Taking an audience of hundreds on a tour around the body, seven speakers at The Picower Institute for Learning and Memory’s symposium “Circuits of Survival and Homeostasis” Oct. 21 shared their advanced and novel research about some of the nervous system’s most evolutionarily ancient functions.

Introducing the symposium that she arranged with a picture of a man at a campfire on a frigid day, Sara Prescott, assistant professor in the Picower Institute and MIT’s departments of Biology and Brain and Cognitive Sciences, pointed out that the brain and the body cooperate constantly just to keep us going, and that when the systems they maintain fail, the consequence is disease.

“[This man] is tightly regulating his blood pressure, glucose levels, his energy expenditure, inflammation and breathing rate, and he’s doing this in the face of a fluctuating external environment,” Prescott said. “Behind each of these processes there are networks of neurons that are working quietly in the background to maintain internal stability. And this is, of course, the brain’s oldest job.”

Indeed, although the discoveries they shared about the underlying neuroscience were new, the speakers each described experiences that are as timeless as they are familiar: the beating of the heart, the transition from hunger to satiety, and the healing of cuts on our skin.

Feeling warm and full

Li Ye, a scientist at Scripps Research, picked right up on the example of coping with the cold. Mammals need to maintain a consistent internal body temperature, and so they will increase metabolism in the cold and then, as energy supplies dwindle, seek out more food. His lab’s 2023 study identified the circuit, centered in the Xiphoid nucleus of the brain’s thalamus, that regulates this behavior by sensing prolonged cold exposure and energy consumption. Ye described other feeding mechanisms his lab is studying as well, including searching out the circuitry that regulates how long an animal will feed at a time. For instance, if you’re worried about predators finding you, it’s a bad idea to linger for a leisurely lunch.

Physiologist Zachary Knight of the University of California at San Francisco also studies feeding and drinking behaviors. In particular, his lab asks how the brain knows when it’s time to stop. The conventional wisdom is that all that’s needed is a feeling of fullness coming from the gut, but his research shows there is more to the story. A 2023 study from his lab found a population of neurons in the caudal nucleus of the solitary tract in the brain stem that receive signals about ingestion and taste from the mouth, and that send that “stop eating” signal. They also found a separate neural population in the brain stem that indeed receives fullness signals from the gut, and teaches the brain over time how much food leads to satisfaction. Both neuron types work together to regulate the pace of eating. His lab has continued to study how brain stem circuits regulate feeding using these multiple inputs.

Energy balance depends not only on how many calories come in, but also on how much energy is spent. When food is truly scarce, many animals will engage in a state of radically lowered metabolism called torpor (like hibernation), where body temperature plummets. The brain circuits that exert control over body temperature are another area of active research. In his talk, Harvard University neurologist Clifford Saper described years of research in which his lab found neurons in the median preoptic nucleus that dictate this metabolic state. Recently, his lab demonstrated that the same neurons that regulate torpor also regulate fever during sickness. When the neurons are active, body temperature drops. When they are inhibited, fever ensues. Thus, the same neurons act as a two-way switch for body temperature in response to different threatening conditions.

Sickness, injury, and stress

As the idea of fever suggests, the body also has evolved circuits (that scientists are only now dissecting) to deal with sickness and injury.

Washington University neuroscientist Qin Liu described her research into the circuits governing coughing and sneezing, which, on one hand, can clear the upper airways of pathogens and obstructions but, on the other hand, can spread those pathogens to others in the community. She described her lab’s 2024 study in which her team pinpointed a population of neurons in the nasal passages that mediate sneezing and a different population of sensory neurons in the trachea that produce coughing. Identifying the specific cells and their unique characteristics makes them potentially viable drug targets.

While Liu tackled sickness, Harvard stem cell biologist Ya-Chieh Hsu discussed how neurons can reshape the body’s tissues during stress and injury, specifically the hair and skin. While it is common lore that stress can make your hair gray and fall out, Hsu’s lab has shown the actual physiological mechanisms that make it so. In 2020 her team showed that bursts of noradrenaline from the hyperactivation of nerves in the sympathetic nervous system kills the melanocyte stem cells that give hair its color. She described newer research indicating a similar mechanism may also make hair fall out by killing off cells at the base of hair follicles, releasing cellular debris and triggering auto-immunity. Her lab has also looked at how the nervous system influences skin healing after injury. For instance, while our skin may appear to heal after a cut because it closes up, many skin cell types actually don’t rebound (unless you’re still an embryo). By looking at the difference between embryos and post-birth mice, Hsu’s lab has traced the neural mechanisms that prevent fuller healing, identifying a role for cells called fibroblasts and the nervous system.

Continuing on the theme of stress, Caltech biologist Yuki Oka discussed a broad-scale project in his lab to develop a molecular and cellular atlas of the sympathetic nervous system, which innervates much of the body and famously produces its “fight or flight” responses. In work partly published last year, their journey touched on cells and circuits involved in functions ranging from salivation to secreting bile. Oka and co-authors made the case for the need to study the system more in a review paper earlier this year.

A new model to study human biology

In their search for the best ways to understand the circuits that govern survival and homeostasis, researchers often use rodents because they are genetically tractable, easy to house, and reproduce quickly, but Stanford University biochemist Mark Krasnow has worked to develop a new model with many of those same traits but a closer genetic relationship to humans: the mouse lemur. In his talk, he described that work (which includes extensive field research in Madagascar) and focused on insights the mouse lemurs have helped him make into heart arrhythmias. After studying the genes and health of hundreds of mouse lemurs, his lab identified a family with “sick sinus syndrome,” an arrhythmia also seen in humans. In a preprint study, his lab describes the specific molecular pathways at fault in disrupting the heart’s natural pace making.

By sharing some of the latest research into how the brain and body work to stay healthy, the symposium’s speakers highlighted the most current thinking about the nervous system’s most primal purposes.

Ernest Opoku knew he wanted to become a scientist when he was a little boy. But his school in Dadease, a small town in Ghana, offered no elective science courses — so Opoku created one for himself.

Even though they had neither a dedicated science classroom nor a lab, Opoku convinced his principal to bring in someone to teach him and five other friends he had convinced to join him. With just a chalkboard and some imagination, they learned about chemical interactions through the formulas and diagrams they drew together.

“I grew up in a town where it was difficult to find a scientist,” he says.

Today, Opoku has become one himself, recently earning a PhD in quantum chemistry from Auburn University. This year, he joins MIT as a part of the School of Science Dean’s Postdoctoral Fellowship program. Working with the Van Voorhis Group at the Department of Chemistry, Opoku’s goal is to advance computational methods to study how electrons behave — a fundamental research that underlies applications ranging from materials science to drug discovery.

“As a boy who wanted to satisfy my own curiosities at a young age, in addition to the fact that my parents had minimal formal education,” Opoku says, “I knew that the only way I would be able to accomplish my goal was to work hard.”

In pursuit of knowledge

When Opoku was 8 years old, he began independently learning English at school. He would come back with homework, but his parents were unable to help him, as neither of them could read or write in English. Frustrated, his mother asked an older student to help tutor her son.

Every day, the boys would meet at 6 o’clock. With no electricity at either of their homes, they practiced new vocabulary and pronunciations together by a kerosene lamp.

As he entered junior high school, Opoku’s fascination with nature grew.

“I realized that chemistry was the central science that really offered the insight that I wanted to really understand Creation from the smallest level,” he says.

He studied diligently and was able to get into one of Ghana’s top high schools — but his parents couldn’t afford the tuition. He therefore enrolled in Dadease Agric Senior High School in his hometown. By growing tomatoes and maize, he saved up enough money to support his education.

In 2012, he got into Kwame Nkrumah University of Science and Technology (KNUST), a first-ranking university in Ghana and the West Africa region. There, he was introduced to computational chemistry. Unlike many other branches of science, the field required only a laptop and the internet to study chemical reactions.

“Anything that comes to mind, anytime I can grab my computer and I’ll start exploring my curiosity. I don’t have to wait to go to the laboratory in order to interrogate nature,” he says.

Opoku worked from early morning to late night. None of it felt like work, though, thanks to his supervisor, the late quantum chemist Richard Tia, who was an associate professor of chemistry at KNUST.

“Every single day was a fun day,” he recalls of his time working with Tia. “I was being asked to do the things that I myself wanted to know, to satisfy my own curiosity, and by doing that I’ll be given a degree.”

In 2020, Opoku’s curiosity brought him even further, this time overseas to Auburn University in Alabama for his PhD. Under the guidance of his advisor, Professor J. V. Ortiz, Opoku contributed to the development of new computational methods to simulate how electrons bind to or detach from molecules, a process known as electron propagation.

What is new about Opoku’s approach is that it does not rely on any adjustable or empirical parameters. Unlike some earlier computational methods that require tuning to match experimental results, his technique uses advanced mathematical formulations to directly account for first principles of electron interactions. This makes the method more accurate — closely resembling results from lab experiments — while using less computational power.

By streamlining the calculations and eliminating guesswork, Opoku’s work marks a major step toward faster, more trustworthy quantum simulations across a wide range of molecules, including those never studied before — laying the groundwork for breakthroughs in many areas such as materials science and sustainable energy.

For his postdoctoral research at MIT, Opoku aims to advance electron propagator methods to address larger and more complex molecules and materials by integrating quantum computing, machine learning, and bootstrap embedding — a technique that simplifies quantum chemistry calculations by dividing large molecules into smaller, overlapping fragments. He is collaborating with Troy Van Voorhis, the Haslam and Dewey Professor of Chemistry, whose expertise in these areas can help make Opoku’s advanced simulations more computationally efficient and scalable.

“His approach is different from any of the ways that we've pursued in the group in the past,” Van Voorhis says.

Passing along the opportunity to learn

Opoku thanks previous mentors who helped him overcome the “intellectual overhead required to make contributions to the field,” and believes Van Voorhis will offer the same kind of support.

In 2021, Opoku joined the National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) to gain mentorship, networking, and career development opportunities within a supportive community. He later led the Auburn University chapter as president, helping coordinate k-12 outreach to inspire the next generation of scientists, engineers, and innovators.

“Opoku’s mentorship goes above and beyond what would be typical at his career stage,” says Van Voorhis. “One reason is his ability to communicate science to people, and not just the concepts of science, but also the process of science."

Back home, Opoku founded the Nesvard Institute of Molecular Sciences to support African students to develop not only skills for graduate school and professional careers, but also a sense of confidence and cultural identity. Through the nonprofit, he has mentored 29 students so far, passing along the opportunity for them to follow their curiosity and help others do the same.

“There are many areas of science and engineering to which Africans have made significant contributions, but these contributions are often not recognized, celebrated, or documented,” Opoku says.

He adds: “We have a duty to change the narrative.” 

Computer-Aided Design (CAD) is the go-to method for designing most of today’s physical products. Engineers use CAD to turn 2D sketches into 3D models that they can then test and refine before sending a final version to a production line. But the software is notoriously complicated to learn, with thousands of commands to choose from. To be truly proficient in the software takes a huge amount of time and practice.

MIT engineers are looking to ease CAD’s learning curve with an AI model that uses CAD software much like a human would. Given a 2D sketch of an object, the model quickly creates a 3D version by clicking buttons and file options, similar to how an engineer would use the software.

The MIT team has created a new dataset called VideoCAD, which contains more than 41,000 examples of how 3D models are built in CAD software. By learning from these videos, which illustrate how different shapes and objects are constructed step-by-step, the new AI system can now operate CAD software much like a human user.

With VideoCAD, the team is building toward an AI-enabled “CAD co-pilot.” They envision that such a tool could not only create 3D versions of a design, but also work with a human user to suggest next steps, or automatically carry out build sequences that would otherwise be tedious and time-consuming to manually click through.

“There’s an opportunity for AI to increase engineers’ productivity as well as make CAD more accessible to more people,” says Ghadi Nehme, a graduate student in MIT’s Department of Mechanical Engineering.

“This is significant because it lowers the barrier to entry for design, helping people without years of CAD training to create 3D models more easily and tap into their creativity,” adds Faez Ahmed, associate professor of mechanical engineering at MIT.

Ahmed and Nehme, along with graduate student Brandon Man and postdoc Ferdous Alam, will present their work at the Conference on Neural Information Processing Systems (NeurIPS) in December.

Click by click

The team’s new work expands on recent developments in AI-driven user interface (UI) agents — tools that are trained to use software programs to carry out tasks, such as automatically gathering information online and organizing it in an Excel spreadsheet. Ahmed’s group wondered whether such UI agents could be designed to use CAD, which encompasses many more features and functions, and involves far more complicated tasks than the average UI agent can handle.

In their new work, the team aimed to design an AI-driven UI agent that takes the reins of the CAD program to create a 3D version of a 2D sketch, click by click. To do so, the team first looked to an existing dataset of objects that were designed in CAD by humans. Each object in the dataset includes the sequence of high-level design commands, such as “sketch line,” “circle,” and “extrude,” that were used to build the final object.

However, the team realized that these high-level commands alone were not enough to train an AI agent to actually use CAD software. A real agent must also understand the details behind each action. For instance: Which sketch region should it select? When should it zoom in? And what part of a sketch should it extrude? To bridge this gap, the researchers developed a system to translate high-level commands into user-interface interactions.

“For example, let’s say we drew a sketch by drawing a line from point 1 to point 2,” Nehme says. “We translated those high-level actions to user-interface actions, meaning we say, go from this pixel location, click, and then move to a second pixel location, and click, while having the ‘line’ operation selected.”

In the end, the team generated over 41,000 videos of human-designed CAD objects, each of which is described in real-time in terms of the specific clicks, mouse-drags, and other keyboard actions that the human originally carried out. They then fed all this data into a model they developed to learn connections between UI actions and CAD object generation.

Once trained on this dataset, which they dub VideoCAD, the new AI model could take a 2D sketch as input and directly control the CAD software, clicking, dragging, and selecting tools to construct the full 3D shape. The objects ranged in complexity from simple brackets to more complicated house designs. The team is training the model on more complex shapes and envisions that both the model and the dataset could one day enable CAD co-pilots for designers in a wide range of fields.

“VideoCAD is a valuable first step toward AI assistants that help onboard new users and automate the repetitive modeling work that follows familiar patterns,” says Mehdi Ataei, who was not involved in the study, and is a senior research scientist at Autodesk Research, which develops new design software tools. “This is an early foundation, and I would be excited to see successors that span multiple CAD systems, richer operations like assemblies and constraints, and more realistic, messy human workflows.”

If there was one thing Cameron Halliday SM ’19, MBA ’22, PhD ’22 was exceptional at during the early days of his PhD at MIT, it was producing the same graph over and over again. Unfortunately for Halliday, the graph measured various materials’ ability to absorb CO2 at high temperatures over time — and it always pointed down and to the right. That meant the materials lost their ability to capture the molecules responsible for warming our climate.

At least Halliday wasn’t alone: For many years, researchers have tried and mostly failed to find materials that could reliably absorb CO2 at the super-high temperatures of industrial furnaces, kilns, and boilers. Halliday’s goal was to find something that lasted a little longer.

Then in 2019, he put a type of molten salt called lithium-sodium ortho-borate through his tests. The salts absorbed more than 95 percent of the CO2. And for the first time, the graph showed almost no degradation over 50 cycles.  The same was true after 100 cycles. Then 1,000.

“I honestly don’t know if we ever expected to completely solve the problem,” Halliday says. “We just expected to improve the system. It took another two months to figure out why it worked.”

The researchers discovered the salts behave like a liquid at high temperatures, which avoids the brittle cracking responsible for the degradation of many solid materials.

“I remember walking home over the Mass Ave bridge at 5 a.m. with all the morning runners going by me,” Halliday recalls. “That was the moment when I realized what this meant. Since then, it’s been about proving it works at larger scales. We’ve just been building the next scaled-up version, proving it still works, building a bigger version, proving that out, until we reach the ultimate goal of deploying this everywhere.”

Today, Halliday is the co-founder and CEO of Mantel, a company building systems to capture carbon dioxide at large industrial sites of all types. Although a lot of people think the carbon capture industry is a dead end, Halliday doesn’t give up so easily, and he’s got a growing corpus of performance data to keep him encouraged.

Mantel’s system can be added on to the machines of power stations and factories making cement, steel, paper and pulp, oil and gas, and more, reducing their carbon emissions by around 95 percent. Instead of being released into the atmosphere, the emitted CO2 is channeled into Mantel’s system, where the company’s salts are sprayed out from something that looks like a shower head. The CO2 diffuses through the molten salts in a reaction that can be reversed through further temperature increases, so the salts boil off pure CO2 that can be transported for use or stored underground.

A key difference from other carbon capture methods that have struggled to be profitable is that Mantel uses the heat from its process to generate steam for customers by combining it with water in another part of its system. Mantel says delivering steam, which is used to drive many common industrial processes, lets its system work with just 3 percent of the net energy that state-of-the-art carbon capture systems require.

“We’re still consuming energy, but we get most of it back as steam, whereas the incumbent technology only consumes steam,” says Halliday, who co-founded Mantel with Sean Robertson PhD ’22 and Danielle Rapson. “That steam is a useful revenue stream, so we can turn carbon capture from a waste management process into a value creation process for our customer’s core business — whether that’s a power station using steam to make electricity, or oil and gas refineries. It completely changes the economics of carbon capture.”

From science to startup

Halliday’s first exposure to MIT came in 2016 when he cold emailed Alan Hatton, MIT’s Ralph Landau Professor of Chemical Engineering Practice, asking if he could come to his lab for the summer and work on research into carbon capture.

“He invited me, but he didn’t put me on that project,” Halliday recalls. “At the end of the summer he said, ‘You should consider coming back and doing a PhD.’”

Halliday enrolled in a joint PhD-MBA program the following year.

“I really wanted to work on something that had an impact,” Halliday says. “The dual PhD-MBA program has some deep technical academic elements to it, but you also work with a company for two months, so you use a lot of what you learn in the real world.”

Halliday worked on a few different research projects in Hatton’s lab early on, all three of which eventually turned into companies. The one that he stuck with explored ways to make carbon capture more energy efficient by working at the high temperatures common at emissions-heavy industrial sites.

Halliday ran into the same problems as past researchers with materials degrading at such extreme conditions.

“It was the big limiter for the technology,” Halliday recalls.

Then Halliday ran his successful experiment with molten borate salts in 2019. The MBA portion of his program began soon after, and Halliday decided to use that time to commercialize the technology. Part of that occurred in Course 15.366 (Climate and Energy Ventures), where Halliday met his co-founders. As it happens, alumni of the class have started more than 150 companies over the years.

“MIT tries to pull these great ideas out of academia and get them into the world so they can be valued and used,” Halliday says. “For the Climate and Energy Ventures class, outside speakers showed us every stage of company-building. The technology roadmap for our system is shoebox-sized, shipping container, one-bedroom house, and then the size of a building. It was really valuable to see other companies and say, ‘That’s what we could look like in three years, or six years.”

From startup to scale up

When Mantel was officially founded in 2022 the founders had their shoebox-sized system. After raising early funding, the team built its shipping container-sized system at The Engine, an MIT-affiliated startup incubator. That system has been operational for almost two years.

Last year, Mantel announced a partnership with Kruger Inc. to build the next version of its system at a factory in Quebec, which will be operational next year. The plant will run in a two-year test phase before scaling across Kruger’s other plants if successful.

“The Quebec project is proving the capture efficiency and proving the step-change improvement in energy use of our system,” Halliday says. “It’s a derisking of the technology that will unlock a lot more opportunities.”

Halliday says Mantel is in conversations with close to 100 industrial partners around the world, including the owners of refineries, data centers, cement and steel plants, and oil and gas companies. Because it’s a standalone addition, Halliday says Mantel’s system doesn’t have to change much to be used in different industries.

Mantel doesn’t handle CO2 conversion or sequestration, but Halliday says capture makes up the bulk of the costs in the CO2 value chain. It also generates high-quality CO2 that can be transported in pipelines and used in industries including the food and beverage industry — like the CO2 that makes your soda bubbly.

“This is the solution our customers are dreaming of,” Halliday says. “It means they don’t have to shut down their billion-dollar asset and reimagine their business to address an issue that they all appreciate is existential. There are questions about the timeline, but most industries recognize this is a problem they’ll have to grapple with eventually. This is a pragmatic solution that’s not trying to reshape the world as we dream of it. It’s looking at the problem at hand today and fixing it.”