with the Cas9 scaffold,” Kannan says. With different modifications, the researchers used NovaIscB to replace specific letters of the DNA code in human cells and to change the activity of targeted genes.

Importantly, the NovaIscB-based tools are compact enough to be easily packaged inside a single adeno-associated virus (AAV) — the vector most commonly used to safely deliver gene therapy to patients. Because they are bulkier, tools developed using Cas9 can require a more complicated delivery strategy.

Demonstrating NovaIscB’s potential for therapeutic use, Zhang’s team created a tool called OMEGAoff that adds chemical markers to DNA to dial down the activity of specific genes. They programmed OMEGAoff to repress a gene involved in cholesterol regulation, then used AAV to deliver the system to the livers of mice, leading to lasting reductions in cholesterol levels in the animals’ blood.

The team expects that NovaIscB can be used to target genome editing tools to most human genes, and look forward to seeing how other labs deploy the new technology. They also hope others will adopt their evolution-guided approach to rational protein engineering. “Nature has such diversity, and its systems have different advantages and disadvantages,” Zhu says. “By learning about that natural diversity, we can make the systems we are trying to engineer better and better.”

This study was funded, in part, by the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics at MIT, Broad Institute Programmable Therapeutics Gift Donors, Pershing Square Foundation, William Ackman, Neri Oxman, the Phillips family, and J. and P. Poitras.

Sarah Alnegheimish’s research interests reside at the intersection of machine learning and systems engineering. Her objective: to make machine learning systems more accessible, transparent, and trustworthy.

Alnegheimish is a PhD student in Principal Research Scientist Kalyan Veeramachaneni’s Data-to-AI group in MIT’s Laboratory for Information and Decision Systems (LIDS). Here, she commits most of her energy to developing Orion, an open-source, user-friendly machine learning framework and time series library that is capable of detecting anomalies without supervision in large-scale industrial and operational settings.

Early influence 

The daughter of a university professor and a teacher educator, she learned from an early age that knowledge was meant to be shared freely. “I think growing up in a home where education was highly valued is part of why I want to make machine learning tools accessible.” Alnegheimish’s own personal experience with open-source resources only increased her motivation. “I learned to view accessibility as the key to adoption. To strive for impact, new technology needs to be accessed and assessed by those who need it. That’s the whole purpose of doing open-source development.”

Alnegheimish earned her bachelor’s degree at King Saud University (KSU). “I was in the first cohort of computer science majors. Before this program was created, the only other available major in computing was IT [information technology].” Being a part of the first cohort was exciting, but it brought its own unique challenges. “All of the faculty were teaching new material. Succeeding required an independent learning experience. That’s when I first time came across MIT OpenCourseWare: as a resource to teach myself.”

Shortly after graduating, Alnegheimish became a researcher at the King Abdulaziz City for Science and Technology (KACST), Saudi Arabia’s national lab. Through the Center for Complex Engineering Systems (CCES) at KACST and MIT, she began conducting research with Veeramachaneni. When she applied to MIT for graduate school, his research group was her top choice.

Creating Orion

Alnegheimish’s master thesis focused on time series anomaly detection — the identification of unexpected behaviors or patterns in data, which can provide users crucial information. For example, unusual patterns in network traffic data can be a sign of cybersecurity threats, abnormal sensor readings in heavy machinery can predict potential future failures, and monitoring patient vital signs can help reduce health complications. It was through her master’s research that Alnegheimish first began designing Orion.

Orion uses statistical and machine learning-based models that are continuously logged and maintained. Users do not need to be machine learning experts to utilize the code. They can analyze signals, compare anomaly detection methods, and investigate anomalies in an end-to-end program. The framework, code, and datasets are all open-sourced.

“With open source, accessibility and transparency are directly achieved. You have unrestricted access to the code, where you can investigate how the model works through understanding the code. We have increased transparency with Orion: We label every step in the model and present it to the user.” Alnegheimish says that this transparency helps enable users to begin trusting the model before they ultimately see for themselves how reliable it is.

“We’re trying to take all these machine learning algorithms and put them in one place so anyone can use our models off-the-shelf,” she says. “It’s not just for the sponsors that we work with at MIT. It’s being used by a lot of public users. They come to the library, install it, and run it on their data. It’s proving itself to be a great source for people to find some of the latest methods for anomaly detection.”

Repurposing models for anomaly detection

In her PhD, Alnegheimish is further exploring innovative ways to do anomaly detection using Orion. “When I first started my research, all machine-learning models needed to be trained from scratch on your data. Now we’re in a time where we can use pre-trained models,” she says. Working with pre-trained models saves time and computational costs. The challenge, though, is that time series anomaly detection is a brand-new task for them. “In their original sense, these models have been trained to forecast, but not to find anomalies,” Alnegheimish says. “We’re pushing their boundaries through prompt-engineering, without any additional training.”

Because these models already capture the patterns of time-series data, Alnegheimish believes they already have everything they need to enable them to detect anomalies. So far, her current results support this theory. They don’t surpass the success rate of models that are independently trained on specific data, but she believes they will one day.

Accessible design

Alnegheimish talks at length about the efforts she’s gone through to make Orion more accessible. “Before I came to MIT, I used to think that the crucial part of research was to develop the machine learning model itself or improve on its current state. With time, I realized that the only way you can make your research accessible and adaptable for others is to develop systems that make them accessible. During my graduate studies, I’ve taken the approach of developing my models and systems in tandem.”

The key element to her system development was finding the right abstractions to work with her models. These abstractions provide universal representation for all models with simplified components. “Any model will have a sequence of steps to go from raw input to desired output.  We’ve standardized the input and output, which allows the middle to be flexible and fluid. So far, all the models we’ve run have been able to retrofit into our abstractions.” The abstractions she uses have been stable and reliable for the last six years.

The value of simultaneously building systems and models can be seen in Alnegheimish’s work as a mentor. She had the opportunity to work with two master’s students earning their engineering degrees. “All I showed them was the system itself and the documentation of how to use it. Both students were able to develop their own models with the abstractions we’re conforming to. It reaffirmed that we’re taking the right path.”

Alnegheimish also investigated whether a large language model (LLM) could be used as a mediator between users and a system. The LLM agent she has implemented is able to connect to Orion without users needing to know the small details of how Orion works. “Think of ChatGPT. You have no idea what the model is behind it, but it’s very accessible to everyone.” For her software, users only know two commands: Fit and Detect. Fit allows users to train their model, while Detect enables them to detect anomalies.

“The ultimate goal of what I’ve tried to do is make AI more accessible to everyone,” she says. So far, Orion has reached over 120,000 downloads, and over a thousand users have marked the repository as one of their favorites on Github. “Traditionally, you used to measure the impact of research through citations and paper publications. Now you get real-time adoption through open source.”

MIT course 2.797/2.798 (Molecular Cellular and Tissue Biomechanics) teaches students about the role that mechanics plays in biology, with a focus on biomechanics and mechanobiology: “Two words that sound similar, but are actually very different,” says Ritu Raman, the Eugene Bell Career Development Professor of Tissue Engineering in the MIT Department of Mechanical Engineering.

Biomechanics, Raman explains, conveys the mechanical properties of biological materials, where mechanobiology teaches students how cells feel and respond to forces in their environment. “When students take this class, they're getting a really unique fusion of not only fundamentals of mechanics, but also emerging research in biomechanics and mechanobiology,” says Raman.

Raman and Peter So, professor of mechanical engineering, co-teach the course, which So says offers a concrete application of some of the basic theory. “We talk about some of the applications and why the fundamental concept is important.”

The pair recently revamped the curriculum to incorporate hands-on lab-learning through the campus BioMakers space and the Safety, Health, Environmental Discovery Lab (SHED) bioprinting makerspace. This updated approach invites students to “build with biology” and see how cells respond to forces in their environment in real time, and it was a change that was seemingly welcomed from the start, with the first offering yielding the course’s largest-ever enrollment.

“Many concepts in biomechanics and mechanobiology can be hard to conceptualize because they happen at length scales that we can't typically visualize,” Raman explains. “In the past, we've done our best to convey these ideas via pictures, videos, and equations. The lab component adds another dimension to our teaching methods. We hope that students seeing firsthand how living cells sense and respond to their environment helps the concepts sink in deeper and last longer in their memories.”

Makerspaces, which are located throughout the campus, offer tools and workspace for MIT community members to invent, prototype, and bring ideas to life. The Institute has over 40 design/build/project spaces that include facilities for 3D printing, glassblowing, wood and metal working, and more. The BioMakers space welcomes students engaged in hands-on bioengineering projects. SHED similarly leverages cutting-edge technologies across disciplines, including a new space focused on 3D bio-printing.

Kamakshi Subramanian, a cross-registered Wellesley College student, says she encountered a polymer model in a prior thermodynamics class, but wondered how she’d apply it. Taking this course gave her a new frame of reference. “I was like, ‘Why are we doing this?’ … and then I came here and I was like, ‘OK, thinking about entropy in this way is actually useful.’”

Raman says there’s a special kind of energy and excitement associated with being in a lab versus staying in the classroom. “It reminds me of going on a field trip when I was in elementary school,” she says, adding that seeing that energy in students during the course’s first run inspired the instructors to expand lab offerings even further in the second offering.  

“[In addition to] one main lab on the biomechanics of muscle contraction, we have added a second lab where students visit the SHED makerspace to learn about 3D bio-printing,” she says. “We have also incorporated an optional hands-on component into the final project, [and] most students in the class are taking advantage of this extra lab time to try exciting curiosity-driven experiments at the intersection of biology and mechanics.”

Raman and So, who were joined in teaching the second iteration of the course this semester by professor of biological engineering Mark Bathe, say they hope to continue to build the amount of hands-on time incorporated into the class in the coming years.

Ayi Agboglo, a Harvard-MIT Health Sciences and Technology graduate student who is studying the physical properties of red blood cells relevant to sickle cell disease (SCD), says taking the course introduced him to studies where mathematical models extracted mechanical properties of red blood cell (RBC) membranes in the context of SCD.

“In SCD, deoxygenation causes rigid protein fibers to form within cells, altering their mechanical and physical properties,” he explains. “This field of work has largely informed my research which focuses on measuring the physical properties of RBCs (mass, volume, and density) in both oxygenated and deoxygenated states. These measurements aim to reveal patient-specific differences in fiber formation — the primary pathological event in SCD — potentially uncovering new therapeutic opportunities.”

Agboglo, who works in Professor Cullen Buie’s lab at MIT and John Higgins’ lab at MGH, says, “I left [the class] not only understanding more about molecular mechanics, but also understanding just fundamentals about thermodynamics and energy and things that I think will be useful as a scientist in general.”

In addition to lab and lecture time, 2.797/2.798 students also had the opportunity to work with the Museum of Science, Boston and generate open-source educational resources about the interplay between mechanics and biology. These resources are now available on the museum's website. 

School is almost out for summer! You know what that means? Plenty of time to catch up on the latest digital rights news! Don't worry, though—EFF has you covered with our EFFector newsletter.

This edition of EFFector explains why efforts to privatize public airwaves would harm American TV viewers; goes over how KOSA is still a very bad censorship bill, especially for young people; and covers how Signal, WhatsApp, and other encrypted chat apps back up your conversations.

You can read the full newsletter here, and even get future editions directly to your inbox when you subscribe! Additionally, we've got an audio edition of EFFector on the Internet Archive, or you can view it by clicking the button below:

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EFFECTOR 37.5 - The Insidious Effort to Privatize Public Airwaves

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Consuming a high-fat diet can lead to a variety of health problems — not only weight gain but also an increased risk of diabetes and other chronic diseases.

At the cellular level, hundreds of changes take place in response to a high-fat diet. MIT researchers have now mapped out some of those changes, with a focus on metabolic enzyme dysregulation that is associated with weight gain.

Their study, conducted in mice, revealed that hundreds of enzymes involved in sugar, lipid, and protein metabolism are affected by a high-fat diet, and that these disruptions lead to an increase in insulin resistance and an accumulation of damaging molecules called reactive oxygen species. These effects were more pronounced in males than females.

The researchers also showed that most of the damage could be reversed by giving the mice an antioxidant along with their high-fat diet.

“Under metabolic stress conditions, enzymes can be affected to produce a more harmful state than what was initially there,” says Tigist Tamir, a former MIT postdoc. “Then what we’ve shown with the antioxidant study is that you can bring them to a different state that is less dysfunctional.”

Tamir, who is now an assistant professor of biochemistry and biophysics at the University of North Carolina at Chapel Hill School of Medicine, is the lead author of the new study, which appears today in Molecular Cell. Forest White, the Ned C. and Janet C. Rice Professor of Biological Engineering and a member of the Koch Institute for Integrative Cancer Research at MIT, is the senior author of the paper.

Metabolic networks

In previous work, White’s lab has found that a high-fat diet stimulates cells to turn on many of the same signaling pathways that are linked to chronic stress. In the new study, the researchers wanted to explore the role of enzyme phosphorylation in those responses.

Phosphorylation, or the addition of a phosphate group, can turn enzyme activity on or off. This process, which is controlled by enzymes called kinases, gives cells a way to quickly respond to environmental conditions by fine-tuning the activity of existing enzymes within the cell.

Many enzymes involved in metabolism — the conversion of food into the building blocks of key molecules such as proteins, lipids, and nucleic acids — are known to undergo phosphorylation.

The researchers began by analyzing databases of human enzymes that can be phosphorylated, focusing on enzymes involved in metabolism. They found that many of the metabolic enzymes that undergo phosphorylation belong to a class called oxidoreductases, which transfer electrons from one molecule to another. Such enzymes are key to metabolic reactions such as glycolysis — the breakdown of glucose into a smaller molecule known as pyruvate.

Among the hundreds of enzymes the researchers identified are IDH1, which is involved in breaking down sugar to generate energy, and AKR1C1, which is required for metabolizing fatty acids. The researchers also found that many phosphorylated enzymes are important for the management of reactive oxygen species, which are necessary for many cell functions but can be harmful if too many of them accumulate in a cell.

Phosphorylation of these enzymes can lead them to become either more or less active, as they work together to respond to the intake of food. Most of the metabolic enzymes identified in this study are phosphorylated on sites found in regions of the enzyme that are important for binding to the molecules that they act upon or for forming dimers — pairs of proteins that join together to form a functional enzyme.

“Tigist’s work has really shown categorically the importance of phosphorylation in controlling the flux through metabolic networks. It’s fundamental knowledge that emerges from this systemic study that she’s done, and it’s something that is not classically captured in the biochemistry textbooks,” White says.

Out of balance

To explore these effects in an animal model, the researchers compared two groups of mice, one that received a high-fat diet and one that consumed a normal diet. They found that overall, phosphorylation of metabolic enzymes led to a dysfunctional state in which cells were in redox imbalance, meaning that their cells were producing more reactive oxygen species than they could neutralize. These mice also became overweight and developed insulin resistance.

“In the context of continued high fat diet, what we see is a gradual drift away from redox homeostasis towards a more disease-like setting,” White says.

These effects were much more pronounced in male mice than female mice. Female mice were better able to compensate for the high fat diet by activating pathways involved in processing fat and metabolizing it for other uses, the researchers found.

“One of the things we learned is that the overall systemic effect of these phosphorylation events led to, especially in males, an increased imbalance in redox homeostasis. They were expressing a lot more stress and a lot more of the metabolic dysfunction phenotype compared to females,” Tamir says.

The researchers also found that if they gave mice who were on a high-fat diet an antioxidant called BHA, many of these effects were reversed. These mice showed a significant decrease in weight gain and did not become prediabetic, unlike the other mice fed a high-fat diet.

It appears that the antioxidant treatment leads cells back into a more balanced state, with fewer reactive oxygen species, the researchers say. Additionally, metabolic enzymes showed a systemic rewiring and changed state of phosphorylation in those mice.

“They’re experiencing a lot of metabolic dysfunction, but if you co-administer something that counters that, then they have enough reserve to maintain some sort of normalcy,” Tamir says. “The study suggests that there is something biochemically happening in cells to bring them to a different state — not a normal state, just a different state in which now, at the tissue and organism levels, the mice are healthier.”

In her new lab at the University of North Carolina, Tamir now plans to further explore whether antioxidant treatment could be an effective way to prevent or treat obesity-associated metabolic dysfunction, and what the optimal timing of such a treatment would be.

The research was funded in part by the Burroughs Wellcome Fund, the National Cancer Institute, the National Institutes of Health, the Ludwig Center at MIT, and the MIT Center for Precision Cancer Medicine.

A $20 million gift from the Leinweber Foundation, in addition to a $5 million commitment from the MIT School of Science, will support theoretical physics research and education at MIT.

Leinweber Foundation gifts to five institutions, totaling $90 million, will establish the newly renamed MIT Center for Theoretical Physics – A Leinweber Institute within the Department of Physics, affiliated with the Laboratory for Nuclear Science at the School of Science, as well as Leinweber Institutes for Theoretical Physics at three other top research universities: the University of Michigan, the University of California at Berkeley, and the University of Chicago, as well as a Leinweber Forum for Theoretical and Quantum Physics at the Institute for Advanced Study.

“MIT has one of the strongest and broadest theory groups in the world,” says Professor Washington Taylor, the director of the newly funded center and a leading researcher in string theory and its connection to observable particle physics and cosmology.

“This landmark endowment from the Leinweber Foundation will enable us to support the best graduate students and postdoctoral researchers to develop their own independent research programs and to connect with other researchers in the Leinweber Institute network. By pledging to support this network and fundamental curiosity-driven science, Larry Leinweber and his family foundation have made a huge contribution to maintaining a thriving scientific enterprise in the United States in perpetuity.”

The Leinweber Foundation’s investment across five institutions — constituting the largest philanthropic commitment ever for theoretical physics research, according to the Science Philanthropy Alliance, a nonprofit organization that supports philanthropic support for science — will strengthen existing programs at each institution and foster collaboration across the universities. Recipient institutions will work both independently and collaboratively to explore foundational questions in theoretical physics. Each institute will continue to shape its own research focus and programs, while also committing to big-picture cross-institutional convenings around topics of shared interest. Moreover, each institute will have significantly more funding for graduate students and postdocs, including fellowship support for three to eight fully endowed Leinweber Physics Fellows at each institute.

“This gift is a commitment to America’s scientific future,” says Larry Leinweber, founder and president of the Leinweber Foundation. “Theoretical physics may seem abstract to many, but it is the tip of the spear for innovation. It fuels our understanding of how the world works and opens the door to new technologies that can shape society for generations. As someone who has had a lifelong fascination with theoretical physics, I hope this investment not only strengthens U.S. leadership in basic science, but also inspires curiosity, creativity, and groundbreaking discoveries for generations to come.”

The gift to MIT will create a postdoc program that, once fully funded, will initially provide support for up to six postdocs, with two selected per year for a three-year program. In addition, the gift will provide student financial support, including fellowship support, for up to six graduate students per year studying theoretical physics. The goal is to attract the top talent to the MIT Center for Theoretical Physics – A Leinweber Institute and support the ongoing research programs in a more robust way.

A portion of the funding will also provide support for visitors, seminars, and other scholarly activities of current postdocs, faculty, and students in theoretical physics, as well as helping with administrative support.

“Graduate students are the heart of our country’s scientific research programs. Support for their education to become the future leaders of the field is essential for the advancement of the discipline,” says Nergis Mavalvala, dean of the MIT School of Science and the Curtis (1963) and Kathleen Marble Professor of Astrophysics.

The Leinweber Foundation gift is the second significant gift for the center. “We are always grateful to Virgil Elings, whose generous gift helped make possible the space that houses the center,” says Deepto Chakrabarty, head of the Department of Physics. Elings PhD ’66, co-founder of Digital Instruments, which designed and sold scanning probe microscopes, made his gift more than 20 years ago to support a space for theoretical physicists to collaborate.

“Gifts like those from Larry Leinweber and Virgil Elings are critical, especially now in this time of uncertain funding from the federal government for support of fundamental scientific research carried out by our nation’s leading postdocs, research scientists, faculty and students,” adds Mavalvala.

Professor Tracy Slatyer, whose work is motivated by questions of fundamental particle physics — particularly the nature and interactions of dark matter — will be the subsequent director of the MIT Center for Theoretical Physics – A Leinweber Institute beginning this fall. Slatyer will join Mavalvala, Taylor, Chakrabarty, and the entirety of the theoretical physics community for a dedication ceremony planned for the near future.

The Leinweber Foundation was founded in 2015 by software entrepreneur Larry Leinweber, and has worked with the Science Philanthropy Alliance since 2021 to shape its philanthropic strategy. “It’s been a true pleasure to work with Larry and the Leinweber family over the past four years and to see their vision take shape,” says France Córdova, president of the Science Philanthropy Alliance. “Throughout his life, Larry has exemplified curiosity, intellectual openness, and a deep commitment to learning. This gift reflects those values, ensuring that generations of scientists will have the freedom to explore, to question, and to pursue ideas that could change how we understand the universe.”

Russia is proposing a rule that all foreigners in Moscow install a tracking app on their phones.

Using a mobile application that all foreigners will have to install on their smartphones, the Russian state will receive the following information:

• Residence location
• Fingerprint
• Face photograph
• Real-time geo-location monitoring

This isn’t the first time we’ve seen this. Qatar did it in 2022 around the World Cup:

“After accepting the terms of these apps, moderators will have complete control of users’ devices,” he continued. “All personal content, the ability to edit it, share it, extract it as well as data from other apps on your device is in their hands. Moderators will even have the power to unlock users’ devices remotely.” ...

The Republican-controlled Legislature is diluting a climate lawsuit that they say was won by a "bunch of little Greta Thunbergs."

The Biden administration sharply increased the maximum size of disaster loans for the first time in three decades. Los Angeles residents who survived January’s inferno got much of the money.

Opponents of offshore wind were aghast over the sighting of a 660-foot-long crane ship in Narragansett Bay, Rhode Island.

The king's rare address before the Canadian Parliament came after President Donald Trump threatened to annex the country.

The demand goes one step beyond a push to include regulated carbon offsets, further complicating the EU’s attempt to set a 2040 goal.

The one-day conference, dubbed the Everest Summiteers Summit, involved discussions on how to protect climbers and the environment.

The car company also faces other factors including an aging model lineup and intensifying Chinese competition.

One goal of the Bharat Forecast System is to better predict rainfall, which has long been a challenge in tropical climates.

This semester, MIT D-Lab students built prototype solutions to help farmers in Afghanistan, people living in informal settlements in Argentina, and rural poultry farmers in Cameroon. The projects span continents and collectively stand to improve thousands of lives — and they all trace back to two longstanding MIT D-Lab classes.

For nearly two decades, 2.651 / EC.711 (Introduction to Energy in Global Development) and 2.652 / EC.712 (Applications of Energy in Global Development) have paired students with international organizations and communities to learn D-Lab’s participatory approach to design and study energy technologies in low-resource environments. Hundreds of students from across MIT have taken the courses, which feature visits from partners and trips to the communities after the semester. They often discover a passion for helping people in low-resource settings that lasts a lifetime.

“Through the trips, students often gain an appreciation for what they have at home, and they can’t forget about what they see,” says D-Lab instructor Josh Maldonado ’23, who took both courses as a student. “For me, it changed my entire career. Students maintain relationships with the people they work with. They stay on the group chats with community members and meet up with them when they travel. They come back and want to mentor for the class. You can just see it has a lasting effect.”

The introductory course takes place each spring and is followed by summer trips for students. The applications class, which is more focused on specific projects, is held in the fall and followed by student travel over winter break.

“MIT has always advocated for going out and impacting the world,” Maldonado says. “The fact that we can use what we learn here in such a meaningful way while still a student is awesome. It gets back to MIT’s motto, ‘mens et manus’ (‘mind and hand’).”

Curriculum for impact

Introduction to Energy in Global Development has been taught since around 2008, with past projects focusing on mitigating the effects of aquatic weeds for fisherman in Ghana, making charcoal for cookstoves in Uganda, and creating brick evaporative coolers to extend the shelf life of fruits and vegetables in Mali.

The class follows MIT D-Lab’s participatory design philosophy in which students design solutions in close collaboration with local communities. Along the way, students learn about different energy technologies and how they might be implemented cheaply in rural communities that lack basic infrastructure.

“In product design, the idea is to get out and meet your customer where they are,” Maldonado explains. “The problem is our partners are often in remote, low-resource regions of the world. We put a big emphasis on designing with the local communities and increasing their creative capacity building to show them they can build solutions themselves.”

Students from across MIT, including graduates and undergraduates, along with students from Harvard University and Wellesley College, can enroll in both courses. MIT senior Kanokwan Tungkitkancharoen took the introductory class this spring.

“There are students from chemistry, computer science, civil engineering, policy, and more,” says Tungkitkancharoen. “I think that convergence models how things get done in real life. The class also taught me how to communicate the same information in different ways to cater to different people. It helped me distill my approach to what is this person trying to learn and how can I convey that information.”

Tungkitkancharoen’s team worked with a nonprofit called Weatherizers Without Borders to implement weatherization strategies that enhance housing conditions and environmental resilience for people in the southern Argentinian community of Bariloche.

The team built model homes and used heat sensing cameras to show the impact of weatherization strategies to locals and policymakers in the region.

“Our partners live in self-built homes, but the region is notorious for being very cold in the winter and very hot in the summer,” Tungkitkancharoen says. “We’re helping our partners retrofit homes so they can withstand the weather better. Before the semester, I was interested in working directly with people impacted by these technologies and the current climate situation. D-Lab helped me work with people on the ground, and I’ve been super grateful to our community partners.”

The project to design micro-irrigation systems to support agricultural productivity and water conservation in Afghanistan is in partnership with the Ecology and Conservation Organization of Afghanistan and a team from a local university in Afghanistan.

“I love the process of coming into class with a practical question you need to solve and working closely with community partners,” says MIT master’s student Khadija Ghanizada, who has served as a teacher’s assistant for both the introductory and applications courses. “All of these projects will have a huge impact, but being from Afghanistan, I know this will make a difference because it’s a land-locked country, it’s dealing with droughts, and 80 percent of our economy depends on agriculture. We also make sure students are thinking about scalability of their solutions, whether scaling worldwide or just nationally. Every project has its own impact story.”

Meeting community partners

Now that the spring semester is over, many students from the introductory class will travel to the regions they studied with instructors and local guides over the summer.

“The traveling and implementation are things students always look forward to,” Maldonado says. “Students do a lot of prep work, thinking about the tools they need, the local resources they need, and working with partners to acquire those resources.”

Following travel, students write a report on how the trip went, which helps D-Lab refine the course for next semester.

“Oftentimes instructors are also doing research in these regions while they teach the class,” Maldonado says. “To be taught by people who were just in the field two weeks before the class started, and to see pictures of what they’re doing, is really powerful.”

Students who have taken the class have gone on to careers in international development, nonprofits, and to start companies that grow the impact of their class projects. But the most immediate impact can be seen in the communities that students work with.

“These solutions should be able to be built locally, sourced locally, and potentially also lead to the creation of localized markets based around the technology,” Maldonado says. “Almost everything the D-Lab does is open-sourced, so when we go to these communities, we don’t just teach people how to use these solutions, we teach them how to make them. Technology, if implemented correctly by mindful engineers and scientists, can be highly adopted and can grow a community of makers and fabricators and local businesses.”

Nature Climate Change, Published online: 28 May 2025; doi:10.1038/s41558-025-02344-8

Emerging agroforestry initiatives focus on planting trees rather than managing existing forestland. The result is a missed opportunity to support forest ecosystems, rural livelihoods and climate mitigation.

Long before she stepped into a lab, Ananda Santos Figueiredo was stargazing in Brazil, captivated by the cosmos and feeding her curiosity of science through pop culture, books, and the internet. She was drawn to astrophysics for its blend of visual wonder and mathematics.

Even as a child, Santos sensed her aspirations reaching beyond the boundaries of her hometown. “I’ve always been drawn to STEM,” she says. “I had this persistent feeling that I was meant to go somewhere else to learn more, explore, and do more.”

Her parents saw their daughter’s ambitions as an opportunity to create a better future. The summer before her sophomore year of high school, her family moved from Brazil to Florida.  She recalls that moment as “a big leap of faith in something bigger and we had no idea how it would turn out.” She was certain of one thing: She wanted an education that was both technically rigorous and deeply expansive, one that would allow her to pursue all her passions.

At MIT, she found exactly what she was seeking in a community and curriculum that matched her curiosity and ambition. “I’ve always associated MIT with something new and exciting that was grasping towards the very best we can achieve as humans,” Santos says, emphasizing the use of technology and science to significantly impact society. “It’s a place where people aren’t afraid to dream big and work hard to make it a reality.”

As a first-generation college student, she carried the weight of financial stress and the uncertainty that comes with being the first in her family to navigate college in the U.S. But she found a sense of belonging in the MIT community. “Being a first-generation student helped me grow,” she says. “It inspired me to seek out opportunities and help support others too.”

She channeled that energy into student government roles for the undergraduate residence halls. Through Dormitory Council (DormCon) and her dormitory, Simmons Hall, her voice could help shape life on campus. She began serving as reservations chair for her dormitory but ended up becoming president of the dormitory before being elected dining chair and vice president for DormCon. She’s worked to improve dining hall operations and has planned major community events like Simmons Hall’s 20th anniversary and DormCon’s inaugural Field Day.

Now, a senior about to earn her bachelor’s degree, Santos says MIT’s motto, “mens et manus” — “mind and hand” — has deeply resonated with her from the start. “Learning here goes far beyond the classroom,” she says. “I’ve been surrounded by people who are passionate and purposeful. That energy is infectious. It’s changed how I see myself and what I believe is possible.”

Charting her own course

Initially a physics major, Santos’ academic path took a turn after a transformative internship with the World Bank’s data science lab between her sophomore and junior years. There, she used her coding skills to study the impacts of heat waves in the Philippines. The experience opened her eyes to the role technology and data can play in improving lives and broadened her view of what a STEM career could look like.

“I realized I didn’t want to just study the universe — I wanted to change it,” she says. “I wanted to join systems thinking with my interest in the humanities, to build a better world for people and communities."

When MIT launched a new major in climate system science and engineering (Course 1-12) in 2023, Santos was the first student to declare it. The interdisciplinary structure of the program, blending climate science, engineering, energy systems, and policy, gave her a framework to connect her technical skills to real-world sustainability challenges.

She tailored her coursework to align with her passions and career goals, applying her physics background (now her minor) to understand problems in climate, energy, and sustainable systems. “One of the most powerful things about the major is the breadth,” she says. “Even classes that aren’t my primary focus have expanded how I think.”

Hands-on fieldwork has been a cornerstone of her learning. During MIT’s Independent Activities Period (IAP), she studied climate impacts in Hawai’i in the IAP Course 1.091 (Traveling Research Environmental Experiences, or TREX). This year, she studied the design of sustainable polymer systems in Course 1.096/10.496 (Design of Sustainable Polymer Systems) under MISTI’s Global Classroom program. The IAP class brought her to the middle of the Amazon Rainforest to see what the future of plastic production could look like with products from the Amazon. “That experience was incredibly eye opening,” she explains. “It helped me build a bridge between my own background and the kind of problems that I want to solve in the future.”

Santos also found enjoyment beyond labs and lectures. A member of the MIT Shakespeare Ensemble since her first year, she took to the stage in her final spring production of “Henry V,” performing as both the Chorus and Kate. “The ensemble’s collaborative spirit and the way it brings centuries-old texts to life has been transformative,” she adds.

Her passion for the arts also intersected with her interest in the MIT Lecture Series Committee. She helped host a special screening of the film “Sing Sing,” in collaboration with MIT’s Educational Justice Institute (TEJI). That connection led her to enroll in a TEJI course, illustrating the surprising and meaningful ways that different parts of MIT’s ecosystem overlap. “It’s one of the beautiful things about MIT,” she says. “You stumble into experiences that deeply change you.”

Throughout her time at MIT, the community of passionate, sustainability-focused individuals has been a major source of inspiration. She’s been actively involved with the MIT Office of Sustainability’s decarbonization initiatives and participated in the Climate and Sustainability Scholars Program.

Santos acknowledges that working in sustainability can sometimes feel overwhelming. “Tackling the challenges of sustainability can be discouraging,” she says. “The urgency to create meaningful change in a short period of time can be intimidating. But being surrounded by people who are actively working on it is so much better than not working on it at all."

Looking ahead, she plans to pursue graduate studies in technology and policy, with aspirations to shape sustainable development, whether through academia, international organizations, or diplomacy.

“The most fulfilling moments I’ve had at MIT are when I’m working on hard problems while also reflecting on who I want to be, what kind of future I want to help create, and how we can be better and kinder to each other,” she says. “That’s what excites me — solving real problems that matter.”

Batteries are nearing their limits in terms of how much power they can store for a given weight. That’s a serious obstacle for energy innovation and the search for new ways to power airplanes, trains, and ships. Now, researchers at MIT and elsewhere have come up with a solution that could help electrify these transportation systems.

Instead of a battery, the new concept is a kind of fuel cell — which is similar to a battery but can be quickly refueled rather than recharged. In this case, the fuel is liquid sodium metal, an inexpensive and widely available commodity. The other side of the cell is just ordinary air, which serves as a source of oxygen atoms. In between, a layer of solid ceramic material serves as the electrolyte, allowing sodium ions to pass freely through, and a porous air-facing electrode helps the sodium to chemically react with oxygen and produce electricity.

In a series of experiments with a prototype device, the researchers demonstrated that this cell could carry more than three times as much energy per unit of weight as the lithium-ion batteries used in virtually all electric vehicles today. Their findings are being published today in the journal Joule, in a paper by MIT doctoral students Karen Sugano, Sunil Mair, and Saahir Ganti-Agrawal; professor of materials science and engineering Yet-Ming Chiang; and five others.

“We expect people to think that this is a totally crazy idea,” says Chiang, who is the Kyocera Professor of Ceramics. “If they didn’t, I’d be a bit disappointed because if people don’t think something is totally crazy at first, it probably isn’t going to be that revolutionary.”

And this technology does appear to have the potential to be quite revolutionary, he suggests. In particular, for aviation, where weight is especially crucial, such an improvement in energy density could be the breakthrough that finally makes electrically powered flight practical at significant scale.

“The threshold that you really need for realistic electric aviation is about 1,000 watt-hours per kilogram,” Chiang says. Today’s electric vehicle lithium-ion batteries top out at about 300 watt-hours per kilogram — nowhere near what’s needed. Even at 1,000 watt-hours per kilogram, he says, that wouldn’t be enough to enable transcontinental or trans-Atlantic flights.

That’s still beyond reach for any known battery chemistry, but Chiang says that getting to 1,000 watts per kilogram would be an enabling technology for regional electric aviation, which accounts for about 80 percent of domestic flights and 30 percent of the emissions from aviation.

The technology could be an enabler for other sectors as well, including marine and rail transportation. “They all require very high energy density, and they all require low cost,” he says. “And that’s what attracted us to sodium metal.”

A great deal of research has gone into developing lithium-air or sodium-air batteries over the last three decades, but it has been hard to make them fully rechargeable. “People have been aware of the energy density you could get with metal-air batteries for a very long time, and it’s been hugely attractive, but it’s just never been realized in practice,” Chiang says.

By using the same basic electrochemical concept, only making it a fuel cell instead of a battery, the researchers were able to get the advantages of the high energy density in a practical form. Unlike a battery, whose materials are assembled once and sealed in a container, with a fuel cell the energy-carrying materials go in and out.

The team produced two different versions of a lab-scale prototype of the system. In one, called an H cell, two vertical glass tubes are connected by a tube across the middle, which contains a solid ceramic electrolyte material and a porous air electrode. Liquid sodium metal fills the tube on one side, and air flows through the other, providing the oxygen for the electrochemical reaction at the center, which ends up gradually consuming the sodium fuel. The other prototype uses a horizontal design, with a tray of the electrolyte material holding the liquid sodium fuel. The porous air electrode, which facilitates the reaction, is affixed to the bottom of the tray. 

Tests using an air stream with a carefully controlled humidity level produced a level of more than 1,500 watt-hours per kilogram at the level of an individual “stack,” which would translate to over 1,000 watt-hours at the full system level, Chiang says.

The researchers envision that to use this system in an aircraft, fuel packs containing stacks of cells, like racks of food trays in a cafeteria, would be inserted into the fuel cells; the sodium metal inside these packs gets chemically transformed as it provides the power. A stream of its chemical byproduct is given off, and in the case of aircraft this would be emitted out the back, not unlike the exhaust from a jet engine.

But there’s a very big difference: There would be no carbon dioxide emissions. Instead the emissions, consisting of sodium oxide, would actually soak up carbon dioxide from the atmosphere. This compound would quickly combine with moisture in the air to make sodium hydroxide — a material commonly used as a drain cleaner — which readily combines with carbon dioxide to form a solid material, sodium carbonate, which in turn forms sodium bicarbonate, otherwise known as baking soda.

“There’s this natural cascade of reactions that happens when you start with sodium metal,” Chiang says. “It’s all spontaneous. We don’t have to do anything to make it happen, we just have to fly the airplane.”

As an added benefit, if the final product, the sodium bicarbonate, ends up in the ocean, it could help to de-acidify the water, countering another of the damaging effects of greenhouse gases.

Using sodium hydroxide to capture carbon dioxide has been proposed as a way of mitigating carbon emissions, but on its own, it’s not an economic solution because the compound is too expensive. “But here, it’s a byproduct,” Chiang explains, so it’s essentially free, producing environmental benefits at no cost.

Importantly, the new fuel cell is inherently safer than many other batteries, he says. Sodium metal is extremely reactive and must be well-protected. As with lithium batteries, sodium can spontaneously ignite if exposed to moisture. “Whenever you have a very high energy density battery, safety is always a concern, because if there’s a rupture of the membrane that separates the two reactants, you can have a runaway reaction,” Chiang says. But in this fuel cell, one side is just air, “which is dilute and limited. So you don’t have two concentrated reactants right next to each other. If you’re pushing for really, really high energy density, you’d rather have a fuel cell than a battery for safety reasons.”

While the device so far exists only as a small, single-cell prototype, Chiang says the system should be quite straightforward to scale up to practical sizes for commercialization. Members of the research team have already formed a company, Propel Aero, to develop the technology. The company is currently housed in MIT’s startup incubator, The Engine.

Producing enough sodium metal to enable widespread, full-scale global implementation of this technology should be practical, since the material has been produced at large scale before. When leaded gasoline was the norm, before it was phased out, sodium metal was used to make the tetraethyl lead used as an additive, and it was being produced in the U.S. at a capacity of 200,000 tons a year. “It reminds us that sodium metal was once produced at large scale and safely handled and distributed around the U.S.,” Chiang says.

What’s more, sodium primarily originates from sodium chloride, or salt, so it is abundant, widely distributed around the world, and easily extracted, unlike lithium and other materials used in today’s EV batteries.

The system they envisage would use a refillable cartridge, which would be filled with liquid sodium metal and sealed. When it’s depleted, it would be returned to a refilling station and loaded with fresh sodium. Sodium melts at 98 degrees Celsius, just below the boiling point of water, so it is easy to heat to the melting point to refuel the cartridges.

Initially, the plan is to produce a brick-sized fuel cell that can deliver about 1,000 watt-hours of energy, enough to power a large drone, in order to prove the concept in a practical form that could be used for agriculture, for example. The team hopes to have such a demonstration ready within the next year.

Sugano, who conducted much of the experimental work as part of her doctoral thesis and will now work at the startup, says that a key insight was the importance of moisture in the process. As she tested the device with pure oxygen, and then with air, she found that the amount of humidity in the air was crucial to making the electrochemical reaction efficient. The humid air resulted in the sodium producing its discharge products in liquid rather than solid form, making it much easier for these to be removed by the flow of air through the system. “The key was that we can form this liquid discharge product and remove it easily, as opposed to the solid discharge that would form in dry conditions,” she says.

Ganti-Agrawal notes that the team drew from a variety of different engineering subfields. For example, there has been much research on high-temperature sodium, but none with a system with controlled humidity. “We’re pulling from fuel cell research in terms of designing our electrode, we’re pulling from older high-temperature battery research as well as some nascent sodium-air battery research, and kind of mushing it together,” which led to the “the big bump in performance” the team has achieved, he says.

The research team also included Alden Friesen, an MIT summer intern who attends Desert Mountain High School in Scottsdale, Arizona; Kailash Raman and William Woodford of Form Energy in Somerville, Massachusetts; Shashank Sripad of And Battery Aero in California, and Venkatasubramanian Viswanathan of the University of Michigan. The work was supported by ARPA-E, Breakthrough Energy Ventures, and the National Science Foundation, and used facilities at MIT.nano.

The human brain contains about 86 billion neurons. These cells fire electrical signals that help the brain store memories and send information and commands throughout the brain and the nervous system.

The brain also contains billions of astrocytes — star-shaped cells with many long extensions that allow them to interact with millions of neurons. Although they have long been thought to be mainly supportive cells, recent studies have suggested that astrocytes may play a role in memory storage and other cognitive functions.

MIT researchers have now put forth a new hypothesis for how astrocytes might contribute to memory storage. The architecture suggested by their model would help to explain the brain’s massive storage capacity, which is much greater than would be expected using neurons alone.

“Originally, astrocytes were believed to just clean up around neurons, but there’s no particular reason that evolution did not realize that, because each astrocyte can contact hundreds of thousands of synapses, they could also be used for computation,” says Jean-Jacques Slotine, an MIT professor of mechanical engineering and of brain and cognitive sciences, and an author of the new study.

Dmitry Krotov, a research staff member at the MIT-IBM Watson AI Lab and IBM Research, is the senior author of the open-access paper, which appeared May 23 in the Proceedings of the National Academy of Sciences. Leo Kozachkov PhD ’22 is the paper’s lead author.

Memory capacity

Astrocytes have a variety of support functions in the brain: They clean up debris, provide nutrients to neurons, and help to ensure an adequate blood supply.

Astrocytes also send out many thin tentacles, known as processes, which can each wrap around a single synapse — the junctions where two neurons interact with each other — to create a tripartite (three-part) synapse.

Within the past couple of years, neuroscientists have shown that if the connections between astrocytes and neurons in the hippocampus are disrupted, memory storage and retrieval are impaired.

Unlike neurons, astrocytes can’t fire action potentials, the electrical impulses that carry information throughout the brain. However, they can use calcium signaling to communicate with other astrocytes. Over the past few decades, as the resolution of calcium imaging has improved, researchers have found that calcium signaling also allows astrocytes to coordinate their activity with neurons in the synapses that they associate with.

These studies suggest that astrocytes can detect neural activity, which leads them to alter their own calcium levels. Those changes may trigger astrocytes to release gliotransmitters — signaling molecules similar to neurotransmitters — into the synapse.

“There’s a closed circle between neuron signaling and astrocyte-to-neuron signaling,” Kozachkov says. “The thing that is unknown is precisely what kind of computations the astrocytes can do with the information that they’re sensing from neurons.”

The MIT team set out to model what those connections might be doing and how they might contribute to memory storage. Their model is based on Hopfield networks — a type of neural network that can store and recall patterns.

Hopfield networks, originally developed by John Hopfield and Shun-Ichi Amari in the 1970s and 1980s, are often used to model the brain, but it has been shown that these networks can’t store enough information to account for the vast memory capacity of the human brain. A newer, modified version of a Hopfield network, known as dense associative memory, can store much more information through a higher order of couplings between more than two neurons.

However, it is unclear how the brain could implement these many-neuron couplings at a hypothetical synapse, since conventional synapses only connect two neurons: a presynaptic cell and a postsynaptic cell. This is where astrocytes come into play.

“If you have a network of neurons, which couple in pairs, there’s only a very small amount of information that you can encode in those networks,” Krotov says. “In order to build dense associative memories, you need to couple more than two neurons. Because a single astrocyte can connect to many neurons, and many synapses, it is tempting to hypothesize that there might exist an information transfer between synapses mediated by this biological cell. That was the biggest inspiration for us to look into astrocytes and led us to start thinking about how to build dense associative memories in biology.”

The neuron-astrocyte associative memory model that the researchers developed in their new paper can store significantly more information than a traditional Hopfield network — more than enough to account for the brain’s memory capacity.

Intricate connections

The extensive biological connections between neurons and astrocytes offer support for the idea that this type of model might explain how the brain’s memory storage systems work, the researchers say. They hypothesize that within astrocytes, memories are encoded by gradual changes in the patterns of calcium flow. This information is conveyed to neurons by gliotransmitters released at synapses that astrocyte processes connect to.

“By careful coordination of these two things — the spatial temporal pattern of calcium in the cell and then the signaling back to the neurons — you can get exactly the dynamics you need for this massively increased memory capacity,” Kozachkov says.

One of the key features of the new model is that it treats astrocytes as collections of processes, rather than a single entity. Each of those processes can be considered one computational unit. Because of the high information storage capabilities of dense associative memories, the ratio of the amount of information stored to the number of computational units is very high and grows with the size of the network. This makes the system not only high capacity, but also energy efficient.

“By conceptualizing tripartite synaptic domains — where astrocytes interact dynamically with pre- and postsynaptic neurons — as the brain’s fundamental computational units, the authors argue that each unit can store as many memory patterns as there are neurons in the network. This leads to the striking implication that, in principle, a neuron-astrocyte network could store an arbitrarily large number of patterns, limited only by its size,” says Maurizio De Pitta, an assistant professor of physiology at the Krembil Research Institute at the University of Toronto, who was not involved in the study.

To test whether this model might accurately represent how the brain stores memory, researchers could try to develop ways to precisely manipulate the connections between astrocytes’ processes, then observe how those manipulations affect memory function.

“We hope that one of the consequences of this work could be that experimentalists would consider this idea seriously and perform some experiments testing this hypothesis,” Krotov says.

In addition to offering insight into how the brain may store memory, this model could also provide guidance for researchers working on artificial intelligence. By varying the connectivity of the process-to-process network, researchers could generate a huge range of models that could be explored for different purposes, for instance, creating a continuum between dense associative memories and attention mechanisms in large language models.

“While neuroscience initially inspired key ideas in AI, the last 50 years of neuroscience research have had little influence on the field, and many modern AI algorithms have drifted away from neural analogies,” Slotine says. “In this sense, this work may be one of the first contributions to AI informed by recent neuroscience research.”