Teen builds an award-winning virtual reality prototype thanks to free MIT courses

When Freesia Gaul discovered MIT Open Learning’s OpenCourseWare at just 14 years old, it opened up a world of learning far beyond what her classrooms could offer. Her parents had started a skiing company, and the seasonal work meant that Gaul had to change schools every six months. Growing up in small towns in Australia and Canada, she relied on the internet to fuel her curiosity.

“I went to 13 different schools, which was hard because you're in a different educational system every single time,” says Gaul. “That’s one of the reasons I gravitated toward online learning and teaching myself. Knowledge is something that exists beyond a curriculum.”

The small towns she lived in often didn’t have a lot of resources, she says, so a computer served as a main tool for learning. She enjoyed engaging with Wikipedia, ultimately researching topics and writing and editing content for pages. In 2018, she discovered MIT OpenCourseWare, part of MIT Open Learning, and took her first course. OpenCouseWare offers free, online, open educational resources from more than 2,500 MIT undergraduate and graduate courses. 

“I really got started with the OpenCourseWare introductory electrical engineering classes, because I couldn’t find anything else quite like it online,” says Gaul, who was initially drawn to courses on circuits and electronics, such as 6.002 (Circuits and Electronics) and 6.01SC (Introduction to Electrical Engineering and Computer Science). “It really helped me in terms of understanding how electrical engineering worked in a practical sense, and I just started modding things.”

In true MIT “mens et manus” (“mind and hand”) fashion, Gaul spent much of her childhood building and inventing, especially when she was able to access a 3D printer. She says that a highlight was when she built a life-sized, working version of a Mario Kart, constructed out of materials she had printed.

Gaul calls herself a “serial learner,” and has taken many OpenCourseWare courses. In addition to classes on circuits and electronics, she also took courses in linear algebra, calculus, and quantum physics — in which she took a particular interest. 

When she was 15, she participated in Qubit by Qubit. Hosted by The Coding School, in collaboration with universities (including MIT) and tech companies, this two-semester course introduces high schoolers to quantum computing and quantum physics. 

During that time she started a blog called On Zero, representing the “zero state” of a qubit. “The ‘zero state’ in a quantum computer is the representation of creativity from nothing, infinite possibilities,” says Gaul. For the blog, she found different topics and researched them in depth. She would think of a topic or question, such as “What is color?” and then explore it in great detail. What she learned eventually led her to start asking questions such as “What is a hamiltonian?” and teaching quantum physics alongside PhDs.

Building on these interests, Gaul chose to study quantum engineering at the University of New South Wales. She notes that on her first day of university, she participated in iQuHack, the MIT Quantum Hackathon. Her team worked to find a new way to approximate the value of a hyperbolic function using quantum logic, and received an honorable mention for “exceptional creativity.”

Gaul’s passion for making things continued during her college days, especially in terms of innovating to solve a problem. When she found herself on a train, wanting to code a personal website on a computer with a dying battery, she wondered if there might be a way to make a glove that can act as a type of Bluetooth keyboard — essentially creating a way to type in the air. In her spare time, she started working on such a device, ultimately finding a less expensive way to build a lightweight, haptic, gesture-tracking glove with applications for virtual reality (VR) and robotics.

Gaul says she has always had an interest in VR, using it to create her own worlds, reconstruct an old childhood house, and play Dungeons and Dragons with friends. She discovered a way to put into a glove some small linear resonant actuators, which can be found in a smartphone or gaming controller, and map to any object in VR so that the user can feel it.

An early prototype that Gaul put together in her dorm room received a lot of attention on YouTube. She went on to win the People’s Choice award for it at the SxSW Sydney 2025 Tech and Innovation Festival. This design also sparked her co-founding of the tech startup On Zero, named after her childhood blog dedicated to the love of creation from nothing.

Gaul sees the device, in general, as a way of “paying it forward,” making improved human-computer interaction available to many — from young students to professional technologists. She hopes to enable creative freedom in as many as she can. “The mind is just such a fun thing. I want to empower others to have the freedom to follow their curiosity, even if it's pointless on paper.

“I’ve benefited from people going far beyond what they needed to do to help me,” says Gaul. “I see OpenCourseWare as a part of that. The free courses gave me a solid foundation of knowledge and problem-solving abilities. Without these, it wouldn’t be possible to do what I’m doing now.”

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MIT-Hood Pediatric Innovation Hub convenes leaders to advance pediatric health

Facing hospital closures, underfunded pediatric trials, and a persistent reliance on adult-oriented tools for children, the Hood Pediatric Innovation Hub welcomed nearly 200 leaders at Boston’s Museum of Science for MIT-Hood Pediatric Innovation 2025, an event focused on transforming the future of pediatric care through engineering and collaboration.

Hosted by the Hood Pediatric Innovation Hub — established at MIT through a gift by the Hood Foundation — the event brought together attendees from academia, health care, and industry to rethink how medical and technological breakthroughs can reach children faster. The gathering marked a new phase in the hub’s mission to connect scientific discovery with real-world impact.

“We have extraordinary science emerging every day, but the translation gap is widening,” said Joseph Frassica, professor of the practice in MIT’s Institute for Medical Engineering and Science and executive director of the Hood Pediatric Innovation Hub. “We can’t rely on the old model of innovation — we need new connective tissue between ideas, institutions, and implementation.”

Building collaboration across sectors

Speakers emphasized that pediatric medicine has long faced structural disadvantages compared with other fields — from smaller patient populations to limited commercial incentives. Yet they also described a powerful opportunity: to make pediatric innovation a proving ground for smarter, more human-centered health systems.

“The Hood Foundation has always believed that if you can improve care for children, you improve care for everyone,” said Neil Smiley, president of the Charles H. Hood Foundation. “Pediatrics pushes medicine to be smarter, more precise, and more humane — and that’s why this collaboration with MIT feels so right.”

Participants discussed how aligning efforts across universities, hospitals, and industry partners could help overcome the fragmentation that slows innovation, and ultimately translation. Speakers at the event highlighted case studies where cross-sector collaboration is already yielding results — from novel medical devices to data-driven clinical insights.

Connecting discovery to delivery

In his remarks, Elazer R. Edelman, the Edward J. Poitras Professor in Medical Engineering and Science at MIT and faculty lead for the Hood Pediatric Innovation Hub, reflected on how MIT’s engineering and medical communities can help close the loop between research and clinical application.

“This isn’t about creating something new for the sake of it — it’s about finally connecting the extraordinary expertise that already exists, from the lab to the clinic to the child’s bedside,” Edelman said. “That’s what MIT does best — we connect the dots.”

Throughout the day, attendees shared experiences from both the engineering and clinical viewpoints — acknowledging the complexities of regulation, funding, and adoption, while highlighting the shared responsibility to move faster on behalf of children.

A moment of convergence

The conversation also turned to the economics of innovation and the broader societal benefits of investing in pediatric health.

“The economic and social stakes couldn’t be higher,” said Jonathan Gruber, Ford Professor of Economics at MIT. “When we invest in children’s health, we invest in longer lives, stronger communities, and greater prosperity. The energy in this room shows what’s possible when we stop working in silos.”

By the end of the event, discussions had shifted from identifying barriers to designing solutions. Participants explored ideas ranging from translational fellowships and shared data platforms to new models for academic–industry partnership — each aimed at accelerating impact where it is needed most.

Looking ahead

“There’s a feeling that this is the moment,” Frassica said. “We have the tools, the data, and the will to transform how we care for children. The key now is keeping that spirit of collaboration alive — because when we do, we move the whole field forward.”

Building on the momentum from MIT-Hood Pediatric Innovation 2025, the Hood Pediatric Innovation Hub will continue to serve as a connector across disciplines and institutions, advancing projects that translate cutting-edge research into improved outcomes for children everywhere. In January, a new cohort of MIT Catalyst Fellows — early-career researchers embedded with frontline clinicians to identify unmet needs — will begin exploring solutions to challenges in pediatric and neonatal health care in partnership with the hub. 

This work is also part of a wider Institute effort. The Hood Pediatric Innovation Hub contributes to the broader mission of the MIT Health and Life Sciences Collaborative (HEALS), which brings together faculty, clinicians, and industry partners to accelerate breakthroughs across all areas of human health. As the hub deepens its own collaborations, its connection to HEALS helps ensure that advances in pediatric medicine are integrated into MIT’s larger push to improve health outcomes at scale.

The hub will also release a request for proposals in the coming months for the development of its first mentored projects — designed to bring together teams from engineering, medicine, and industry to accelerate progress in children’s health. Updates and details will be available at hoodhub.mit.edu.

As Smiley noted, progress in pediatric health often drives progress across all of medicine — and this gathering underscored that shared belief: when we work together for children, we build a healthier future for everyone.

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New study suggests a way to rejuvenate the immune system

As people age, their immune system function declines. T cell populations become smaller and can’t react to pathogens as quickly, making people more susceptible to a variety of infections.

To try to overcome that decline, researchers at MIT and the Broad Institute have found a way to temporarily program cells in the liver to improve T-cell function. This reprogramming can compensate for the age-related decline of the thymus, where T cell maturation normally occurs.

Using mRNA to deliver three key factors that usually promote T-cell survival, the researchers were able to rejuvenate the immune systems of mice. Aged mice that received the treatment showed much larger and more diverse T cell populations in response to vaccination, and they also responded better to cancer immunotherapy treatments.

If developed for use in patients, this type of treatment could help people lead healthier lives as they age, the researchers say.

“If we can restore something essential like the immune system, hopefully we can help people stay free of disease for a longer span of their life,” says Feng Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT, who has joint appointments in the departments of Brain and Cognitive Sciences and Biological Engineering.

Zhang, who is also an investigator at the McGovern Institute for Brain Research at MIT, a core institute member at the Broad Institute of MIT and Harvard, an investigator in the Howard Hughes Medical Institute, and co-director of the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics at MIT, is the senior author of the new study. Former MIT postdoc Mirco Friedrich is the lead author of the paper, which appears today in Nature.

A temporary factory

The thymus, a small organ located in front of the heart, plays a critical role in T-cell development. Within the thymus, immature T cells go through a checkpoint process that ensures a diverse repertoire of T cells. The thymus also secretes cytokines and growth factors that help T cells to survive.

However, starting in early adulthood, the thymus begins to shrink. This process, known as thymic involution, leads to a decline in the production of new T cells. By the age of approximately 75, the thymus is greatly reduced.

“As we get older, the immune system begins to decline. We wanted to think about how can we maintain this kind of immune protection for a longer period of time, and that's what led us to think about what we can do to boost immunity,” Friedrich says.

Previous work on rejuvenating the immune system has focused on delivering T cell growth factors into the bloodstream, but that can have harmful side effects. Researchers are also exploring the possibility of using transplanted stem cells to help regrow functional tissue in the thymus.

The MIT team took a different approach: They wanted to see if they could create a temporary “factory” in the body that would generate the T-cell-stimulating signals that are normally produced by the thymus.

“Our approach is more of a synthetic approach,” Zhang says. “We're engineering the body to mimic thymic factor secretion.”

For their factory location, they settled on the liver, for several reasons. First, the liver has a high capacity for producing proteins, even in old age. Also, it’s easier to deliver mRNA to the liver than to most other organs of the body. The liver was also an appealing target because all of the body’s circulating blood has to flow through it, including T cells.

To create their factory, the researchers identified three immune cues that are important for T-cell maturation. They encoded these three factors into mRNA sequences that could be delivered by lipid nanoparticles. When injected into the bloodstream, these particles accumulate in the liver and the mRNA is taken up by hepatocytes, which begin to manufacture the proteins encoded by the mRNA.

The factors that the researchers delivered are DLL1, FLT-3, and IL-7, which help immature progenitor T cells mature into fully differentiated T cells.

Immune rejuvenation

Tests in mice revealed a variety of beneficial effects. First, the researchers injected the mRNA particles into 18-month-old mice, equivalent to humans in their 50s. Because mRNA is short-lived, the researchers gave the mice multiple injections over four weeks to maintain a steady production by the liver.

After this treatment, T cell populations showed significant increases in size and function.

The researchers then tested whether the treatment could enhance the animals’ response to vaccination. They vaccinated the mice with ovalbumin, a protein found in egg whites that is commonly used to study how the immune system responds to a specific antigen. In 18-month-old mice that received the mRNA treatment before vaccination, the researchers found that the population of cytotoxic T-cells specific to ovalbumin doubled, compared to mice of the same age that did not receive the mRNA treatment.

The mRNA treatment can also boost the immune system’s response to cancer immunotherapy, the researchers found. They delivered the mRNA treatment to 18-month-old mice, who were then implanted with tumors and treated with a checkpoint inhibitor drug. This drug, which targets the protein PD-L1, is designed to help take the brakes off the immune system and stimulate T cells to attack tumor cells.

Mice that received the treatment showed much higher survival rates and longer lifespan that those that received the checkpoint inhibitor drug but not the mRNA treatment.

The researchers found that all three factors were necessary to induce this immune enhancement; none could achieve all aspects of it on their own. They now plan to study the treatment in other animal models and to identify additional signaling factors that may further enhance immune system function. They also hope to study how the treatment affects other immune cells, including B cells.

Other authors of the paper include Julie Pham, Jiakun Tian, Hongyu Chen, Jiahao Huang, Niklas Kehl, Sophia Liu, Blake Lash, Fei Chen, Xiao Wang, and Rhiannon Macrae.

The research was funded, in part, by the Howard Hughes Medical Institute, the K. Lisa Yang Brain-Body Center, part of the Yang Tan Collective at MIT, Broad Institute Programmable Therapeutics Gift Donors, the Pershing Square Foundation, J. and P. Poitras, and an EMBO Postdoctoral Fellowship.

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Nuno Loureiro, professor and director of MIT’s Plasma Science and Fusion Center, dies at 47

This article may be updated.

Nuno Loureiro, a professor of nuclear science and engineering and of physics at MIT, has died. He was 47.

A lauded theoretical physicist and fusion scientist, and director of the MIT Plasma Science and Fusion Center, Loureiro joined MIT’s faculty in 2016. His research addressed complex problems lurking at the center of fusion vacuum chambers and at the edges of the universe.

Loureiro’s research at MIT advanced scientists’ understanding of plasma behavior, including turbulence, and uncovered the physics behind astronomical phenomena like solar flares. He was the Herman Feshbach (1942) Professor of Physics at MIT and was named director of the Plasma Science and Fusion Center in 2024, though his contributions to fusion science and engineering began far before that.

His research on magnetized plasma dynamics, magnetic field amplification, and confinement and transport in fusion plasmas helped inform the design of fusion devices that could harness the energy of fusing plasmas, bringing the dream of clean, near-limitless fusion power closer to reality.

“Nuno was not only a brilliant scientist, he was a brilliant person,” says Dennis Whyte, the Hitachi America Professor of Engineering, who previously served as the head of the Department of Nuclear Science and Engineering and director of the Plasma Science and Fusion Center. “He shone a bright light as a mentor, friend, teacher, colleague and leader, and was universally admired for his articulate, compassionate manner. His loss is immeasurable to our community at the PSFC, NSE and MIT, and around the entire fusion and plasma research world.”

“Nuno was a champion for plasma physics within the Physics Department, a wonderful and engaging colleague, and an inspiring and caring mentor for graduate students working in plasma science.  His recent work on quantum computing algorithms for plasma physics simulations was a particularly exciting new scientific direction,” says Deepto Chakrabarty, the William A. M. Burden Professor in Astrophysics and head of the Department of Physics.

Whether working on fusion or astrophysics research, Loureiro merged fundamental physics with technology and engineering, to maximize impact.

“There are people who are driven by technology and engineering, and others who are driven by fundamental mathematics and physics. We need both,” Loureiro said in 2019. “When we stimulate theoretically inclined minds by framing plasma physics and fusion challenges as beautiful theoretical physics problems, we bring into the game incredibly brilliant students — people who we want to attract to fusion development.”

Loureiro majored in physics at Instituto Superior Tecnico (IST) in Portugal and obtained a PhD in physics at Imperial College London in 2005. He conducted postdoctoral work at the Princeton Plasma Physics Laboratory for the next two years before moving to the UKAEA Culham Center for Fusion Energy in 2007. Loureiro returned to IST in 2009, where he was a researcher at the Institute for Plasmas and Nuclear Fusion until coming to MIT in 2016.

He wasted no time contributing to the intellectual environment at MIT, spending part of his first two years at the Institute working on the vexing problem of plasma turbulence. Plasma is the super-hot state of matter that serves as the fuel for fusion reactors. Loureiro’s lab at PSFC illuminated how plasma behaves inside fusion reactors, which could help prevent material failures and better contain the plasma to harvest electricity.

“Nuno was not only an extraordinary scientist and educator, but also a tremendous colleague, mentor, and friend who cared deeply about his students and his community. His absence will be felt profoundly across NSE and far beyond,” Benoit Forget, the KEPCO Professor and head of the Department of Nuclear Science and Engineering, wrote in an email to the department today.

On other fronts, Loureiro’s work in astrophysics helped reveal fundamental mechanisms of the universe. He put forward the first theory of turbulence in pair plasmas, which differ from regular plasmas and may be abundant in space. The work was driven, in part, by unprecedented observations of a binary neutron star merger in 2018.

As an assistant professor and then a full professor at MIT, Loureiro taught course 22.612 (Intro to Plasma Physics) and course 22.615 (MHD Theory of Fusion Systems), for which he was twice recognized with the Department of Nuclear Science and Engineering’s PAI Outstanding Professor Award.

Loureiro’s research earned him many prominent awards throughout his prolific career, including the National Science Foundation Career Award and the American Physical Society Thomas H. Stix Award for Outstanding Early Career Contributions to Plasma Physics Research. He was also an APS fellow. Earlier this year, he earned the Presidential Early Career Award for Scientists and Engineers.

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How cement “breathes in” and stores millions of tons of CO₂ a year

The world’s most common construction material has a secret. Cement, the “glue” that holds concrete together, gradually “breathes in” and stores millions of tons of carbon dioxide (CO₂) from the air over the lifetimes of buildings and infrastructure.  

A new study from the MIT Concrete Sustainability Hub quantifies this process, carbon uptake, at a national scale for the first time. Using a novel approach, the research team found that the cement in U.S. buildings and infrastructure sequesters over 6.5 million metric tons of CO₂ annually. This corresponds to roughly 13 percent of the process emissions — the CO₂ released by the underlying chemical reaction — in U.S. cement manufacturing. In Mexico, the same building stock sequesters about 5 million tons a year.   

But how did the team come up with those numbers? 

Scientists have known how carbon uptake works for decades. CO₂ enters concrete or mortar — the mixture that glues together blocks, brick, and stones — through tiny pores, reacts with the calcium-rich products in cement, and becomes locked into a stable mineral called calcium carbonate, or limestone. 

The chemistry is well-known, but calculating the magnitude of this at scale is not. A concrete highway in Dallas sequesters CO₂ differently than Mexico City apartments made from concrete masonry units (CMUs), also called concrete blocks or, colloquially, cinder blocks. And a foundation slab buried under the snow in Fairbanks, Alaska, “breathes in” CO₂ at a different pace entirely. 

As Hessam AzariJafari, lead author and research scientist in the MIT Department of Civil and Environmental Engineering, explains, “Carbon uptake is very sensitive to context. Four major factors drive it: the type of cement used, the product we make with it — concrete, CMUs, or mortar — the geometry of the structure, and the climate and conditions it’s exposed to. Even within the same structure, uptake can vary five-fold between different elements.” 

As no two structures sequester CO₂ in the same way, estimating uptake nationwide would normally require simulating an array of cement-based elements: slabs, walls, beams, columns, pavements, and more. On top of that, each of those has its own age, geometry, mixture, and exposure condition to account for.  

Seeing that this approach would be like trying to count every grain of sand on a beach, the team took a different route. They developed hundreds of archetypes, typical designs that could stand in for different buildings and pieces of infrastructure. It’s a bit like measuring the beach instead by mapping out its shape, depth, and shoreline to estimate how much sand usually sits in a given spot.  

With these archetypes in hand, the team modeled how each one sequesters CO₂ in different environments and how common each is across every state in the United States and Mexico. In this way, they could estimate not just how much CO₂ structures sequester, but why those numbers differ.  

Two factors stood out. The first was the “construction trend,” or how the amount of new construction had changed over the previous five years. Because it reflects how quickly cement products are being added to the building stock, it shapes how much cement each state consumes and, therefore, how much of that cement is actively carbonating. The second was the ratio of mortar to concrete, since porous mortars sequester CO₂ an order of magnitude faster than denser concrete. 

In states where mortar use was higher, the fraction of CO₂ uptake relative to process emissions was noticeably greater. “We observed something unique about Mexico: Despite using half the cement that the U.S. does, the country has three-quarters of the uptake,” notes AzariJafari. “This is because Mexico makes more use of mortars and lower-strength concrete, and bagged cement mixed on-site. These practices are why their uptake sequesters about a quarter of their cement manufacturing emissions.” 

While care must be taken for structural elements that use steel reinforcement, as uptake can accelerate corrosion, it’s possible to enhance the uptake of many elements without negative impacts. 

Randolph Kirchain, director of the MIT Concrete Sustainability Hub, principal research scientist in the MIT Materials Research Laboratory, and the senior author of this study, explains: “For instance, increasing the amount of surface area exposed to air accelerates uptake and can be achieved by foregoing painting or tiling, or choosing designs like waffle slabs with a higher surface area-to-volume ratio. Additionally, avoiding unnecessarily stronger, less-porous concrete mixtures than required would speed up uptake while using less cement.” 

“There is a real opportunity to refine how carbon uptake from cement is represented in national inventories,” AzariJafari comments. “The buildings around us and the concrete beneath our feet are constantly ‘breathing in’ millions of tons of CO₂. Nevertheless, some of the simplified values in widely used reporting frameworks can lead to higher estimates than what we observe empirically. Integrating updated science into international inventories and guidelines such as the Intergovernmental Panel on Climate Change (IPCC) would help ensure that reported numbers reflect the material and temporal realities of the sector.” 

By offering the first rigorous, bottom-up estimation of carbon uptake at a national scale, the team’s work provides a more representative picture of cement’s environmental impact. As we work to decarbonize the built environment, understanding what our structures are already doing in the background may be just as important as the innovations we pursue moving forward. The approach developed by MIT researchers could be extended to other countries by combining global building-stock databases with national cement-production statistics. It could also inform the design of structures that safely maximize uptake. 

The findings were published Dec. 15 in the  Proceedings of the National Academy of Sciences. Joining AzariJafari and Kirchain on the paper are MIT researchers Elizabeth Moore of the Department of Materials Science and Engineering and the MIT Climate Project and former postdocs Ipek Bensu Manav SM ’21, PhD ’24 and Motahareh Rahimi, along with Bruno Huet and Christophe Levy from the Holcim Innovation Center in France.

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A new immunotherapy approach could work for many types of cancer

Researchers at MIT and Stanford University have developed a new way to stimulate the immune system to attack tumor cells, using a strategy that could make cancer immunotherapy work for many more patients.

The key to their approach is reversing a “brake” that cancer cells engage to prevent immune cells from launching an attack. This brake is controlled by sugar molecules known as glycans that are found on the surface of cancer cells.

By blocking those glycans with molecules called lectins, the researchers showed they could dramatically boost the immune system’s response to cancer cells. To achieve this, they created multifunctional molecules known as AbLecs, which combine a lectin with a tumor-targeting antibody.

“We created a new kind of protein therapeutic that can block glycan-based immune checkpoints and boost anti-cancer immune responses,” says Jessica Stark, the Underwood-Prescott Career Development Professor in the MIT departments of Biological Engineering and Chemical Engineering. “Because glycans are known to restrain the immune response to cancer in multiple tumor types, we suspect our molecules could offer new and potentially more effective treatment options for many cancer patients.”

Stark, who is also a member of MIT’s Koch Institute for Integrative Cancer Research, is the lead author of the paper. Carolyn Bertozzi, a professor of chemistry at Stanford and director of the Sarafan ChEM Institute, is the senior author of the study, which appears today in Nature Biotechnology.

Releasing the brakes

Training the immune system to recognize and destroy tumor cells is a promising approach to treating many types of cancer. One class of immunotherapy drugs known as checkpoint inhibitors stimulate immune cells by blocking an interaction between the proteins PD-1 and PD-L1. This removes a brake that tumor cells use to prevent immune cells like T cells from killing cancer cells.

Drugs targeting the PD-1- PD-L1 checkpoint have been approved to treat several kinds of cancer. In some of these patients, checkpoint inhibitors can lead to long-lasting remission, but for many others, they don’t work at all.

In hopes of generating immune responses in a greater number of patients, researchers are now working on ways to target other immunosuppressive interactions between cancer cells and immune cells. One such interaction occurs between glycans on tumor cells and receptors found on immune cells.

Glycans are found on nearly all living cells, but tumor cells often express glycans that are not found on healthy cells, including glycans that contain a monosaccharide called sialic acid. When sialic acids bind to lectin receptors, located on immune cells, it turns on an immunosuppressive pathway in the immune cells. These lectins that bind to sialic acid are known as Siglecs.

“When Siglecs on immune cells bind to sialic acids on cancer cells, it puts the brakes on the immune response. It prevents that immune cell from becoming activated to attack and destroy the cancer cell, just like what happens when PD-1 binds to PD-L1,” Stark says.

Currently, there aren’t any approved therapies that target this Siglec-sialic acid interaction, despite a number of drug development approaches that have been tried. For example, researchers have tried to develop lectins that could bind to sialic acids and prevent them from interacting with immune cells, but so far, this approach hasn’t worked well because lectins don’t bind strongly enough to accumulate on the cancer cell surface in large numbers.

To overcome that, Stark and her colleagues developed a way to deliver larger quantities of lectins by attaching them to antibodies that target cancer cells. Once there, the lectins can bind to sialic acid, preventing sialic acid from interacting with Siglec receptors on immune cells. This lifts the brakes off the immune response, allowing immune cells such as macrophages and natural killer (NK) cells to launch an attack on the tumor.

“This lectin binding domain typically has relatively low affinity, so you can’t use it by itself as a therapeutic. But, when the lectin domain is linked to a high-affinity antibody, you can get it to the cancer cell surface where it can bind and block sialic acids,” Stark says.

A modular system

In this study, the researchers designed an AbLec based on the antibody trastuzumab, which binds to HER2 and is approved as a cancer therapy to treat breast, stomach, and colorectal cancers. To form the AbLec, they replaced one arm of the antibody with a lectin, either Siglec-7 or Siglec-9.

Tests using cells grown in the lab showed that this AbLec rewired immune cells to attack and destroy cancer cells.

The researchers then tested their AbLecs in a mouse model that was engineered to express human Siglec receptors and antibody receptors. These mice were then injected with cancer cells that formed metastases in the lungs. When treated with the AbLec, these mice showed fewer lung metastases than mice treated with trastuzumab alone.

The researchers also showed that they could swap in other tumor-specific antibodies, such as rituximab, which targets CD20, or cetuximab, which targets EGFR. They could also swap in lectins that target other glycans involved in immunosuppression, or antibodies that target checkpoint proteins such as PD-1.

“AbLecs are really plug-and-play. They’re modular,” Stark says. “You can imagine swapping out different decoy receptor domains to target different members of the lectin receptor family, and you can also swap out the antibody arm. This is important because different cancer types express different antigens, which you can address by changing the antibody target.”

Stark, Bertozzi, and others have started a company called Valora Therapeutics, which is now working on developing lead AbLec candidates. They hope to begin clinical trials in the next two to three years.

The research was funded, in part, by a Burroughs Wellcome Fund Career Award at the Scientific Interface, a Society for Immunotherapy of Cancer Steven A. Rosenberg Scholar Award, a V Foundation V Scholar Grant, the National Cancer Institute, the National Institute of General Medical Sciences, a Merck Discovery Biologics SEEDS grant, an American Cancer Society Postdoctoral Fellowship, and a Sarafan ChEM-H Postdocs at the Interface seed grant.

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“Robot, make me a chair”

Computer-aided design (CAD) systems are tried-and-true tools used to design many of the physical objects we use each day. But CAD software requires extensive expertise to master, and many tools incorporate such a high level of detail they don’t lend themselves to brainstorming or rapid prototyping.

In an effort to make design faster and more accessible for non-experts, researchers from MIT and elsewhere developed an AI-driven robotic assembly system that allows people to build physical objects by simply describing them in words.

Their system uses a generative AI model to build a 3D representation of an object’s geometry based on the user’s prompt. Then, a second generative AI model reasons about the desired object and figures out where different components should go, according to the object’s function and geometry.

The system can automatically build the object from a set of prefabricated parts using robotic assembly. It can also iterate on the design based on feedback from the user.

The researchers used this end-to-end system to fabricate furniture, including chairs and shelves, from two types of premade components. The components can be disassembled and reassembled at will, reducing the amount of waste generated through the fabrication process.

They evaluated these designs through a user study and found that more than 90 percent of participants preferred the objects made by their AI-driven system, as compared to different approaches.

While this work is an initial demonstration, the framework could be especially useful for rapid prototyping complex objects like aerospace components and architectural objects. In the longer term, it could be used in homes to fabricate furniture or other objects locally, without the need to have bulky products shipped from a central facility.

“Sooner or later, we want to be able to communicate and talk to a robot and AI system the same way we talk to each other to make things together. Our system is a first step toward enabling that future,” says lead author Alex Kyaw, a graduate student in the MIT departments of Electrical Engineering and Computer Science (EECS) and Architecture.

Kyaw is joined on the paper by Richa Gupta, an MIT architecture graduate student; Faez Ahmed, associate professor of mechanical engineering; Lawrence Sass, professor and chair of the Computation Group in the Department of Architecture; senior author Randall Davis, an EECS professor and member of the Computer Science and Artificial Intelligence Laboratory (CSAIL); as well as others at Google Deepmind and Autodesk Research. The paper was recently presented at the Conference on Neural Information Processing Systems.

Generating a multicomponent design

While generative AI models are good at generating 3D representations, known as meshes,  from text prompts, most do not produce uniform representations of an object’s geometry that have the component-level details needed for robotic assembly.

Separating these meshes into components is challenging for a model because assigning components depends on the geometry and functionality of the object and its parts.

The researchers tackled these challenges using a vision-language model (VLM), a powerful generative AI model that has been pre-trained to understand images and text. They task the VLM with figuring out how two types of prefabricated parts, structural components and panel components, should fit together to form an object.

“There are many ways we can put panels on a physical object, but the robot needs to see the geometry and reason over that geometry to make a decision about it. By serving as both the eyes and brain of the robot, the VLM enables the robot to do this,” Kyaw says.

A user prompts the system with text, perhaps by typing “make me a chair,” and gives it an AI-generated image of a chair to start.

Then, the VLM reasons about the chair and determines where panel components go on top of structural components, based on the functionality of many example objects it has seen before. For instance, the model can determine that the seat and backrest should have panels to have surfaces for someone sitting and leaning on the chair.

It outputs this information as text, such as “seat” or “backrest.” Each surface of the chair is then labeled with numbers, and the information is fed back to the VLM.

Then the VLM chooses the labels that correspond to the geometric parts of the chair that should receive panels on the 3D mesh to complete the design.

Human-AI co-design

The user remains in the loop throughout this process and can refine the design by giving the model a new prompt, such as “only use panels on the backrest, not the seat.”

“The design space is very big, so we narrow it down through user feedback. We believe this is the best way to do it because people have different preferences, and building an idealized model for everyone would be impossible,” Kyaw says.

“The human‑in‑the‑loop process allows the users to steer the AI‑generated designs and have a sense of ownership in the final result,” adds Gupta.

Once the 3D mesh is finalized, a robotic assembly system builds the object using prefabricated parts. These reusable parts can be disassembled and reassembled into different configurations.

The researchers compared the results of their method with an algorithm that places panels on all horizontal surfaces that are facing up, and an algorithm that places panels randomly. In a user study, more than 90 percent of individuals preferred the designs made by their system.

They also asked the VLM to explain why it chose to put panels in those areas.

“We learned that the vision language model is able to understand some degree of the functional aspects of a chair, like leaning and sitting, to understand why it is placing panels on the seat and backrest. It isn’t just randomly spitting out these assignments,” Kyaw says.

In the future, the researchers want to enhance their system to handle more complex and nuanced user prompts, such as a table made out of glass and metal. In addition, they want to incorporate additional prefabricated components, such as gears, hinges, or other moving parts, so objects could have more functionality.

“Our hope is to drastically lower the barrier of access to design tools. We have shown that we can use generative AI and robotics to turn ideas into physical objects in a fast, accessible, and sustainable manner,” says Davis.

de MIT News https://ift.tt/LAhHpeM