Exploring interactions of light and matter

Growing up in a small town in Fujian province in southern China, Juejun Hu was exposed to engineering from an early age. His father, trained as a mechanical engineer, spent his career working first in that field, then in electrical engineering, and then civil engineering.

“He gave me early exposure to the field. He brought me books and told me stories of interesting scientists and scientific activities,” Hu recalls. So when it came time to go to college — in China students have to choose their major before enrolling — he picked materials science, figuring that field straddled his interests in science and engineering. He pursued that major at Tsinghua University in Beijing.

He never regretted that decision. “Indeed, it’s the way to go,” he says. “It was a serendipitous choice.” He continued on to a doctorate in materials science at MIT, and then spent four and a half years as an assistant professor at the University of Delaware before joining the MIT faculty. Last year, Hu earned tenure as an associate professor in MIT’s Department of Materials Science and Engineering.

In his work at the Institute, he has focused on optical and photonic devices, whose applications include improving high-speed communications, observing the behavior of molecules, designing better medical imaging systems, and developing innovations in consumer electronics such as display screens and sensors.

“I got fascinated with light,” he says, recalling how he began working in this field. “It has such a direct impact on our lives.”

Hu is now developing devices to transmit information at very high rates, for data centers or high-performance computers. This includes work on devices called optical diodes or optical isolators, which allow light to pass through only in one direction, and systems for coupling light signals into and out of photonic chips.

Lately, Hu has been focusing on applying machine-learning methods to improve the performance of optical systems. For example, he has developed an algorithm that improves the sensitivity of a spectrometer, a device for analyzing the chemical composition of materials based on how they emit or absorb different frequencies of light. The new approach made it possible to shrink a device that ordinarily requires bulky and expensive equipment down to the scale of a computer chip, by improving its ability to overcome random noise and provide a clean signal.

The miniaturized spectrometer makes it possible to analyze the chemical composition of individual molecules with something “small and rugged, to replace devices that are large, delicate, and expensive,” he says.

Much of his work currently involves the use of metamaterials, which don’t occur in nature and are synthesized usually as a series of ultrathin layers, so thin that they interact with wavelengths of light in novel ways. These could lead to components for biomedical imaging, security surveillance, and sensors on consumer electronics, Hu says. Another project he’s been working on involved developing a kind of optical zoom lens based on metamaterials, which uses no moving parts.

Hu is also pursuing ways to make photonic and photovoltaic systems that are flexible and stretchable rather than rigid, and to make them lighter and more compact. This could  allow for installations in places that would otherwise not be practical. “I’m always looking for new designs to start a new paradigm in optics, [to produce] something that’s smaller, faster, better, and lower cost,” he says.

Hu says the focus of his research these days is mostly on amorphous materials — whose atoms are randomly arranged as opposed to the orderly lattices of crystal structures — because crystalline materials have been so well-studied and understood. When it comes to amorphous materials, though, “our knowledge is amorphous,” he says. “There are lots of new discoveries in the field.”

Hu’s wife, Di Chen, whom he met when they were both in China, works in the financial industry. They have twin daughters, Selena and Eos, who are 1 year old, and a son Helius, age 3. Whatever free time he has, Hu says, he likes to spend doing things with his kids.

Recalling why he was drawn to MIT, he says, “I like this very strong engineering culture.” He especially likes MIT’s strong system of support for bringing new advances out of the lab and into real-world application. “This is what I find really useful.” When new ideas come out of the lab, “I like to see them find real utility,” he adds.

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MIT Prison Education Program documentary wins New England Emmy Award

A short documentary featuring MIT’s Prison Education Program received an Emmy Award from the New England Chapter of the National Academy of Television Arts and Sciences at its virtual award ceremony on June 20. Produced by WGBH, the film bested five other nominees in the Education/Schools category.

“Redemption: MIT’s Prison Education Program” is an intimate portrait of a class discussion that took place last November, part of philosophy course ES.9114 (Nonviolence as a Way of Life). Taught by Lee Perlman, lecturer and co-director of the MIT Educational Justice Institute (TEJI), the course enrollment included a small cohort of what Perlman calls “outside” students — 10 MIT undergraduates — and an equal number of “inside” students: youthful offenders at Boston’s South Bay House of Correction. On this particular autumn day, students gathered at the prison to discuss the topic of forgiveness.

“The documentary beautifully captures the humanity of the incarcerated students, and the wonderful human connections between MIT students and the incarcerated people — mostly around their age  —who are working hard to turn their lives around,” says Perlman. “At one point in the film, an older incarcerated man lovingly gives advice to a young MIT student about some problems in his family. It shows how coming together on an equal footing allows people from very different backgrounds to learn from each other.”

“The film does a wonderful job illustrating the power of education to serve as a point of communication, understanding, and a degree of equality between students on either side of the wall,” adds Carole Cafferty, co-director of TEJI. “Co-learning models like this speak to our shared humanity and limitless capacity for change, even in the face of challenging circumstances.”

Although the documentary focuses on one particular discussion, “these are real academic classes with college credit, and the incarcerated students also do readings and papers,” notes Perlman.

The course is just one example of TEJI’s programs, which aim to provide unique co-learning opportunities for students inside and outside of correctional facilities. Since its inception in 2017, the initiative has grown by leaps and bounds: in 2018, TEJI established the Massachusetts Prison Education Consortium, comprised of 50 colleges, universities, and other organizations invested in reducing barriers to post-secondary education for those in the criminal justice system.

Research indicates that these efforts can have a dramatic impact: according to a 2013 RAND Corporation study, inmates who experienced post-secondary education are 43 percent less likely to return to prison.

WGBH producers Meghan Smith and Greg Shea approached TEJI in fall 2019 about the project. Inspired by the Ken Burns documentary “College Behind Bars,” they wanted to highlight a local postsecondary education program for incarcerated students.

“When I discovered that Lee not only teaches inside a Boston prison, but he also brings MIT students with him, I knew that would be a fascinating story to tell,” Smith says. “I was also drawn to the fact that Lee teaches subjects like nonviolence and forgiveness. From both student groups, I knew that hearing discussions like that would be interesting — for the ‘outside’ MIT students, since they are the brightest scientific minds I guessed those topics would be novel, and also the ‘inside’ students, who bring a very different perspective to those conversations, since they have such different life experiences.”

Smith found the project moving and inspiring — particularly how honest and open the incarcerated students were about their experiences, “even while we had cameras in their faces,” she says. “Also, I think this program is an example of how powerful institutions like MIT can use their resources to serve social justice causes.”

Perlman and Cafferty are deeply grateful to Smith, Shea, and WGBH for shining a spotlight on the program and hope the film will draw attention to the transformational power of prison education reform.

“This award provides further validation that this story, and successful rehabilitation and re-entry efforts, are not limited to an isolated community but rather are vital issues that society at large should be aware of and invested in,” says Cafferty.

“We are ushering in a statewide renaissance of college in prison, and the documentary will be a great boost to our efforts,” adds Perlman.

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How worms move: Dopamine helps nematodes coordinate motor behaviors

For a nematode worm, a big lawn of the bacteria that it eats is a great place for it to disperse its eggs so that each hatchling can emerge into a nutritive environment. That’s why when a worm speedily roams about a food patch, it methodically lays its eggs as it goes. A new study by neuroscientists at MIT’s Picower Institute for Learning and Memory investigates this example of action coordination — where egg-laying is coupled to the animal’s roaming — to demonstrate how a nervous system coordinates distinct behavioral outputs. That’s a challenge many organisms face, albeit in different ways, during daily life.

“All animals display a remarkable ability to coordinate their diverse motor programs, but the mechanisms within the brain that allow for this coordination are poorly understood,” note the scientists, including Steven Flavell, Lister Brothers Career Development Assistant Professor in MIT’s Department of Brain and Cognitive Sciences.

Flavell lab members Nathan Cermak, Stephanie Yu, and Rebekah Clark were co-lead authors of the study published this month in eLife.

A new imaging platform

To learn how animals coordinate their motor programs, Flavell’s team invented a new microscopy platform capable of taking sharp, high-frame-rate videos of nematodes for hours or days on end. Guided by custom software, the scope automatically tracks the worms, allowing the researchers to compile information about each animal’s behavior. The team also wrote machine vision software to automatically extract information about each of the C. elegans motor programs — locomotion, feeding, egg-laying, and more — from these videos, yielding a near-comprehensive picture of each animal’s behavioral outputs. Flavell said the scope parts cost about $3,000 and can be assembled in a day or two using the team’s online tutorial. They have posted that and the system’s software online for free. The affordability and flexibility of these microscopes should allow them to be useful for many different applications in the biological sciences.

By using this system and then analyzing the data, Flavell’s team was able to identify for the first time a number of patterns of nematode behavior that involve the coordination of multiple motor actions. Flavell said one insight yielded by the system and the subsequent analysis is that the intensely studied nematodes, known scientifically as C. elegans, have more distinct behavioral states than generally assumed. For example, the study finds that the behavioral state known as “dwelling,” previously defined based on the animal staying put, actually consists of multiple different sub-states that could be readily identified using this new imaging approach.

Behaviors coordinated by dopamine

But one of the most pronounced new behavioral patterns that emerged from the analyses was the observation that worms lay many more eggs while roaming on a food lawn than they do while dwelling. This likely allows animals to thoroughly disperse their eggs across a nutritive environment. The two motor circuits that control locomotion and egg-laying in this animal had been carefully defined by previous work. So, based on their new observation, Flavell’s team decided to investigate how the worm’s nervous system couples locomotion and egg-laying together. It turned out to hinge on the neurotransmitter dopamine, which is abundant in all animals, including humans.

They started out by knocking out genes for various neurotransmitters and other brain-modulating molecules. Many of those candidates, such as serotonin, affected the animal’s behavior in important ways, but did not disrupt this coupling of roaming and egg laying. It was only when the team knocked out a gene called cat-2, which is needed for dopamine production, that the worms no longer increased their egg laying while roaming. Notably, it didn’t affect the pace of egg laying while dwelling, suggesting that the worms without dopamine were still capable of laying eggs normally while engaged in other behavioral states.

The team further confirmed the role of dopamine by taking direct control of dopamine-producing cells using optogenetics, a technology that allows neuron activity to be turned on or off with flashes of light. In these experiments, they learned that acutely shutting down the dopaminergic neurons reduced egg-laying only while animals were in the roaming state, but activating these neurons could drive the animals to start laying eggs, even under circumstances when the pace of egg-laying is normally low.

Next, the team wanted to know where the dopamine that triggers this coordinated response emerges, and when. They engineered worms so that their neurons would glow when they became electrically active, an indication provided by a surge of calcium ions. From those flashes they saw that a particular dopamine-producing neuron called PDE stood out as being especially active as worms roamed across a food lawn, and their activity fluctuated in association with the worms’ motion. It peaked, they saw, just before the worm assumed the posture that precipitates egg laying, but only when the worms were crawling along a bacterial food source. Notably, the neuron has the means — a little hair-like structure called a cilium — to sense food outside the worm’s body. These studies suggested that the PDE neuron integrates the presence of food in the environment with the worm’s own motion, generating an activity pattern that essentially reports how quickly worms are progressing through their nutritive environment. The release of dopamine by this neuron, and potentially others as well, could relay this information to the egg-laying circuit, allowing for coordination between the behaviors.

Flavell’s team also mapped out the neural circuitry downstream of dopamine and found that its effects are mediated by two receptors in the D2 family of dopamine receptors (dop-2 and dop-3). In addition, a set of neurons that utilize the neurotransmitter GABA appear to play a critical role downstream of dopamine release. They hypothesize that the role of dopamine may be to send the signal amid plentiful food and roaming behavior to override GABA’s inhibition of egg laying, allowing this behavior to proceed.

Ultimately, egg laying while roaming was just one example of motor program coupling that the lab chose to dissect. Flavell and co-authors note there are many others, too.

“One thing that excites us about this study is that it’s now easy with this new microscopy platform to simultaneously measure each of the main motor programs generated by this animal. Hopefully, we can start thinking about the full repertoire of behaviors that it generates as a complete, coordinated set,” the scientists say.

The research team notes that recently-developed technologies for whole-brain calcium imaging have opened the possibility of measuring neuronal activity throughout the brains of various animals, including the worm.

“To understand these comprehensive neural imaging datasets, it will be important to consider how they relate to the output of the whole brain: the full repertoire of behavioral outputs that an animal generates” Flavell says.

The paper’s other authors are Yung-Chi Huang and Saba Baskoylu. The National Science Foundation, the National Institutes of Health, the JPB Foundation, and the Brain and Behavior Research Foundation supported the research.

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Learning during lockdown

Despite the extraordinary pressures of adapting to the realities of the Covid-19 pandemic, learners have increasingly sought out MITx courses as a way to stay intellectually active, work toward longstanding goals, and affect change in themselves and in the world around them. MITx courses have seen over 500,000 enrollments since the start of the pandemic.

“It’s been humbling to witness the role our courses have played in learners’ lives these past few months,” says Dana Doyle, director of the MITx Program. “The number of people who are using their time at home to learn something new or make a change in their lives is inspiring.”

MITx instructors and staff have heard from learners from over a dozen countries across the globe, sharing their experiences during the pandemic. Some have used MITx courses to rediscover subjects they had once been passionate about; some are leveraging a career change; still others hope to pass on new knowledge to the next generation. The following represent just a few of their stories.

Between careers and countries

Paula Unger was just finishing up an internship in Peru when Covid-19 hit. “The first case was discovered in March, and the lockdown began eight days later,” she recalls. Unger, who recently received her degree in agricultural studies from the University of Bonn, had spent several months analyzing DNA sequencing data at the International Potato Center in Lima.

A Peruvian national, Unger had planned to return to her home in Aachen, Germany immediately following the internship to begin looking for jobs. Instead, she sheltered in place with her family in Lima, where lockdown was strictly enforced. “You could not even go outside for a walk, it’s totally prohibited,” she says. 

Unable to leave the house, Unger turned to a project she’d been putting off for some time: taking Professor Eric Lander’s Introduction to Biology MITx course. Though she earned her degree in a science-based field, Unger had spent a few years moving between majors and universities across Germany, and felt that a stronger background in biology would help her career. She didn’t count on how much she would enjoy the course for its own sake. 

“I’m mind-blown by how well the course is made,” she says, citing Lander’s engaging lectures and the course’s challenging, interactive problems sets as particularly valuable. “A lot of universities should learn to create courses that are as well-conceived pedagogically as these are.” Thanks to her MITx learning journey, Unger felt she was able to keep moving forward even while stuck in one place: “I could keep growing as a person, even though my life had been put on hold.”

Happily, Unger’s life and career were able to resume sooner than expected. Not long into lockdown, the Max Planck Institute for Plant Breeding Research in Cologne contacted her about a position, conducted an e-interview, and hired her with the promise that they would wait for her until she could return to Germany.

Now back in Aachen, Unger has started her new job, but has no plans to abandon her learning journey. She enrolled in the MITx Quantitative Biology Workshop, and plans eventually to return to school to complete a master’s degree. “I wish more people would realize the potential of what’s possible through online learning,” she says.

Between flights, Australian pilot learns to engineer spacecraft

When he’s not flying U.S. and Australian citizens back to their home countries as part of pandemic-related repatriation efforts, Sydney-based pilot Andrew Wangler necessarily has a lot of time on his hands.

While Wangler’s company maintains the “minimum viable international network” of flights, he’s been on and off furlough throughout the pandemic. When called up, he commutes 10 hours to Melbourne International Airport before flying to San Francisco or Los Angeles to drop off American nationals and pick up returning Australians.

Wangler joined Qantas after a 15-year career in the Royal Australian Air Force. He graduated from the Australian Defence Force Academy with a double major in mathematics and political science, and minors in physics and computer science, before completing an MBA; it’s safe to say that he loves to learn. So when he found himself stuck in a pattern of self-isolation at home and in hotels before and after each flight, Wangler was thrilled to find MITx courses that helped him rediscover yet another academic passion: spaceflight.

“Professor Hoffmann’s passion for the subject material and teaching style are very infectious and engaging,” says Wangler. Finding Hoffman’s Introduction to Aerospace Engineering course brought back fond memories of his interest in the subject as an undergraduate. These days, Wangler hopes to channel his own enthusiasm and what he’s learned from MITx to help his 12 year-old son, “hell-bent on being an engineer,” to find the right learning resources.

“As my son gets older, it will be helpful to have the engineering background, just to open his eyes and point him in the right direction,” says Wangler. Last year, father and son visited the Boeing facilities near Seattle as well as the Museum of Flight, including a session in the Space Shuttle Crew Trainer. They are planning more educational trips in the future, including Houston, Texas and Cape Canaveral, Florida.

In the meantime, Wangler’s enthusiasm for his online learning journey shows no signs of abating: while preparing for another flight to LAX, he emails, “I am actually enjoying Professor Hoffman’s archived course on Engineering the Space Shuttle as we speak!”

Under lockdown in Madrid, retiree rediscovers a love of physics 

Miguel Doñate has witnessed the effects of Covid-19 more directly than many. Under strict lockdown since March 15 in Madrid, Spain, Doñate is surrounded by reminders of the pandemic’s worst outcomes. 

“We have been in a very difficult situation here, with a lot of deaths, including people I know,” Doñate says. “Five hundred meters away from where I live, they created a morgue within a shopping mall.” Police keep tight control of the streets, regulating all forms of traffic. Doñate hasn't been able to leave the house except to buy necessities.

Doñate feels fortunate to have found intellectual stimulation and a welcome distraction in MITx courses on quantum mechanics, taught by Professor Barton Zwiebach. After retiring last year from a long career in information technology, Doñate, who earned his undergraduate degree in physics in 1978, turned to online courses as a way to reconnect with the field. After exploring a variety of options, he gravitated toward MITx courses for their rigor, engaging problem sets, and the support of the professor and an online community of learners.

When the pandemic began, all these qualities became even more important to him. “I’m very grateful to be able to do what I enjoy,” Doñate says. “These courses prevent me from turning on the TV to watch the news, or from looking at my phone, seeing people post negative things,” noting that deep political divisions have sprung up in his country.

Physics coursework has become an integral part of Doñate’s daily routine, helping him stay focused on the things that make him happy. He studies every weekday morning for three to four hours before moving on to chores and other household activities. This “productive isolation” allows him to stay positive, instead of dwelling on circumstances outside his control, including the future of his wife’s optics business, which has suffered as a result of the crisis. 

Still, unlike many in his situation, Doñate says he is determined to take life one day at a time: “I’m not just counting the days until this is over.” After 40 years away from the field, he’s fully occupied catching up on physics: “I’m very focused on the present; I have a lot of things to do.”

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Twelve MIT faculty honored as “Committed to Caring” for 2020-2021

The term “mentor” traces back to the ancient Greek author Homer. When Odysseus sets off for Troy, he entrusts his son Telemachus to a close friend, Mentor. Finding Telemachus floundering, the goddess Athena takes on the guise of Mentor, visiting and counseling Telemachus throughout “The Odyssey.” Athena, as Mentor, embodies this transfer of wisdom, compassion, and guidance; the term “mentor” has gone on to capture these sentiments.

Numerous professors at MIT echo this generosity of attention and care in their mentoring relationships with graduate students. The Committed to Caring (C2C) program recognizes outstanding mentors and promotes thoughtful, engaged mentorship throughout the Institute.

For considerate and humanizing acts such as validating students’ identities, inviting students to join in lab and departmental decision-making, and going to great lengths to ensure continuity in funding for students, 12 MIT faculty members were recently honored by their graduate students as stalwart mentors. These new honorees join 48 previous C2C honorees.

The following faculty members are the 2020-21 Committed to Caring Honorees:

• Daron Acemoglu, Department of Economics;
• Alfredo Alexander-Katz, Department of Materials Science and Engineering;
• Kristin Bergmann, Department of Earth, Atmospheric and Planetary Sciences;
• Kerri Cahoy, Department of Aeronautics and Astronautics;
• Catherine Drennan, departments of Biology and Chemistry;
• Colette Heald, Department of Civil and Environmental Engineering;
• Caroline Jones, Department of Architecture;
• Jesse Kroll, Department of Civil and Environmental Engineering;
• Gene-wei Li, Department of Biology;
• Anna Mikusheva, Department of Economics;
• Gigliola Staffilani, Department of Mathematics; and
• Lawrence Susskind, Department of Urban Studies and Planning.

Selecting for generous guidance

Every other year, the Office of Graduate Education invites graduate students to nominate professors for the Committed to Caring honor. A selection committee composed of graduate students and MIT staff members reads the nomination letters, settling on a pool of awardees who devote true attention to their students’ well-being. Selection criteria include the depth and breadth of faculty members’ caring actions, promoting the development of scholarly excellence in students, and the support of diversity, equity, and inclusion within the research groups and the wider community.

This year’s committee included Associate Dean for Graduate Education Suraiya Baluch (chair); Renée Caso (academic programs manager, Department of Architecture); and graduate students Courtney Lesoon (2017-19 C2C graduate community fellow; History, Theory, and Criticism section, Department of Architecture), Ellie Immerman (2019-20 C2C graduate community fellow, departments of History and Science, Technology, and Society), Noam Buckman (Department of Mechanical Engineering), Grace Putka Ahlqvist (Department of Chemistry), and Shayna Hilburg (Department of Materials Science and Engineering).

Baluch writes that she “was deeply moved to read about the many … acts of humanity and compassion that prioritized the well-being of graduate students. So many of the nomination letters spoke to the lasting impact these advisors had on their students’ professional and personal development.” The letters illustrated faculty advisors’ remarkable compassion and eagerness to wholeheartedly support their students.

In particular, these faculty tend to personalize their advising styles to the individual student; work collaboratively with students to navigate distressing life events; reassure students and help renew their love of the discipline when research results go awry; and empower students to guide their own research agendas. In the coming months, each of these honorees will be featured in an MIT News article and an accompanying poster campaign.

Faculty Peer Mentorship Program

During fall 2019, the Office of Graduate Education and Associate Provost Tim Jamison launched a pilot Faculty Peer Mentorship Program (FPMP). Ten of 29 entering untenured faculty members chose to participate. Each was matched with a previous Committed to Caring honoree.

The goal is for pairs to connect regularly throughout the year, discussing how to intentionally craft caring mentoring relationships with graduate students and postdocs. In building mentorship networks, the FPMP will help the Institute enact excellent mentorship as a community value.

Pilot faculty participants come from the schools of Science; Humanities, Arts and Social Sciences; Architecture and Planning; and Engineering. Blanche Staton, senior associate dean for graduate education, is “enthused by the wealth of advising wisdom and the eagerness of faculty members to help build a stronger MIT.”

Amid times of uncertainty and great stress, C2C honorees provide a foundation of support for the community, helping us to weather the strains and take care of each other, as well as ourselves.

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MIT Energy Initiative awards eight seed fund grants for early-stage MIT energy research

Eight individuals and teams from MIT were recently awarded $150,000 grants through the MIT Energy Initiative (MITEI) Seed Fund Program to support promising novel energy research. 

The highly competitive annual program received a total of 82 proposals from 88 researchers representing 17 departments, labs, and centers at MIT. The applications, which came from a range of disciplines, all aim to help advance a low-carbon energy system and address key climate challenges. 

“The breadth of creative, interdisciplinary research proposals that we received truly reflects the Institute’s increasing focus on curbing the effects of climate change,” says MITEI Director Robert C. Armstrong, the Chevron Professor of Chemical Engineering. He also noted that a large number of proposals focused on energy storage, signifying the central role that these technologies will play in deep decarbonization.

The winning projects will address topics ranging from hurricane-resilient smart grids and zero-emission neighborhoods to new, low-cost batteries for grid-level energy storage.

Building hurricane-resilient smart grids

In 2017, Hurricane Maria left more than 1 million Puerto Ricans without power — many of whom did not have their electricity restored until months later. As stronger hurricanes become increasingly frequent, extreme weather is proving to be a growing critical threat to electric power grids and energy infrastructure. 

First-time seed fund awardees Kerry Emanuel and Saurabh Amin aim to develop a foundational design approach for building hurricane-resilient smart grids. They will combine their expertise in hurricane physics and power system control to develop new strategies that can greatly increase the resilience of power grids and allow for quicker restoration of service.

“The goal is to reduce overall grid damage and avoid prolonged outages after storms by integrating strategic resource allocation and microgrid control strategies,” says Emanuel, the Cecil and Ida Green Professor in the Department of Earth, Atmospheric and Planetary Sciences. 

“Unlike a traditional centralized grid that depends on a reliable supply of bulk power, our design approach accounts for the uncertain failure rates of grid components due to hurricane winds and floods, and leverages the flexibility enabled by distributed energy resources, like reconfigurable microgrids, localized renewable energy, and storage devices,” adds Amin, an associate professor in the Department of Civil and Environmental Engineering and a member of the Laboratory for Information and Decision Systems.

This interdisciplinary research holds promise for advancing the science of climate risk management and helping government agencies and energy utilities work together to develop flexible operational strategies in preparation for future storms.

Biological self-assembly to improve catalysis

According to Ariel Furst, an assistant professor in the Department of Chemical Engineering, 500 gigatons of carbon dioxide (CO₂) are expected to be produced from industrial processing and fossil fuels over the next five decades. An important way to reduce the carbon footprint of one of these main emitters — industrial processing — is to transform CO₂ into useful products. 

The first step in this transformation process is to reduce CO₂ to carbon monoxide through a method such as electrocatalysis. This reaction — in which a small-molecule catalyst interacts with an electrode — can often be imprecise and limited. With this in mind, Furst plans to use her seed fund grant to explore how the specific placement of the small-molecule catalysts affects catalytic efficiency in CO₂ reduction.

“We provide a unique perspective to this work by combining the inherent power of biology with these electrocatalytic transformations,” says Furst, who is both a new MIT faculty member and first-time seed fund grant winner. 

She will use self-assembled nanostructures composed of deoxyribonucleic acids (DNA) to control the precise positioning of molecular catalysts on electrode surfaces. This research will allow her to evaluate spatial effects on catalytic efficiency, from which she can extrapolate design parameters that can be applied to other classes of catalysts in the future. 

Rapid material design for solid-state batteries

Another first-time seed fund award team will use their grant to develop an automated synthetic process to speed up the discovery, design, and construction of new ceramic material components for solid-state lithium-ion batteries (SSBs), which have the potential to increase safety and energy efficiency as compared to more conventional liquid-electrolyte batteries.

One of the major challenges with implementing SSBs is the need for a high ceramic manufacturing temperature to make key components, resulting in a high-cost, time-consuming synthesis that doesn’t easily translate into industrially relevant manufacturing. Looking to overcome this obstacle, the team has identified the potential for a low-temperature process to synthesize the ceramic components. 

The interdisciplinary team consists of a material ceramicist, Thomas Lord Associate Professor Jennifer Rupp of the departments of Materials Science and Engineering (DMSE) and Electrical Engineering and Computer Science (EECS); an automation expert, Professor Wojciech Matusik of EECS; and a material informatics expert, Atlantic Richfield Associate Professor of Energy Studies Elsa Olivetti of DMSE .

Leveraging their distinct expertise, the research team will work with students to couple machine learning techniques and automated synthesis to revise ceramic processing and enable rapid material screening, device design, and data analysis for performance engineering. 

“This work has the potential to fundamentally alter the way research is conducted in the battery community,” says Rupp. “The higher throughput pathway will allow more discoveries to be made in less time and will enable researchers to focus on altering battery design toward performance.”

The MITEI Seed Fund Program has supported 185 early-stage energy research projects through a total of $24.9 million in grants since its establishment in 2008. This funding comes primarily from MITEI’s founding and sustaining members, supplemented by gifts from generous donors.

Recipients of the 2020 MITEI Seed Fund grants are as follows:

• “Building Hurricane-Resilient Smart Grids: Optimal Resource Allocation and Microgrid Operation” — Kerry Emanuel of the Department of Earth, Atmospheric and Planetary Sciences and Saurabh Amin of the Department of Civil and Environmental Engineering;
• “DNA Nanostructure-Immobilized Electrocatalysts for Improved CO2 Reduction Efficiency” — Ariel Furst of the Department of Chemical Engineering;
• “Enabling High-Energy Li/Li-Ion Batteries Through Active Interface Repair” — Betar Gallant of the Department of Mechanical Engineering;
• “Extremely Low-Cost Aluminum-Sulfur Battery Running Below 100 Degrees Celsius for Grid-Level Energy Storage” — Donald Sadoway of the Department of Materials Science and Engineering;
• “Low-Cost Negative Emissions From Concentration Swing Absorption” — Jeffrey Grossman of the Department of Materials Science and Engineering;
• “Rapid Material Discovery for Solid-State Batteries: Coupling Low-Cost Processing With Material Screening and Performance Optimization Using Machine Learning” — Jennifer Rupp of the Department of Materials Science and Engineering, Wojciech Matusik of the Department of Electrical Engineering and Computer Science, and Elsa Olivetti of the Department of Materials Science and Engineering;
• “Sorption Enhanced Steam Methane Reforming With Molten Sorbents for Clean Hydrogen Production” — T. Alan Hatton of the Department of Chemical Engineering; and
• “Towards Zero-Emissions Neighborhoods: A Novel Building-Grid Optimization Framework” — Audun Botterud of the Laboratory for Information and Decision Systems and Christoph Reinhart of the Department of Architecture.

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The MIT Press and UC Berkeley launch Rapid Reviews: COVID-19

The MIT Press has announced the launch of Rapid Reviews: COVID-19 (RR:C19), an open access, rapid-review overlay journal that will accelerate peer review of Covid-19-related research and deliver real-time, verified scientific information that policymakers and health leaders can use.

Scientists and researchers are working overtime to understand the SARS-CoV-2 virus and are producing an unprecedented amount of preprint scholarship that is publicly available online but has not been vetted yet by peer review for accuracy. Traditional peer review can take four or more weeks to complete, but RR:C19’s editorial team, led by Editor-in-Chief Stefano M. Bertozzi, professor of health policy and management and dean emeritus of the School of Public Health at the University of California at Berkeley, will produce expert reviews in a matter of days.

Using artificial intelligence tools, a global team will identify promising scholarship in preprint repositories, commission expert peer reviews, and publish the results on an open access platform in a completely transparent process. The journal will strive for disciplinary and geographic breadth, sourcing manuscripts from all regions and across a wide variety of fields, including medicine; public health; the physical, biological, and chemical sciences; the social sciences; and the humanities. RR:C19 will also provide a new publishing option for revised papers that are positively reviewed.

Amy Brand, director of the MIT Press sees the no-cost open access model as a way to increase the impact of global research and disseminate high-quality scholarship. “Offering a peer-reviewed model on top of preprints will bring a level of diligence that clinicians, researchers, and others worldwide rely on to make sound judgments about the current crisis and its amelioration,” says Brand. “The project also aims to provide a proof-of-concept for new models of peer-review and rapid publishing for broader applications.”

Made possible by a $350,000 grant from the Patrick J. McGovern Foundation and hosted on PubPub, an open-source publishing platform from the Knowledge Futures Group for collaboratively editing and publishing journals, monographs, and other open access scholarly content, RR:C19 will limit the spread of misinformation about Covid-19, according to Bertozzi.

“There is an urgent need to validate — or debunk — the rapidly growing volume of Covid-19-related manuscripts on preprint servers,” explains Bertozzi. “I'm excited to be working with the MIT Press, the Patrick J. McGovern Foundation, and the Knowledge Futures Group to create a novel publishing model that has the potential to more efficiently translate important scientific results into action. We are also working with COVIDScholar, an initiative of UC Berkeley and Lawrence Berkeley National Lab, to create unique AI/machine learning tools to support the review of hundreds of preprints per week.”

“This project signals a breakthrough in academic publishing, bringing together urgency and scientific rigor so the world’s researchers can rapidly disseminate new discoveries that we can trust,” says Vilas Dhar, trustee of the Patrick J. McGovern Foundation. “We are confident the RR:C19 journal will quickly become an invaluable resource for researchers, public health officials, and healthcare providers on the frontline of this pandemic. We’re also excited about the potential for a long-term transformation in how we evaluate and share research across all scientific disciplines.”

On the collaboration around this new journal, Travis Rich, executive director of the Knowledge Futures Group notes, “At a moment when credibility is increasingly crucial to the well-being of society, we’re thrilled to be partnering with this innovative journal to expand the idea of reviews as first-class research objects, both on PubPub and as a model for others.

RR:C19 will publish its first reviews in July 2020 and is actively recruiting potential reviewers and contributors. To learn more about this project and its esteemed editorial board, visit rapidreviewscovid19.mitpress.mit.edu.

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Engineers use “DNA origami” to identify vaccine design rules

By folding DNA into a virus-like structure, MIT researchers have designed HIV-like particles that provoke a strong immune response from human immune cells grown in a lab dish. Such particles might eventually be used as an HIV vaccine.

The DNA particles, which closely mimic the size and shape of viruses, are coated with HIV proteins, or antigens, arranged in precise patterns designed to provoke a strong immune response. The researchers are now working on adapting this approach to develop a potential vaccine for SARS-CoV-2, and they anticipate it could work for a wide variety of viral diseases.

“The rough design rules that are starting to come out of this work should be generically applicable across disease antigens and diseases,” says Darrell Irvine, who is the Underwood-Prescott Professor with appointments in the departments of Biological Engineering and Materials Science and Engineering; an associate director of MIT’s Koch Institute for Integrative Cancer Research; and a member of the Ragon Institute of MGH, MIT, and Harvard.

Irvine and Mark Bathe, an MIT professor of biological engineering and an associate member of the Broad Institute of MIT and Harvard, are the senior authors of the study, which appears today in Nature Nanotechnology. The paper’s lead authors are former MIT postdocs Rémi Veneziano and Tyson Moyer.

DNA design

Because DNA molecules are highly programmable, scientists have been working since the 1980s on methods to design DNA molecules that could be used for drug delivery and many other applications, most recently using a technique called DNA origami that was invented in 2006 by Paul Rothemund of Caltech.

In 2016, Bathe’s lab developed an algorithm that can automatically design and build arbitrary three-dimensional virus-like shapes using DNA origami. This method offers precise control over the structure of synthetic DNA, allowing researchers to attach a variety of molecules, such as viral antigens, at specific locations.

“The DNA structure is like a pegboard where the antigens can be attached at any position,” Bathe says. “These virus-like particles have now enabled us to reveal fundamental molecular principles of immune cell recognition for the first time.”

Natural viruses are nanoparticles with antigens arrayed on the particle surface, and it is thought that the immune system (especially B cells) has evolved to efficiently recognize such particulate antigens. Vaccines are now being developed to mimic natural viral structures, and such nanoparticle vaccines are believed to be very effective at producing a B cell immune response because they are the right size to be carried to the lymphatic vessels, which send them directly to B cells waiting in the lymph nodes. The particles are also the right size to interact with B cells and can present a dense array of viral particles.

However, determining the right particle size, spacing between antigens, and number of antigens per particle to optimally stimulate B cells (which bind to target antigens through their B cell receptors) has been a challenge. Bathe and Irvine set out to use these DNA scaffolds to mimic such viral and vaccine particle structures, in hopes of discovering the best particle designs for B cell activation.

“There is a lot of interest in the use of virus-like particle structures, where you take a vaccine antigen and array it on the surface of a particle, to drive optimal B-cell responses,” Irvine says. “However, the rules for how to design that display are really not well-understood.”

Other researchers have tried to create subunit vaccines using other kinds of synthetic particles, such as polymers, liposomes, or self-assembling proteins, but with those materials, it is not possible to control the placement of viral proteins as precisely as with DNA origami.

For this study, the researchers designed icosahedral particles with a similar size and shape as a typical virus. They attached an engineered HIV antigen related to the gp120 protein to the scaffold at a variety of distances and densities. To their surprise, they found that the vaccines that produced the strongest response B cell responses were not necessarily those that packed the antigens as closely as possible on the scaffold surface.

“It is often assumed that the higher the antigen density, the better, with the idea that bringing B cell receptors as close together as possible is what drives signaling. However, the experimental result, which was very clear, was that actually the closest possible spacing we could make was not the best. And, and as you widen the distance between two antigens, signaling increased,” Irvine says.

The findings from this study have the potential to guide HIV vaccine development, as the HIV antigen used in these studies is currently being tested in a clinical trial in humans, using a protein nanoparticle scaffold.

Based on their data, the MIT researchers worked with Jayajit Das, a professor of immunology and microbiology at Ohio State University, to develop a model to explain why greater distances between antigens produce better results. When antigens bind to receptors on the surface of B cells, the activated receptors crosslink with each other inside the cell, enhancing their response. However, the model suggests that if the antigens are too close together, this response is diminished.

Beyond HIV

In recent months, Bathe’s lab has created a variant of this vaccine with the Aaron Schmidt and Daniel Lingwood labs at the Ragon Institute, in which they swapped out the HIV antigens for a protein found on the surface of the SARS-CoV-2 virus. They are now testing whether this vaccine will produce an effective response against the coronavirus SARS-CoV-2 in isolated B cells, and in mice.

“Our platform technology allows you to easily swap out different subunit antigens and peptides from different types of viruses to test whether they may potentially be functional as vaccines,” Bathe says.

Because this approach allows for antigens from different viruses to be carried on the same DNA scaffold, it could be possible to design variants that target multiple types of coronaviruses, including past and potentially future variants that may emerge, the researchers say.

Bathe was recently awarded a grant from the Fast Grants Covid-19 fund to develop their SARS-CoV-2 vaccine. The HIV research presented in the Nature Nanotechnology paper was funded by the Human Frontier Science Program, the U.S. Office of Naval Research, the U.S. Army Research Office through MIT’s Institute for Soldier Nanotechnologies, the Ragon Institute, and the U.S. National Institutes of Health.

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Producing a gaseous messenger molecule inside the body, on demand

Nitric oxide is an important signaling molecule in the body, with a role in building nervous system connections that contribute to learning and memory. It also functions as a messenger in the cardiovascular and immune systems.

But it has been difficult for researchers to study exactly what its role is in these systems and how it functions. Because it is a gas, there has been no practical way to direct it to specific individual cells in order to observe its effects. Now, a team of scientists and engineers at MIT and elsewhere has found a way of generating the gas at precisely targeted locations inside the body, potentially opening new lines of research on this essential molecule’s effects.

The findings are reported today in the journal Nature Nanotechnology, in a paper by MIT professors Polina Anikeeva, Karthish Manthiram, and Yoel Fink; graduate student Jimin Park; postdoc Kyoungsuk Jin; and 10 others at MIT and in Taiwan, Japan, and Israel.

“It’s a very important compound,” Anikeeva says. But figuring out the relationships between the delivery of nitric oxide to particular cells and synapses, and the resulting higher-level effects on the learning process has been difficult. So far, most studies have resorted to looking at systemic effects, by knocking out genes responsible for the production of enzymes the body uses to produce nitric oxide where it’s needed as a messenger.

But that approach, she says, is “very brute force. This is a hammer to the system because you’re knocking it out not just from one specific region, let’s say in the brain, but you essentially knock it out from the entire organism, and this can have other side effects.”

Others have tried introducing compounds into the body that release nitric oxide as they decompose, which can produce somewhat more localized effects, but these still spread out, and it is a very slow and uncontrolled process.

The team’s solution uses an electric voltage to drive the reaction that produces nitric oxide. This is similar to what is happening on a much larger scale with some industrial electrochemical production processes, which are relatively modular and controllable, enabling local and on-demand chemical synthesis. “We've taken that concept and said, you know what? You can be so local and so modular with an electrochemical process that you can even do this at the level of the cell,” Manthiram says. “And I think what’s even more exciting about this is that if you use electric potential, you have the ability to start production and stop production in a heartbeat.”

The team’s key achievement was finding a way for this kind of electrochemically controlled reaction to be operated efficiently and selectively at the nanoscale. That required finding a suitable catalyst material that could generate nitric oxide from a benign precursor material. They found that nitrite offered a promising precursor for electrochemical nitric oxide generation.

“We came up with the idea of making a tailored nanoparticle to catalyze the reaction,” Jin says. They found that the enzymes that catalyze nitric oxide generation in nature contain iron-sulfur centers. Drawing inspiration from these enzymes, they devised a catalyst that consisted of nanoparticles of iron sulfide, which activates the nitric oxide-producing reaction in the presence of an electric field and nitrite. By further doping these nanoparticles with platinum, the team was able to enhance their electrocatalytic efficiency.

To miniaturize the electrocatalytic cell to the scale of biological cells, the team has created custom fibers containing the positive and negative microelectrodes, which are coated with the iron sulfide nanoparticles, and a microfluidic channel for the delivery of sodium nitrite, the precursor material. When implanted in the brain, these fibers direct the precursor to the specific neurons. Then the reaction can be activated at will electrochemically, through the electrodes in the same fiber, producing an instant burst of nitric oxide right at that spot so that its effects can be recorded in real-time.

As a test, they used the system in a rodent model to activate a brain region that is known to be a reward center for motivation and social interaction, and that plays a role in addiction. They showed that it did indeed provoke the expected signaling responses, demonstrating its effectiveness.

Anikeeva says this “would be a very useful biological research platform, because finally, people will have a way to study the role of nitric oxide at the level of single cells, in whole organisms that are performing tasks.” She points out that there are certain disorders that are associated with disruptions of the nitric oxide signaling pathway, so more detailed studies of how this pathway operates could help lead to treatments.

The method could be generalizable, Park says, as a way of producing other molecules of biological interest within an organism. “Essentially we can now have this really scalable and miniaturized way to generate many molecules, as long as we find the appropriate catalyst, and as long as we find an appropriate starting compound that is also safe.” This approach to generating signaling molecules in situ could have wide applications in biomedicine, he says.

“One of our reviewers for this manuscript pointed out that this has never been done — electrolysis in a biological system has never been leveraged to control biological function,” Anikeeva says. “So, this is essentially the beginning of a field that could potentially be very useful” to study molecules that can be delivered at precise locations and times, for studies in neurobiology or any other biological functions. That ability to make molecules on demand inside the body could be useful in fields such as immunology or cancer research, she says.

The project got started as a result of a chance conversation between Park and Jin, who were friends working in different fields — neurobiology and electrochemistry. Their initial casual discussions ended up leading to a full-blown collaboration between several departments. But in today’s locked-down world, Jin says, such chance encounters and conversations have become less likely. “In the context of how much the world has changed, if this were in this era in which we’re all apart from each other, and not in 2018, there is some chance that this collaboration may just not ever have happened.”

“This work is a milestone in bioelectronics,” says Bozhi Tian, an associate professor of chemistry at the University of Chicago, who was not connected to this work. “It integrates nanoenabled catalysis, microfluidics, and traditional bioelectronics … and it solves a longstanding challenge of precise neuromodulation in the brain, by in situ generation of signaling molecules. This approach can be widely adopted by the neuroscience community and can be generalized to other signaling systems, too.”

Besides MIT, the team included researchers at National Chiao Tung University in Taiwan, NEC Corporation in Japan, and the Weizman Institute of Science in Israel. The work was supported by the National Institute for Neurological Disorders and Stroke, the National Institutes of Health, the National Science Foundation, and MIT’s Department of Chemical Engineering.

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CSAIL robot disinfects Greater Boston Food Bank

With every droplet that we can’t see, touch, or feel dispersed into the air, the threat of spreading Covid-19 persists. It’s become increasingly critical to keep these heavy droplets from lingering — especially on surfaces, which are welcoming and generous hosts. 

Thankfully, our chemical cleaning products are effective, but using them to disinfect larger settings can be expensive, dangerous, and time-consuming. Across the globe there are thousands of warehouses, grocery stores, schools, and other spaces where cleaning workers are at risk.

With that in mind, a team from MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL), in collaboration with Ava Robotics and the Greater Boston Food Bank (GBFB), designed a new robotic system that powerfully disinfects surfaces and neutralizes aerosolized forms of the coronavirus.

The approach uses a custom UV-C light fixture designed at CSAIL that is integrated with Ava Robotics’ mobile robot base. The results were encouraging enough that researchers say that the approach could be useful for autonomous UV disinfection in other environments, such as factories, restaurants, and supermarkets. 

UV-C light has proven to be effective at killing viruses and bacteria on surfaces and aerosols, but it’s unsafe for humans to be exposed. Fortunately, Ava’s telepresence robot doesn’t require any human supervision. Instead of the telepresence top, the team subbed in a UV-C array for disinfecting surfaces. Specifically, the array uses short-wavelength ultraviolet light to kill microorganisms and disrupt their DNA in a process called ultraviolet germicidal irradiation.

The complete robot system is capable of mapping the space — in this case, GBFB’s warehouse — and navigating between waypoints and other specified areas. In testing the system, the team used a UV-C dosimeter, which confirmed that the robot was delivering the expected dosage of UV-C light predicted by the model.

“Food banks provide an essential service to our communities, so it is critical to help keep these operations running,” says Alyssa Pierson, CSAIL research scientist and technical lead of the UV-C lamp assembly. “Here, there was a unique opportunity to provide additional disinfecting power to their current workflow, and help reduce the risks of Covid-19 exposure.” 

Food banks are also facing a particular demand due to the stress of Covid-19. The United Nations projected that, because of the virus, the number of people facing severe food insecurity worldwide could double to 265 million. In the United States alone, the five-week total of job losses has risen to 26 million, potentially pushing millions more into food insecurity. 

During tests at GBFB, the robot was able to drive by the pallets and storage aisles at a speed of roughly 0.22 miles per hour. At this speed, the robot could cover a 4,000-square-foot space in GBFB’s warehouse in just half an hour. The UV-C dosage delivered during this time can neutralize approximately 90 percent of coronaviruses on surfaces. For many surfaces, this dose will be higher, resulting in more of the virus neutralized.

Typically, this method of ultraviolet germicidal irradiation is used largely in hospitals and medical settings, to sterilize patient rooms and stop the spread of microorganisms like methicillin-resistant staphylococcus aureus and Clostridium difficile, and the UV-C light also works against airborne pathogens. While it’s most effective in the direct “line of sight,” it can get to nooks and crannies as the light bounces off surfaces and onto other surfaces. 

"Our 10-year-old warehouse is a relatively new food distribution facility with AIB-certified, state-of-the-art cleanliness and food safety standards,” says Catherine D’Amato, president and CEO of the Greater Boston Food Bank. “Covid-19 is a new pathogen that GBFB, and the rest of the world, was not designed to handle. We are pleased to have this opportunity to work with MIT CSAIL and Ava Robotics to innovate and advance our sanitation techniques to defeat this menace." 

As a first step, the team teleoperated the robot to teach it the path around the warehouse — meaning it’s equipped with autonomy to move around, without the team needing to navigate it remotely. 

It can go to defined waypoints on its map, such as going to the loading dock, then the warehouse shipping floor, then returning to base. They define those waypoints from the expert human user in teleop mode, and then can add new waypoints to the map as needed. 

Within GBFB, the team identified the warehouse shipping floor as a “high-importance area” for the robot to disinfect. Each day, workers stage aisles of products and arrange them for up to 50 pickups by partners and distribution trucks the next day. By focusing on the shipping area, it prioritizes disinfecting items leaving the warehouse to reduce Covid-19 spread out into the community.

Currently, the team is exploring how to use its onboard sensors to adapt to changes in the environment, such that in new territory, the robot would adjust its speed to ensure the recommended dosage is applied to new objects and surfaces. 

A unique challenge is that the shipping area is constantly changing, so each night, the robot encounters a slightly new environment. When the robot is deployed, it doesn’t necessarily know which of the staging aisles will be occupied, or how full each aisle might be. Therefore, the team notes that they need to teach the robot to differentiate between the occupied and unoccupied aisles, so it can change its planned path accordingly.

As far as production went, “in-house manufacturing” took on a whole new meaning for this prototype and the team. The UV-C lamps were assembled in Pierson's basement, and CSAIL PhD student Jonathan Romanishin crafted a makeshift shop in his apartment for the electronics board assembly. 

“As we drive the robot around the food bank, we are also researching new control policies that will allow the robot to adapt to changes in the environment and ensure all areas receive the proper estimated dosage,” says Pierson. “We are focused on remote operation to minimize  human supervision, and, therefore, the additional risk of spreading Covid-19, while running our system.” 

For immediate next steps, the team is focused on increasing the capabilities of the robot at GBFB, as well as eventually implementing design upgrades. Their broader intention focuses on how to make these systems more capable at adapting to our world: how a robot can dynamically change its plan based on estimated UV-C dosages, how it can work in new environments, and how to coordinate teams of UV-C robots to work together.

“We are excited to see the UV-C disinfecting robot support our community in this time of need,” says CSAIL director and project lead Daniela Rus. “The insights we received from the work at GBFB has highlighted several algorithmic challenges. We plan to tackle these in order to extend the scope of autonomous UV disinfection in complex spaces, including dorms, schools, airplanes, and grocery stores.” 

Currently, the team’s focus is on GBFB, although the algorithms and systems they are developing could be transferred to other use cases in the future, like warehouses, grocery stores, and schools. 

"MIT has been a great partner, and when they came to us, the team was eager to start the integration, which took just four weeks to get up and running,” says Ava Robotics CEO Youssef Saleh. “The opportunity for robots to solve workplace challenges is bigger than ever, and collaborating with MIT to make an impact at the food bank has been a great experience." 

Pierson and Romanishin worked alongside Hunter Hansen (software capabilities), Bryan Teague of MIT Lincoln Laboratory (who assisted with the UV-C lamp assembly), Igor Gilitschenski and Xiao Li (assisting with future autonomy research), MIT professors Daniela Rus and Saman Amarasinghe, and Ava leads Marcio Macedo and Youssef Saleh. 

This project was supported in part by Ava Robotics, who provided their platform and team support.

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Biology community holds daylong program to address diversity and inclusion

On June 10, as part of the #ShutDownSTEM, #ShutDownAcademia, and #Strike4BlackLives national initiative, members of the Department of Biology took the day to engage in open conversations about racial bias, diversity, and inclusion.

The #ShutDownSTEM.MITbio program, organized by trainees, postdocs, and staff, included 13 virtual sessions on topics ranging from allyship and white privilege to anti-Blackness in Boston and the history of racism in science. The goal was to provide a space for white and non-Black people of color (POC) to educate themselves and offer support to Black colleagues, as well as determine ways to make the biology community more equitable.

In a letter to the department publicizing the June 10 event, the organizers wrote: “We have a responsibility as scientists to educate ourselves and initiate and continue difficult but necessary conversations on race and how systemic racism impacts ourselves and our field, particularly through the lens of recent events and how we can better support, amplify, and listen to our Black community members within the department and within our larger communities.”

Although the event came together in just a few days, more than 45 community members volunteered to help facilitate — and over 200 participated in concurrent sessions at any given time throughout the day.

Graduate student Talya Levitz heard about the #ShutDownSTEM initiative through various student activism channels a week prior. She brought the idea to department affinity groups, including the Biology Diversity Community (BDC), and ultimately aggregated over nine co-organizers. Other departments, labs, and centers across MIT developed their own initiatives, and Levitz’s team worked closely with their counterparts in the Department of Chemistry to share resources.

When they built the day’s agenda, Levitz says they had two main goals. “First, we wanted people to think about how their own identities intersect with anti-Blackness and anti-racism efforts,” she says. “The other big goal was to meet people where they are, and recognize that everyone is at a different place on their personal growth trajectories.”

Meghann Kasal, graduate student and co-founder of the BDC, responded to Levitz’s call to action immediately. “The #ShutDownSTEM program seemed like a great way to continue conversations that the BDC was already having, and transform dialogue into action,” she says. “It was a chance to empower people to make changes on an individual level and have those personal commitments ripple out to the larger community.”

SaRa Kim, administrative assistant and research technician, joined Levitz, Kasal, and others to help encourage other staff members to get involved. “The onus to make changes shouldn’t fall solely on those experiencing injustices,” she says, “and many of the co-organizers already had an active network of peers ready to provide support.”

Before the event, the team sent out a list of relevant resources, and afterward they collated a docket of action items to ensure that the conversation would continue — especially regarding recruiting and retaining Black and non-Black POC graduate students, staff, and faculty. Plans are also coalescing to apply for a Quality of Life grant to sponsor similar programs in the future, and students have spearheaded a faculty-matched donation drive within the department.

Graduate student and co-organizer Gerardo Perez Goncalves aims to take the day’s discussions and turn them into tangible plans with concrete timelines. “We need to hold each other accountable, and make sure those goals don’t get lost in committees,” he says. “Even though I’m just one person, I can be involved in a number of different ways, such as helping to craft actionable plans to spread awareness of current initiatives to those near me. The whole department needs to be made aware of these initiatives and plans so that we can establish community accountability.”

Sora Kim, a fellow graduate student and co-organizer, adds that scientists are often expected to separate their personal lives from their work. “You’re not supposed to bring what you personally think into the workplace,” Kim says, “but we know from history and current events that these things bleed into one another, and not talking about them creates a culture of silence and isolation.”

In the past, students have voiced concerns via anonymous polls and surveys, but there have been few opportunities for the entire community to come together, acknowledge current issues, and brainstorm solutions collaboratively.

The #ShutDownSTEM.MITbio event marked the beginning of what the organizing committee hopes will become substantive action to combat racism and build a more diverse, inclusive, and equitable community within both the department and the Institute. Already, open letters and petitions are circulating asking for concrete actions from leadership. 

“#ShutDownSTEM was not the start of these conversations for many people, but a continuation of ongoing discussions,” Kasal says. “We’ve wanted to hold these kinds of events before, but didn’t have the bandwidth in the BDC. This has given me hope that people will come together and help, and that it’s possible to organize something like this with just a few days of planning.”

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Ali Jadbabaie named head of the Department of Civil and Environmental Engineering

Ali Jadbabaie, the JR East Professor of Engineering, has been named the new head of the Department of Civil and Environmental Engineering (CEE), effective Sept. 1.

“Ali’s work has crossed disciplines and departments and led to multi-university collaborations,” says Anantha Chandrakasan, dean of the MIT School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science, in an announcement to the CEE community. “He has made outstanding contributions as an educator, in addition to serving as a leader in MIT’s multi-disciplinary efforts — particularly in understanding the dynamics of social networks, spreading processes, collective behavior, and collective decision-making in socio-technical systems. He will undoubtedly be a remarkable next leader for CEE.”

Jadbabaie succeeds Markus Buehler, the McAfee Professor of Engineering, who has led CEE since 2013. “I am grateful to Markus for his leadership, dedication, and contributions to helping shape CEE across the past seven years,” says Chandrakasan.

Currently, Jadbabaie also serves as associate director of the Institute for Data, Systems, and Society (IDSS), director of the Sociotechnical Systems Research Center, and a principal investigator in the Laboratory for Information and Decision Systems (LIDS). He has made fundamental contributions in optimization-based control, multi-agent coordination and consensus, collective decision-making, network science, and network economics. 

Jadbabaie graduated from Sharif University of Technology with a BS in electrical engineering (with a focus on control systems), and went on to receive his MS in electrical and computer engineering from the University of New Mexico, and his PhD in control and dynamical systems from Caltech. His work as a postdoc at Yale University set him on career path in network science and multi-agent coordination and control.

Jadbabaie spent 14 years at the University of Pennsylvania, where he held the Alfred Fitler Moore Professorship of Network Sciences in the Department of Electrical and Systems Engineering. He also held secondary appointments in the Department of Computer and Information Science as well as the Department of Operations, Information and Decisions in the Wharton School. In 2014, Ali was recruited to join MIT as a visiting professor, to help lay the groundwork for the new IDSS, which included the establishment of its flagship doctoral program in Social and Engineering Systems (SES). He also served as interim director of the Sociotechnical Systems Research Center. In 2016, he formally joined the MIT faculty with a joint appointment in the Department of Civil and Environmental Engineering and the IDSS.

In recognition of his work on multi-agent coordination and control and network science, Ali was named an IEEE Fellow; he also served as the inaugural editor-in-chief of IEEE Transactions on Network Science and Engineering, an interdisciplinary journal sponsored by several IEEE societies. He is a 2016 recipient of a Vannevar Bush Fellowship from the Office of the Secretary of Defense, in addition to being the recipient of a National Science Foundation Career Award, an Office of Naval Research Young Investigator Award, the O. Hugo Schuck Best Paper Award from the American Automatic Control Council, and the George S. Axelby Best Paper Award from the IEEE Control Systems Society. Several of his student advisees have also won best paper awards.

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How cancer drugs find their targets

In the watery inside of a cell, complex processes take place in tiny functional compartments called organelles. Energy-producing mitochondria are organelles, as is the frilly golgi apparatus, which helps to transport cellular materials. Both of these compartments are bound by thin membranes.

But in the past few years, research at Whitehead Institute and elsewhere has shown that there are other cellular organelles held together without a membrane. These organelles, called condensates, are tiny droplets which keep certain proteins close together amidst the chaos of the cell, allowing complex functions to take place within. “We know of about 20 types of condensate in the cell so far,” says Isaac Klein, a postdoc in Richard Young’s lab at the Whitehead Institute and oncologist at the Dana-Farber Cancer Institute.

Now, in a paper published in Science on June 19, Klein and Ann Boija, another postdoc in Young’s lab, show the mechanism by which small molecules, including cancer drugs, are concentrated in these cellular droplets — a finding that could have implications for the development of new cancer therapeutics. If researchers could tailor a chemical to seek out and concentrate in one kind of droplet in particular, it might have a positive effect on the delivery efficiency of the drug. “We thought, maybe that's an avenue by which we can improve cancer treatments and discover new ones,” says Klein.

“This [research] is part of a revolutionary new way of looking at the organization within cells,” says MIT Institute Professor Phillip Sharp, a professor of biology at the Koch Institute for Integrative Cancer Research and a co-author on the study. “Cells are not little pools of soup, all mixed together. They are actually highly organized, compartmentalized units, and that organization is important in their function and in their diseases. We've just started to understand that, and this new paper is a really important step, using that insight, to understand how to potentially treat diseases differently.”

Condensates and drug delivery

To explore how different properties of condensates inside the cell’s nucleus affected the delivery of cancer drugs, Boija and Klein selected a few example condensates to study. These included splicing speckles, which store cellular materials needed for RNA splicing; nucleoli, where ribosomes are formed; and a new kind of droplet Young’s lab discovered in 2018 called a transcriptional condensate. These new condensates bring together all the different proteins needed to successfully transcribe a gene. 

The researchers created their own suite of four different fluorescently-labeled condensates by adding glowing tags to marker proteins specific to each kind of droplet. For example, transcriptional condensates are marked by the droplet-forming protein MED1, splicing speckles by a protein called SRSF2, and nucleoli by FIB1 and NPM1. 

Now that they could tell individual droplets apart by their cellular purpose, the team, along with the help of Nathanael Gray, a chemical biologist at Harvard University and the Dana-Farber Cancer Institute, created fluorescent versions of clinically important drugs. The tested drugs included cisplatin and mitoxantrone, two anti-tumor medicines commonly used in chemotherapy. These therapeutics were the perfect test subjects, because they both target proteins that lie within nuclear condensates. 

The researchers added the cancer drugs to a mixture containing various droplets (and only droplets, none of the actual drug targets), and found that the drugs sorted themselves into specific condensates. Mitoxantrone concentrated in condensates marked by MED1, FIB1 and NPM1, selectively avoiding the others. Cisplatin, too, showed a particular affinity for droplets held together by MED1. 

“The big discovery with these in vitro studies is that a drug can concentrate within transcriptional condensate independent of its target,” Boija says. “We used to think that drugs come to the right place because their targets are there, but in our in vitro system, the target is not there. That’s really informative — it shows the drug is actually being concentrated in a different way than we thought.”    

To understand why some drugs were drawn into transcriptional condensates, they screened a panel of chemically-modified dyes and found that the important part of many drugs — the part that led them to concentrate in transcriptional condensates — is the molecules’ aromatic ring structure. Aromatic rings are stable, ring-shaped groupings of carbon atoms. The aromatic ring in some drugs are thought to stack with rings in MED1’s amino acids, leading the drug to concentrate in transcriptional condensates. 

Being able to tailor a drug to enter a certain condensate is a powerful tool for drug developers. “We found that if we add an aromatic group to a molecule, it becomes concentrated within the transcriptional condensate,” Boija says. “It's that type of interaction that is important when we design new drugs to enter transcriptional condensates — and maybe we can improve existing drugs by modifying their structure. This will be very exciting to look into.”

Where drugs concentrate affects how well they fight cancer

In order for this tool to be practically useful in drug development, the researchers had to make sure that concentration in specific droplets would actually impact the drugs’ performance. Boija and Klein decided to test this using cisplatin, which is drawn to transcriptional condensates by MED1 and works to fight cancer by adding clunky platinum molecules to DNA strands. This damages tumor cells’ genetic material. When the researchers administered cisplatin to a mixture of different condensates, both in the test tube and in cells, the drug preferentially altered DNA that lay within transcriptional condensates. 

This could explain why cisplatin and other platinum drugs are effective against so many diverse cancers, says Young, who is also a professor of biology at MIT; cancer-causing genes often carry regions of DNA called super enhancers, which are extremely active in transcription, leading to very large transcriptional condensates. “We now think the reason that drugs like cisplatin can work well in patients with diverse cancers is because they're becoming selectively concentrated at the cancer-causing genes, where these large transcriptional condensates occur,” he says. “The effect is to have the drug home in on the gene that's causing each cancer to be so deadly.”

A drug resistance mystery, solved        

The new insights in condensate behavior also provided some answers to another question in cancer research: why people become immune to the breast cancer drug tamoxifen.Tamoxifen works by attaching itself to estrogen receptors in the cancer cells, preventing them from getting the hormones they need to grow and eventually slowing or stopping the formation of new cancer cells altogether. The drug is one of the most effective treatments for the disease, reducing recurrence rates for ER+ breast cancers by around 50 percent.     

Unfortunately, many patients quickly develop a resistance to tamoxifen — sometimes as soon as a few months after they start taking it. This happens in a variety of ways — for example, sometimes the cancer cells will mutate to be able to kick the tamoxifen out of the cells, or simply produce fewer estrogen receptors for the drug to bind. One form of resistance was associated with an overproduction of the protein MED1, but scientists didn’t know why. 

With their newfound knowledge of how a drug’s activity is affected by where it concentrates, Boija and Klein had a hypothesis: The extra MED1 might increase the size of the droplets, effectively diluting the concentration of tamoxifen and making it more difficult for the drug to bind its targets. When they tested this in the laboratory, the team found that more MED1 did indeed cause larger droplets, leading to lower concentrations of tamoxifen. 

A new toolset for drug designers

The ability to better understand the behavior of drugs in cancer cells — how they concentrate, and why the cancer could become resistant to them — may provide drug developers with a new arsenal of tools to craft efficient therapeutics.

“This study suggests that we should be exploring whether we can design or isolate drugs that are concentrated in a given condensate, and to understand how existing drugs are concentrated in the cell,” says Phil Sharp. “I think this is really important for drug development — and I think [figuring it out] is going to be fun.”

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A focused approach to imaging neural activity in the brain

When neurons fire an electrical impulse, they also experience a surge of calcium ions. By measuring those surges, researchers can indirectly monitor neuron activity, helping them to study the role of individual neurons in many different brain functions.

One drawback to this technique is the crosstalk generated by the axons and dendrites that extend from neighboring neurons, which makes it harder to get a distinctive signal from the neuron being studied. MIT engineers have now developed a way to overcome that issue, by creating calcium indicators, or sensors, that accumulate only in the body of a neuron.

“People are using calcium indicators for monitoring neural activity in many parts of the brain,” says Edward Boyden, the Y. Eva Tan Professor in Neurotechnology and a professor of biological engineering and of brain and cognitive sciences at MIT. “Now they can get better results, obtaining more accurate neural recordings that are less contaminated by crosstalk.”

To achieve this, the researchers fused a commonly used calcium indicator called GCaMP to a short peptide that targets it to the cell body. The new molecule, which the researchers call SomaGCaMP, can be easily incorporated into existing workflows for calcium imaging, the researchers say.

Boyden is the senior author of the study, which appears today in Neuron. The paper’s lead authors are Research Scientist Or Shemesh, postdoc Changyang Linghu, and former postdoc Kiryl Piatkevich.

Molecular focus

The GCaMP calcium indicator consists of a fluorescent protein attached to a calcium-binding protein called calmodulin, and a calmodulin-binding protein called M13 peptide. GCaMP fluoresces when it binds to calcium ions in the brain, allowing researchers to indirectly measure neuron activity.

“Calcium is easy to image, because it goes from a very low concentration inside the cell to a very high concentration when a neuron is active,” says Boyden, who is also a member of MIT’s McGovern Institute for Brain Research, Media Lab, and Koch Institute for Integrative Cancer Research.

The simplest way to detect these fluorescent signals is with a type of imaging called one-photon microscopy. This is a relatively inexpensive technique that can image large brain samples at high speed, but the downside is that it picks up crosstalk between neighboring neurons. GCaMP goes into all parts of a neuron, so signals from the axons of one neuron can appear as if they are coming from the cell body of a neighbor, making the signal less accurate.

A more expensive technique called two-photon microscopy can partly overcome this by focusing light very narrowly onto individual neurons, but this approach requires specialized equipment and is also slower.

Boyden’s lab decided to take a different approach, by modifying the indicator itself, rather than the imaging equipment.

“We thought, rather than optically focusing light, what if we molecularly focused the indicator?” he says. “A lot of people use hardware, such as two-photon microscopes, to clean up the imaging. We’re trying to build a molecular version of what other people do with hardware.”

In a related paper that was published last year, Boyden and his colleagues used a similar approach to reduce crosstalk between fluorescent probes that directly image neurons’ membrane voltage. In parallel, they decided to try a similar approach with calcium imaging, which is a much more widely used technique.

To target GCaMP exclusively to cell bodies of neurons, the researchers tried fusing GCaMP to many different proteins. They explored two types of candidates — naturally occurring proteins that are known to accumulate in the cell body, and human-designed peptides — working with MIT biology Professor Amy Keating, who is also an author of the paper. These synthetic proteins are coiled-coil proteins, which have a distinctive structure in which multiple helices of the proteins coil together.  

Less crosstalk

The researchers screened about 30 candidates in neurons grown in lab dishes, and then chose two — one artificial coiled-coil and one naturally occurring peptide — to test in animals. Working with Misha Ahrens, who studies zebrafish at the Janelia Research Campus, they found that both proteins offered significant improvements over the original version of GCaMP. The signal-to-noise ratio — a measure of the strength of the signal compared to background activity — went up, and activity between adjacent neurons showed reduced correlation.

In studies of mice, performed in the lab of Xue Han at Boston University, the researchers also found that the new indicators reduced the correlations between activity of neighboring neurons. Additional studies using a miniature microscope (called a microendoscope), performed in the lab of Kay Tye at the Salk Institute for Biological Studies, revealed a significant increase in signal-to-noise ratio with the new indicators.

“Our new indicator makes the signals more accurate. This suggests that the signals that people are measuring with regular GCaMP could include crosstalk,” Boyden says. “There’s the possibility of artifactual synchrony between the cells.”

In all of the animal studies, they found that the artificial, coiled-coil protein produced a brighter signal than the naturally occurring peptide that they tested. Boyden says it’s unclear why the coiled-coil proteins work so well, but one possibility is that they bind to each other, making them less likely to travel very far within the cell.

Boyden hopes to use the new molecules to try to image the entire brains of small animals such as worms and fish, and his lab is also making the new indicators available to any researchers who want to use them.

“It should be very easy to implement, and in fact many groups are already using it,” Boyden says. “They can just use the regular microscopes that they already are using for calcium imaging, but instead of using the regular GCaMP molecule, they can substitute our new version.”

The research was primarily funded by the National Institute of Mental Health and the National Institute of Drug Abuse, as well as a Director’s Pioneer Award from the National Institutes of Health, and by Lisa Yang, John Doerr, the HHMI-Simons Faculty Scholars Program, and the Human Frontier Science Program.

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Improving global health equity by helping clinics do more with less

More children are being vaccinated around the world today than ever before, and the prevalence of many vaccine-preventable diseases has dropped over the last decade. Despite these encouraging signs, however, the availability of essential vaccines has stagnated globally in recent years, according the World Health Organization.

One problem, particularly in low-resource settings, is the difficulty of predicting how many children will show up for vaccinations at each health clinic. This leads to vaccine shortages, leaving children without critical immunizations, or to surpluses that can’t be used.

The startup macro-eyes is seeking to solve that problem with a vaccine forecasting tool that leverages a unique combination of real-time data sources, including new insights from front-line health workers. The company says the tool, named the Connected Health AI Network (CHAIN), was able to reduce vaccine wastage by 96 percent across three regions of Tanzania. Now it is working to scale that success across Tanzania and Mozambique.

“Health care is complex, and to be invited to the table, you need to deal with missing data,” says macro-eyes Chief Executive Officer Benjamin Fels, who co-founded the company with Suvrit Sra, the Esther and Harold E. Edgerton Career Development Associate Professor at MIT. “If your system needs age, gender, and weight to make predictions, but for one population you don’t have weight or age, you can’t just say, ‘This system doesn’t work.’ Our feeling is it has to be able to work in any setting.”

The company’s approach to prediction is already the basis for another product, the patient scheduling platform Sibyl, which has analyzed over 6 million hospital appointments and reduced wait times by more than 75 percent at one of the largest heart hospitals in the U.S. Sybil’s predictions work as part of CHAIN’s broader forecasts.

Both products represent steps toward macro-eyes’ larger goal of transforming health care through artificial intelligence. And by getting their solutions to work in the regions with the least amount of data, they’re also advancing the field of AI.

“The state of the art in machine learning will result from confronting fundamental challenges in the most difficult environments in the world,” Fels says. “Engage where the problems are hardest, and AI too will benefit: [It will become] smarter, faster, cheaper, and more resilient.”

Defining an approach

Sra and Fels first met about 10 years ago when Fels was working as an algorithmic trader for a hedge fund and Sra was a visiting faculty member at the University of California at Berkeley. The pair’s experience crunching numbers in different industries alerted them to a shortcoming in health care.

“A question that became an obsession to me was, ‘Why were financial markets almost entirely determined by machines — by algorithms — and health care the world over is probably the least algorithmic part of anybody’s life?’” Fels recalls. “Why is health care not more data-driven?”

Around 2013, the co-founders began building machine-learning algorithms that measured similarities between patients to better inform treatment plans at Stanford School of Medicine and another large academic medical center in New York. It was during that early work that the founders laid the foundation of the company’s approach.

“There are themes we established at Stanford that remain today,” Fels says. “One is [building systems with] humans in the loop: We’re not just learning from the data, we’re also learning from the experts. The other is multidimensionality. We’re not just looking at one type of data; we’re looking at 10 or 15 types, [including] images, time series, information about medication, dosage, financial information, how much it costs the patient or hospital.”

Around the time the founders began working with Stanford, Sra joined MIT’s Laboratory for Information and Decision Systems (LIDS) as a principal research scientist. He would go on to become a faculty member in the Department of Electrical Engineering and Computer Science and MIT’s Institute for Data, Systems, and Society (IDSS). The mission of IDSS, to advance fields including data science and to use those advances to improve society, aligned well with Sra’s mission at macro-eyes.

“Because of that focus [on impact] within IDSS, I find it my focus to try to do AI for social good,’ Sra says. “The true judgment of success is how many people did we help? How could we improve access to care for people, wherever they may be?”

In 2017, macro-eyes received a small grant from the Bill and Melinda Gates Foundation to explore the possibility of using data from front-line health workers to build a predictive supply chain for vaccines. It was the beginning of a relationship with the Gates Foundation that has steadily expanded as the company has reached new milestones, from building accurate vaccine utilization models in Tanzania and Mozambique to integrating with supply chains to make vaccine supplies more proactive. To help with the latter mission, Prashant Yadav recently joined the board of directors; Yadav worked as a professor of supply chain management with the MIT-Zaragoza International Logistics Program for seven years and is now a senior fellow at the Center for Global Development, a nonprofit thinktank.

In conjunction with their work on CHAIN, the company has deployed another product, Sibyl, which uses machine learning to determine when patients are most likely to show up for appointments, to help front-desk workers at health clinics build schedules. Fels says the system has allowed hospitals to improve the efficiency of their operations so much they’ve reduced the average time patients wait to see a doctor from 55 days to 13 days.

As a part of CHAIN, Sibyl similarly uses a range of data points to optimize schedules, allowing it to accurately predict behavior in environments where other machine learning models might struggle.

The founders are also exploring ways to apply that approach to help direct Covid-19 patients to health clinics with sufficient capacity. That work is being developed with Sierra Leone Chief Innovation Officer David Sengeh SM ’12 PhD ’16.

Pushing frontiers

Building solutions for some of the most underdeveloped health care systems in the world might seem like a difficult way for a young company to establish itself, but the approach is an extension of macro-eyes’ founding mission of building health care solutions that can benefit people around the world equally.

“As an organization, we can never assume data will be waiting for us,” Fels says. “We’ve learned that we need to think strategically and be thoughtful about how to access or generate the data we need to fulfill our mandate: Make the delivery of health care predictive, everywhere.”

The approach is also a good way to explore innovations in mathematical fields the founders have spent their careers working in.

“Necessity is absolutely the mother of invention,” Sra says. “This is innovation driven by need.”

And going forward, the company’s work in difficult environments should only make scaling easier.

“We think every day about how to make our technology more rapidly deployable, more generalizable, more highly scalable,” Sra says. “How do we get to the immense power of bringing true machine learning to the world’s most important problems without first spending decades and billions of dollars in building digital infrastructure? How do we leap into the future?”

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