Author: MIT News

Chemistry Undergraduate Teaching Lab hibernates fume hoods, drastically reducing energy costs

by Danielle Doughty | Department of Chemistry |

The Department of Chemistry’s state-of-the-art Undergraduate Teaching Lab (UGTL), which opened on the fifth floor of MIT.nano in fall 2018, is home to 69 fume hoods. The hoods, ranging from four to seven feet wide, protect students and staff from potential exposure to hazardous materials while working in the lab. Fume hoods represent a tremendous energy consumption on the MIT campus; in addition to the energy required to operate them, the air that replaces what is exhausted must be heated or cooled. Thus, any lab with a large number of fume hoods is destined to be faced with high operational energy cost.

“When the UGTL’s fume hoods are in use, the air-change rates — the number of times fresh air is exchanged in the space in a given time frame — averages between 25 and 30 air changes per hour (ACH),” says Nicole Imbergamo, senior sustainability project manager in MIT Campus Construction. “When the lab is unoccupied, that air-change rate averages 11 ACH. For context, in a laboratory with a single fume hood, typically MIT’s EHS [Environment, Health, and Safety] department would require six ACH when occupied and four ACH when unoccupied. Hibernation of the fume hoods allowed us to close the gap between the current unoccupied air-change rate and what is typical on campus in a non-teaching lab environment.”

Fifty-eight of the 69 fume hoods in the UGTL are consistently unused between the hours of 6:30 p.m. and 12 p.m., as well as all weekend long, totaling 135 hours per week. Based on these numbers, the team determined it was safe to “hibernate” the fume hoods during the off hours, saving the Institute on fan energy and the cost of heating and cooling the air that gets flushed into each hood.

John Dolhun PhD ’73 is the director of the UGTL. “The project started when MIT Green Labs — a division of the Environment, Health, and Safety Office now known as the Safe & Sustainable Labs Program — contacted the UGTL in October 2018, followed by an initial meeting in November 2018 with all the key players, including Safe and Sustainable Labs, the EHS Office, the Department of Facilities, and the Department of Chemistry,” says Dolhun. “It was during these initial discussions that the UGTL recognized this was something we had to do. The project was completed in April 2021.”

Now, through a scheduled time clock in the Building Management System (BMS), the 58 fume hoods are flipped into hibernation mode at the end of each day. “In hibernation mode, the exhaust air valves go to their minimum airflow, which is lower than a fume hood minimum required when in use,” says Imbergamo. “As a safety feature, if the sash of a fume hood is opened while it is in standby mode, the valve and hood are automatically released from hibernation until the next scheduled time.” The BMS allows Dolhun and all with access to instantly view the hibernation status of every hood online, at any time, from any location. As an additional safety measure, the lab is equipped with an emergency kill switch that, when activated, instantly takes all 58 fume hoods out of hibernation, increasing the air changes per hour by about 37 percent, at one touch.

The MIT operations team worked with the building controls vendor to create graphics that allow the UGTL users to easily see the hood sash positions and their current status as either hibernated or in normal operating mode. This virtual visibility allows the UGTL team to confirm the hoods are all closed before leaving the lab at the end of each day, and to confirm the energy reductions. This visual access also lends itself to educating the students on the importance of closing the sash at the end of their lab work, and gives an opportunity for educating the students on relevant fume hood management best practices that will serve them far beyond their undergraduate chemistry classes.

Since employing the use of hibernation mode, the unoccupied UGTL air change rate has plummeted from 11 ACH to seven ACH, drastically shrinking unnecessary energy outflow, saving MIT an estimated $21,000 per year. The annual utility cost savings of both reduced supply and exhaust fan energy, as well as the heating and cooling required of the supply air to the space, will result in a less-than three-year payback for MIT. The overall success of the hood hibernation program, and the savings that it has afforded the UGTL, is very motivational for the Green Initiative. The highlights of this system will be shared with other labs, both at MIT and beyond, that may also benefit from similar adjustments.

Machine learning discovers new sequences to boost drug delivery

by MIT Schwarzman College of Computing |

Duchenne muscular dystrophy (DMD), a rare genetic disease usually diagnosed in young boys, gradually weakens muscles across the body until the heart or lungs fail. Symptoms often show up by age 5; as the disease progresses, patients lose the ability to walk around age 12. Today, the average life expectancy for DMD patients hovers around 26.

It was big news, then, when Cambridge, Massachusetts-based Sarepta Therapeutics announced in 2019 a breakthrough drug that directly targets the mutated gene responsible for DMD. The therapy uses antisense phosphorodiamidate morpholino oligomers (PMO), a large synthetic molecule that permeates the cell nucleus in order to modify the dystrophin gene, allowing for production of a key protein that is normally missing in DMD patients. “But there’s a problem with PMO by itself. It’s not very good at entering cells,” says Carly Schissel, a PhD candidate in MIT’s Department of Chemistry.

To boost delivery to the nucleus, researchers can affix cell-penetrating peptides (CPPs) to the drug, thereby helping it cross the cell and nuclear membranes to reach its target. Which peptide sequence is best for the job, however, has remained a looming question.

MIT researchers have now developed a systematic approach to solving this problem by combining experimental chemistry with artificial intelligence to discover nontoxic, highly-active peptides that can be attached to PMO to aid delivery. By developing these novel sequences, they hope to rapidly accelerate the development of gene therapies for DMD and other diseases.

Results of their study have now been published in the journal Nature Chemistry in a paper led by Schissel and Somesh Mohapatra, a PhD student in the MIT Department of Materials Science and Engineering, who are the lead authors. Rafael Gomez-Bombarelli, assistant professor of materials science and engineering, and Bradley Pentelute, professor of chemistry, are the paper’s senior authors. Other authors include Justin Wolfe, Colin Fadzen, Kamela Bellovoda, Chia-Ling Wu, Jenna Wood, Annika Malmberg, and Andrei Loas.

“Proposing new peptides with a computer is not very hard. Judging if they’re good or not, this is what’s hard,” says Gomez-Bombarelli. “The key innovation is using machine learning to connect the sequence of a peptide, particularly a peptide that includes non-natural amino acids, to experimentally-measured biological activity.”

Dream data

CPPs are relatively short chains, made up of between five and 20 amino acids. While one CPP can have a positive impact on drug delivery, several linked together have a synergistic effect in carrying drugs over the finish line. These longer chains, containing 30 to 80 amino acids, are called miniproteins.

Before a model could make any worthwhile predictions, researchers on the experimental side needed to create a robust dataset. By mixing and matching 57 different peptides, Schissel and her colleagues were able to build a library of 600 miniproteins, each attached to PMO. With an assay, the team was able to quantify how well each miniprotein could move its cargo across the cell.

The decision to test the activity of each sequence, with PMO already attached, was important. Because any given drug will likely change the activity of a CPP sequence, it is difficult to repurpose existing data, and data generated in a single lab, on the same machines, by the same people, meet a gold standard for consistency in machine-learning datasets.

One goal of the project was to create a model that could work with any amino acid. While only 20 amino acids naturally occur in the human body, hundreds more exist elsewhere — like an amino acid expansion pack for drug development. To represent them in a machine-learning model, researchers typically use one-hot encoding, a method that assigns each component to a series of binary variables. Three amino acids, for example, would be represented as 100, 010, and 001. To add new amino acids, the number of variables would need to increase, meaning researchers would be stuck having to rebuild their model with each addition.

Instead, the team opted to represent amino acids with topological fingerprinting, which is essentially creating a unique barcode for each sequence, with each line in the barcode denoting either the presence or absence of a particular molecular substructure. “Even if the model has not seen [a sequence] before, we can represent it as a barcode, which is consistent with the rules that model has seen,” says Mohapatra, who led development efforts on the project. By using this system of representation, the researchers were able to expand their toolbox of possible sequences.

The team trained a convolutional neural network on the miniprotein library, with each of the 600 miniproteins labeled with its activity, indicating its ability to permeate the cell. Early on, the model proposed miniproteins laden with arginine, an amino acid that tears a hole in the cell membrane, which is not ideal to keep cells alive. To solve this issue, researchers used an optimizer to decentivize arginine, keeping the model from cheating.

In the end, the ability to interpret predictions proposed by the model was key. “It’s typically not enough to have a black box, because the models could be fixating on something that is not correct, or because it could be exploiting a phenomenon imperfectly,” Gomez-Bombarelli says.

In this case, researchers could overlay predictions generated by the model with the barcode representing sequence structure. “Doing that highlights certain regions that the model thinks play the biggest role in high activity,” Schissel says. “It’s not perfect, but it gives you focused regions to play around with. That information would definitely help us in the future to design new sequences empirically.”

Delivery boost

Ultimately, the machine-learning model proposed sequences that were more effective than any previously known variant. One in particular can boost PMO delivery by 50-fold. By injecting mice with these computer-suggested sequences, the researchers validated their predictions and demonstrated that the miniproteins are nontoxic.

It is too early to tell how this work will affect patients down the line, but better PMO delivery will be beneficial in several ways. If patients are exposed to lower levels of the drug, they may experience fewer side effects, for example, or require less-frequent doses (PMO is administered intravenously, often on a weekly basis). The treatment may also become less costly. As a testament to the concept, recent clinical trials demonstrated that a proprietary CPP from Sarepta Therapeutics could decrease exposure to PMO by 10-fold. Also, PMO is not the only drug that stands to be improved by miniproteins. In additional experiments, the model-generated miniproteins carried other functional proteins into the cell.

Noticing a disconnect between the work of machine-learning researchers and experimental chemists, Mohapatra has posted the model on GitHub, along with a tutorial for experimentalists who have their own list of sequences and activities. He notes that over a dozen people from across the world have adopted the model so far, repurposing it to make their own powerful predictions for a wide range of drugs.

The research was supported by the MIT Jameel Clinic, Sarepta Therapeutics, the MIT-SenseTime Alliance, and the National Science Foundation.

Gerald Wogan, professor emeritus of biological engineering, chemistry, and toxicology, dies at 91

by Department of Biological Engineering |

Gerald N. Wogan, the Underwood Prescott Professor of Biological Engineering, Chemistry, and Toxicology emeritus at MIT, passed away after a long illness on July 16 at the age of 91.

“Jerry” Wogan was a pioneering scientist who isolated, characterized, and established the mechanisms of action of many environmental toxins of great relevance to global public health. His leadership on aflatoxin research, a toxin that impacts the lives of billions of people, is a paradigm for environmental toxicology. His work ranged from basic mechanistic studies at the cell level to the development of animal models of disease, the study of disease patterns in populations, and, ultimately, the development of agents that induce biochemical pathways that protect people from toxin-induced disease.

During his 60-year career, Wogan trained over 75 graduate students and postdocs, who themselves went on to become leaders in the environmental health field. Former student John D. Groopman PhD ’79, who led environmental health sciences at Johns Hopkins University for 20 years, recalls: “While Jerry was a great scientific leader respected by his peers, it was his humanity and commitment to the translation of basic science to the public’s good that is his lasting legacy to his students and their students in turn.”

John Essigmann PhD ’76, the past director of the MIT Center for Environmental Health Sciences and associate head of chemistry, says, “Jerry was always open to new ideas and had a gift for taking an idea and projecting its impact on the global stage. He encouraged us to think big and see the broader impact of our work.”

Wogan was born in 1930 in the railroad town of Altoona, Pennsylvania. His father was a railroad worker, and Wogan decided to attend Juniata College in 1947 in part because his father had a company pass that allowed him to visit his son at school. Wogan worked his way through college as a truck driver and was a member of the Teamsters’ Union. In 1951, Wogan moved on to graduate work at the University of Illinois at Urbana, where he studied physiology, biochemistry, and microbiology with eminent physiologist Robert E. Anderson, and met his future wife, Holly, a special education teacher who became a surrogate parent to generations of Wogan lab members. The two married in 1957, the year Wogan received his PhD.

After his doctoral work and a brief teaching job at Rutgers University, Wogan sat by chance on an airplane next to Institute Professor emeritus Nevin Scrimshaw, recruiting faculty for what has become the MIT Department of Biological Engineering (Course 20). Wogan so impressed Scrimshaw during that flight that he was recruited to the MIT faculty and eventually took over as department head from 1979 to 1987.

In early work, Wogan and his longtime collaborator, chemist George Büchi, isolated a fungal toxin called aflatoxin B1 from peanuts infested with a fungus, Aspergillus flavus. In a chemistry and public health milestone, they identified the structure of the toxin and established methods for measuring it in foods and other environmental samples. The translation of this basic research to international policy and regulation of a potent carcinogen was a unique achievement that has impacted how the U.S. Food and Drug Administration, Environmental Protection Agency, and International Agency for Research on Cancer (IARC) evaluate potential carcinogens. Based on this research, Wogan participated in Volume 1 of the IARC evaluation of potential human carcinogens in 1972. This IARC program has become the gold standard for cancer risk assessment.

Wogan then turned to Southeast Asia, where he suspected that aflatoxin might be responsible for an epidemic of liver cancer. With Thai collaborators, Wogan and his student Ronald Shank ’59, PhD ’65 established an unequivocal association between aflatoxin levels in the food supply and the incidence of liver cancer in Thailand. Later replicated in sub-Saharan Africa and other parts of Asia, this aspect of his work represents a milestone in epidemiology.

Back at MIT, Büchi made derivatives of aflatoxin, and Wogan established animal models, some of which are still used today as pivotal tests for the cancer-causing potential of environmental agents. Wogan’s work on aflatoxin quickly expanded to other fungal and bacterial toxins, fossil fuel combustion products, toxic foodborne amines, and the important roles of infection inflammation as a cause and accelerant of cancer.

Regarding his work on persistent bacterial infections, collaborator Jim Fox comments: “Jerry’s collaborative studies with MIT colleagues Peter Dedon, John Essigmann, Steven Tannenbaum ’58, PhD ’62, and myself, probing the critical role of reactive oxygen species in the pathophysiology of chronic inflammation and carcinogenesis are unique, and I believe, extremely important.”

Collaborator Tannenbaum recalls, “Jerry Wogan invented the paradigm for discovering an environmental carcinogen, its metabolism into a DNA damaging agent, developing biomarkers for molecular epidemiology, and monoclonal antibodies for environmental surveillance. His team of graduate students led the way with his guidance and wound up with five faculty positions at top universities, where they continued to drive the field of cancer epidemiology.” Tannenbaum, who took the lead in establishing the Wogan Lectureship at MIT and went on to make pathfinding contributions on the roles of nitric oxide in human health and disease, also wrote that Wogan helped him as an early-career scientist move into toxicology.

The impact of Wogan’s work on aflatoxin was felt strongly across the globe, where up to 5 billion people are potentially exposed to the toxin each day. Mathuros Ruchirawat PhD ’75, vice president for research at the Chulabhorn Research Institute in Bangkok, reflects on the impact Wogan’s work had on global public health, research, and teaching in Southeast Asia: “His research has immense and long-lasting impacts on public health in Thailand; the increased public awareness of aflatoxins as a major risk factor for liver cancer has contributed to the prevention of this disease in the country.”

William Suk, who directs the national Superfund Research Program and plays a pivotal role in U.S.-Thailand relations, recalls that Jerry’s superb qualities as a scientist were complemented by his ability to mentor others: “I remember most his ability to provide sage advice to all.”

Three of Wogan’s past graduate students and two other MIT professors still teach at Bangkok every summer in a graduate degree program Wogan inspired to address capacity building in the developing world. Colleague Dedon says: “Jerry’s vision of science for the public good had true global impact that was much broader than the details of his research.”

Ram Sasisekharan, a co-founder of the Bangkok program, says: “Jerry was a true inspiration — focused on problems that need solutions, and was a bold take on complex global problems.”

Many of Wogan’s colleagues went off to apply their toxicology skills in the pharmaceutical arena.

Gerald McMahon, former president of Sugen and developer of several approved anticancer therapies, says: “Jerry’s inspiration and enthusiasm to take a risk and pursue innovation was inspiring and served me well in my biotech career.”

Another industry-based colleague, Alexander Wood, former executive director in the oncology department of Novartis Institutes for Biomedical Research and currently a senior lecturer in biological engineering at MIT, remembers Jerry as being “consistently engaged in a broad range of topics in the causation, prevention, and treatment of cancer, and cheerfully willing to offer sound advice and perspective.”

Wogan was recognized by many honors. He was a member of the U.S. National Academy of Sciences (1977) and the National Academy of Medicine (1994). He received the Charles S. Mott Prize of the General Motors Cancer Research Foundation (2005), the Medal of Honor of the International Agency for Research on Cancer (2010), The Princess Chulabhorn Gold Medal (2012), the Princess Takamatsu Cancer Research Fund award (2001), the Society of Toxicology lifetime scholar award (2004), the Chemical Industries Institute of Toxicology Founders’ award (1999), as well as distinguished alumnus awards from his alma maters, Juniata College (2010) and the University of Illinois (1995).

Wogan’s wife of over 50 years, Holly, passed away in 2013. He is survived by his daughter Christine and her husband John; his son Eugene and his wife Vicky; three grandchildren; and two great-grandchildren.

Former students Essigmann, Groopman, and Robert Croy PhD ’79 recently reminisced about the Wogan laboratory’s many adventures, which reflected Wogan’s belief that scientists should get out of the laboratory and experience the outside world. On one trip, the younger members of the Wogan-Büchi group crossed the 45-kilometer Pemigewasset Wilderness in New Hampshire’s White Mountains on skis, despite five feet of snow, brutal terrain, and subfreezing temperatures. As was typical of his style, Wogan had chilled champagne waiting at the finish of this long journey. He taught his group that hard work and a task well done are sweeter if one celebrates it in style. They also learned that their education at MIT was a journey, and that such journeys are best taken with friends. As a testimonial to this strategy of research group management, it is striking that so many of the former Wogan research groups are still close friends today, connected by the common bond of their time in his laboratory.

Wogan was a frequent participant in the Aspen Cancer Conference, which the Wogan family has designated as a charity for people who wish to donate in his name.

Five MIT School of Science professors receive tenure for 2021

by Annie Lee | School of Science |

MIT has granted tenure to five faculty members in the MIT School of Science in the departments of Brain and Cognitive Sciences, Chemistry, and Physics.

Physicist Joseph Checkelsky investigates exotic electronic states of matter through the synthesis, measurement, and control of solid-state materials. His research aims to uncover new physical phenomena that expand the boundaries of understanding of quantum mechanical condensed matter systems and open doorways to new technologies by realizing emergent electronic and magnetic functionalities. Checkelsky joined the Department of Physics in 2014 after a postdoc appointment at Japan’s Institute for Physical and Chemical Research and a lectureship at the University of Tokyo. He earned a bachelor’s degree in physics from Harvey Mudd College in 2004; and in 2010, he received a doctoral degree in physics from Princeton University.

A molecular neurobiologist and geneticist, Myriam Heiman studies the selective vulnerability and pathophysiology seen in neurodegenerative diseases of the brain’s basal ganglia, including Huntington’s disease and Parkinson’s disease. Using a revolutionary transcriptomic technique called translating ribosome affinity purification, she aims to understand the early molecular changes that eventually lead to cell death in these diseases. Heiman joined the Department of Brain and Cognitive Sciences, the Picower Institute for Learning and Memory, and the Broad Institute of Harvard and MIT in 2011 after completing her postdoctoral training at The Rockefeller University. She holds a PhD from Johns Hopkins University and a BA from Princeton University.

Particle physicist Kerstin Perez is interested in using cosmic particles to look beyond Standard Model physics, in particular evidence of dark matter interactions. Her work focuses on opening sensitivity to unexplored cosmic signatures with impact at the intersection of particle physics, astrophysics, and advanced instrumental techniques. Perez joined the Department of Physics in 2016, after a National Science Foundation astronomy and astrophysics postdoctoral fellowship at Columbia University and a faculty appointment at Haverford College. She earned her BA in physics from Columbia University in 2005, and her PhD from Caltech in 2011.

Alexander Radosevich works at the interface of inorganic and organic chemistry to design new chemical reactions. In particular, his interests concern the invention of compositionally new classes of molecular catalysts based on inexpensive and Earth-abundant elements of the p-block. This research explores the connection between molecular structure and reactivity in an effort to discover new efficient and sustainable approaches to chemical synthesis. Radosevich returned to the MIT Department of Chemistry, where he also held a postdoctoral appointment in 2016, after serving on the faculty at The Pennsylvania State University. He received a BS from the University of Notre Dame in 2002, and a PhD from University of California at Berkeley in 2007.

Alex K. Shalek creates and implements new experimental and computational approaches to identify the cellular and molecular features that inform tissue-level function and dysfunction across the spectrum of human health and disease. This encompasses both the development of broadly enabling technologies, such as Seq-Well, as well as their application to characterize, model, and rationally control complex multicellular systems. In addition to sharing this toolbox to empower mechanistic scientific inquiry across the global research community, Shalek is applying it to uncover principles that inform a wide range of problems in immunology, infectious diseases, and cancer. Shalek joined the Department of Chemistry and the Institute of Medical Engineering and Science in 2014 after postdoctoral training at Harvard University and the Broad Institute. He received his BA in chemical physics at Columbia University in 2004, followed by a PhD from Harvard University in 2011.

Ultralight material withstands supersonic microparticle impacts

by Jennifer Chu | MIT News Office |

A new study by engineers at MIT, Caltech, and ETH Zürich shows that “nanoarchitected” materials — materials designed from precisely patterned nanoscale structures — may be a promising route to lightweight armor, protective coatings, blast shields, and other impact-resistant materials.

The researchers have fabricated an ultralight material made from nanometer-scale carbon struts that give the material toughness and mechanical robustness. The team tested the material’s resilience by shooting it with microparticles at supersonic speeds, and found that the material, which is thinner than the width of a human hair, prevented the miniature projectiles from tearing through it.

The researchers calculate that compared with steel, Kevlar, aluminum, and other impact-resistant materials of comparable weight, the new material is more efficient at absorbing impacts.

“The same amount of mass of our material would be much more efficient at stopping a projectile than the same amount of mass of Kevlar,” says the study’s lead author, Carlos Portela, assistant professor of mechanical engineering at MIT.

If produced on a large scale, this and other nanoarchitected materials could potentially be designed as lighter, tougher alternatives to Kevlar and steel.

“The knowledge from this work… could provide design principles for ultra-lightweight impact resistant materials [for use in] efficient armor materials, protective coatings, and blast-resistant shields desirable in defense and space applications,” says co-author Julia R. Greer, a professor of materials science, mechanics, and medical engineering at Caltech, whose lab led the material’s fabrication.

The team, which reports its results today in the journal Nature Materials, includes David Veysset, Yuchen Sun, and Keith A. Nelson, of MIT’s Institute for Soldier Nanotechnologies and the Department of Chemistry, and Dennis M. Kochmann of ETH Zürich.

From brittle to bendy

A nanoarchitected material consists of patterned nanometer-scale structures that, depending on how they are arranged, can give materials unique properties such as exceptional lightness and resilience. As such, nanoarchitected materials are seen as potentially lighter, tougher impact-resistant materials. But this potential has largely been untested.

“We only know about their response in a slow-deformation regime, whereas a lot of their practical use is hypothesized to be in real-world applications where nothing deforms slowly,” Portela says.

The team set out to study nanoarchitected materials under conditions of fast deformation, such as during high-velocity impacts. At Caltech, they first fabricated a nanoarchitected material using two-photon lithography, a technique that uses a fast, high-powered laser to solidify microscopic structures in a photosensitive resin. The researchers constructed a repeating pattern known as a tetrakaidecahedron — a lattice configuration composed of microscopic struts.

“Historically this geometry appears in energy-mitigating foams,” says Portela, who chose to replicate this foam-like architecture in a carbon material at the nanoscale, to impart a flexible, impact-absorbing property to the normally stiff material. “While carbon is normally brittle, the arrangement and small sizes of the struts in the nanoarchitected material gives rise to a rubbery, bending-dominated architecture.”

After patterning the lattice structure, the researchers washed away the leftover resin and placed it in a high-temperature vacuum furnace to convert the polymer into carbon, leaving behind an ultralight, nanoarchitected carbon material.

Faster than the speed of sound

To test the material’s resilience to extreme deformation, the team performed microparticle impact experiments at MIT using laser-induced particle impact tests. The technique aims an ultrafast laser through a glass slide coated with a thin film of gold, which itself is coated with a layer of microparticles — in this case, 14-micron-wide silicon oxide particles. As the laser passes through the slide, it generates a plasma, or a rapid expansion of gas from the gold, which pushes the silicon oxide particles out in the direction of the laser. This causes the microparticles to rapidly accelerate toward the target.

The researchers can adjust the laser’s power to control the speed of the microparticle projectiles. In their experiments, they explored a range of microparticle velocities, from 40 to 1,100 meters per second, well within the supersonic range.

“Supersonic is anything above approximately 340 meters per second, which is the speed of sound in air at sea level,” Portela says. “So, some experiments achieved twice the speed of sound, easily.”

Using a high-speed camera, they captured videos of the microparticles making impact with the nanoarchitected material. They had fabricated material of two different densities — the less dense material had struts slightly thinner than the other. When they compared both materials’ impact response, they found the denser one was more resilient, and microparticles tended to embed in the material rather than tear straight through.

To get a closer look, the researchers carefully sliced through the embedded microparticles and the materials, and found in the region just below an embedded particle the microscopic struts and beams had crumpled and compacted in response to the impact, but the surrounding architecture remained intact.

collision at micro scale

collission at nanoscale

“We show the material can absorb a lot of energy because of this shock compaction mechanism of struts at the nanoscale, versus something that’s fully dense and monolithic, not nanoarchitected,” Portela says.

Interestingly, the team found they could predict the kind of damage the material would sustain by using a dimensional analysis framework for characterizing planetary impacts. Using a principle known as the Buckingham-Π theorem, this analysis accounts for various physical quantities, such as a meteor’s velocity and the strength of a planet’s surface material, to calculate a “cratering efficiency,” or the likelihood and extent to which a meteor will excavate a material.

When the team adapted the equation to the physical properties of their nanoarchitected film and the microparticles’ size and velocities, they found the framework could predict the kind of impacts that their experimental data showed.

Going forward, Portela says the framework can be used to predict the impact resilience of other nanoarchitected materials. He plans to explore various nanostructured configurations, as well as other materials beyond carbon, and ways to scale up their production — all with the goal of designing tougher, lighter protective materials.

“Nanoarchitected materials truly are promising as impact-mitigating materials,” Portela says. “There’s a lot we don’t know about them yet, and we’re starting this path to answering these questions and opening the door to their widespread applications.”

This research was supported, in part, by the U.S. Office of Naval Research, the Vannevar Bush Faculty Fellowship, and the U.S. Army Research Office through the Institute for Soldier Nanotechnologies at MIT.

Uncovering the mysteries of milk

by Hannah Meiseles | MIT News correspondent |

Sarah Nyquist got her first introduction to biology during high school, when she took an online MIT course taught by genomics pioneer Eric Lander. Initially unsure what to expect, she quickly discovered biology to be her favorite subject. She began experimenting with anything she could find, beginning with an old PCR machine and some dining hall vegetables.

Nyquist entered college as a biology major but soon gravitated toward the more hands-on style of the coursework in her computer science classes. Even as a computer science major and a two-time summer intern at Google, biology was never far from Nyquist’s mind. Her favorite class was taught by a computational biology professor: “It got me so excited to use computer science as a tool to interrogate biological questions,” she recalls.

During her last two years as an undergraduate at Rice University, Nyquist also worked in a lab at Baylor College of Medicine, eventually co-authoring a paper with Eric Lander himself.

Nyquist is now a PhD candidate studying computational and systems biology. Her work is co-advised by professors Alex Shalek and Bonnie Berger and uses machine learning to understand single-cell genomic data. Since this technology can be applied to nearly any living material, Nyquist was left to choose her focus.

After shifting between potential thesis ideas, Nyquist finally settled on studying lactation, an important and overlooked topic in human development. She and postdoc Brittany Goods are currently part of the MIT Milk Study, the first longitudinal study to profile the cells in human breast milk using single cell genomic data. “A lot of people don’t realize there’s actually live cells in breast milk. Our research is to see what the different cell types are and what they might be doing,” Nyquist says.

While she started out at MIT studying infectious diseases, Nyquist now enjoys investigating basic science questions about the reproductive health of people assigned female at birth. “Working on my dissertation has opened my eyes to this really important area of research. As a woman, I’ve always noticed a lot is unknown about female reproductive health,” she says. “The idea that I can contribute to that knowledge is really exciting to me.”

The complexities of milk

For her thesis, Nyquist and her team have sourced breast milk from over a dozen donors. These samples are provided immediately postpartum to around 40 weeks later, which provides insight into how breast milk changes over time. “We took record of the many changing environmental factors, such as if the child had started day care, if the mother had started menstruating, or if the mother had started hormonal birth control,” says Nyquist. “Any of these co-factors could explain the compositional changes we witnessed.”

Nyquist also hypothesized that discoveries about breast milk could be a proxy for studying breast tissue. Since breast tissue is necessary for lactation, researchers have been historically struggled to collect tissue samples. “A lot is unknown about the cellular composition of human breast tissue during lactation, even though it produces an important early source of nutrition,” she adds.

Overall, the team has found a lot of heterogeneity between donors, suggesting breast milk is more complicated than expected. They have witnessed that the cells in milk are composed primarily of a type of structural cells that increase in quantity over time. Her team hypothesized that this transformation could be due to the high turnover of breast epithelial tissue during breastfeeding. While the reasons are still unclear, their data add to the field’s previous understandings.

Other aspects of their findings have validated some early discoveries about important immune cells in breast milk. “We found a type of macrophage in human breast milk that other researchers have identified before in mouse breast tissue,” says Nyquist. “We were really excited that our results confirmed similar things they were seeing.”

Applying her research to Covid-19

In addition to studying cells in breast milk, Nyquist has applied her skills to studying organ cells that can be infected by Covid-19. The study began early into the pandemic, when Nyquist and her lab mates realized they could explore their lab’s collective cellular data in a new way. “We began looking to see if there were any cells that expressed genes that can be hijacked for cellular entry by the Covid-19 virus,” she says. “Sure enough, we found there are cells in nasal, lung, and gut tissues that are more susceptible to mediating viral entry.”

Their results were published and communicated to the public at a rapid speed. To Nyquist, this was evidence for how collaboration and computational tools are essential at producing next generation biological research. “I had never been on a project this fast-moving before — we were able to produce figures in just two weeks. I think it was encouraging to the public to see that scientists are working on this so quickly,” she says.

Outside of her own research, Nyquist enjoys mentoring and teaching other scientists. One of her favorite experiences was teaching coding at HSSP, a multiweekend program for middle and high schoolers, run by MIT students. The experience encouraged her to think of ways to make coding approachable to students of any background. “It can be challenging to figure out whether to message it as easy or hard, because either can scare people away. I try to get people excited enough to where they can learn the basics and build confidence to dive in further,” she says.

After graduation, Nyquist hopes to continue her love for mentoring by pursuing a career as a professor. She plans on deepening her research into uterine health, potentially by studying how different infectious diseases affect female reproductive tissues. Her goal is to provide greater insight about biological processes that have long been considered taboo.

“It’s crazy to me that we have so much more to learn about important topics like periods, breastfeeding, or menopause,” says Nyquist. “For example, we don’t understand how some medications impact people differently during pregnancy. Some doctors tell pregnant people to go off their antidepressants, because they worry it might affect their baby. In reality, there’s so much we don’t actually know.”

“When I tell people that this is my career direction, they often say that it’s hard to get funding for female reproductive health research, since it only affects 50 percent of the population,” she says.

“I think I can convince them to change their minds.”

Speeding up clinical trials by making drug production local

by Zach Winn | MIT News Office |

The Boston area has long been home to innovation that leads to impactful new drugs. But manufacturing those drugs for clinical trials often involves international partners and supply chains. The vulnerabilities of that system have become all too apparent during the Covid-19 pandemic.

Now Snapdragon Chemistry, co-founded by MIT Professor and Associate Provost Tim Jamison, is helping pharmaceutical companies manufacture drugs locally to shorten the time it takes for new drugs to get to patients.

Snapdragon essentially starts as a chemistry lab, running experiments on behalf of pharmaceutical customers to create molecules of interest. From there it seeks to automate production processes, often lessening the number of steps it takes to create those molecules. Sometimes the new process will require a technology — such as a specialized chemical reactor — the client doesn’t have, so Snapdragon builds the equipment for the client and teaches them to incorporate it into their processes.

Some of those reactors are being used for the commercial production of approved drugs, although most are designed to help pharmaceutical and biotech companies get through clinical trials more quickly.

“At the clinical stage, you just want to go as fast as possible to find out whether you have a useful therapeutic or not,” Snapdragon CEO Matt Bio says. “We’re really trying to stay focused on the technology for delivering drugs fast to the clinic.”

Snapdragon has worked with over 100 companies, ranging from small biotechs to large multinationals like Amgen, for whom it has helped develop potential cancer treatments. The company has also worked with research agencies to push the frontiers of automated material production, including in a project with the Biomedical Advanced Research and Development Authority (BARDA) to develop ribonucleotide triphosphates, which are the building blocks to mRNA-based Covid-19 vaccines.

In March, Snapdragon announced plans to build a 51,000 square foot facility in Waltham, Massachusetts, that will enable it to produce more drugs in-house, removing yet another step to get new drugs into the clinic.

“It’s about supplying the client with the fastest route possible to the molecule they need to test in the clinic,” Bio says.

By focusing on the processes and technology for synthesizing chemicals, the company believes it has potential to transform the economics of drug manufacturing at every scale.

“We can make [drugs] potentially a lot cheaper, and where that’s really interesting is [around questions like] how do you make a tuberculosis drug that’s, say, half a cent?” Bio says. “That’s a lot harder than making these complex drugs. But you need to save every penny if you’re going to roll out to parts of sub-Saharan Africa. Those are new opportunities we get to engage in.”

An idea, and a pivot

Jamison began thinking about starting a company when he noticed other scientists were interested in his research around continuous flow photochemistry, which uses light to spark chemical reactions and can offer huge cost and scale advantages over traditional chemistry processing done in batches.

“Generally, chemistry has been done since its origins in what we call batch mode,” says Jamison, who was also a principal investigator at the Novartis-MIT Center for Continuous Manufacturing and has published a number of papers around continuous flow chemistry processes. “It’s like cooking. We make a set quantity, that’s a batch. But if you’re going to be a food manufacturer, for example, you’d want something that’s continuous to meet the throughput, like an assembly line.”

In 2012, Jamison began mapping out what a company would look like with eventual co-founder Aaron Beeler, an associate professor of medicinal chemistry at Boston University.  After two years of developing, vetting, and “pressure testing” their business model by seeking guidance from colleagues in their networks and MIT’s Venture Mentoring Service, the founders set out to start a company that would manufacture specialty and fine chemicals, focusing on those that would be well-suited to continuous flow synthesis. Snapdragon officially formed in October 2014 as Firefly Therapeutics.

Jamison likes to say the company pivoted on day one. Within a week of incorporating, the founders had secured two contracts — not to sell chemicals, but to help pharmaceutical companies develop continuous manufacturing processes.

Bio joined in 2015 at a time when the company — by then renamed Snapdragon — had secured consulting and services contracts. Snapdragon’s customer base was growing so rapidly by then the company moved four times in the first four years as it went from needing one lab bench to dozens.

Snapdragon’s work helping companies improve chemistry processes is still its most common service offering. Most of those improvements come from an understanding of what the latest reactor and automation technology can offer.

“If you walked around our labs, you’d see a lot of automation and robotics that are doing things that people used to do less efficiently,” Bio says. “Instead of our scientists being in the lab setting up a reaction, breaking down a reaction, they can just think about the chemistry and then use some of the robotic tools to get the answers they want faster.”

“One area where Snapdragon is really innovating is in lab [operating systems], which are a way of networking literally every single instrument in the company and gathering real-time information about processes,” Jamison says.

Fulfilling an industry’s potential

Snapdragon’s Waltham expansion will bring the company full circle, to the cofounders’ original idea of producing specialty chemicals in-house.

Bio says the expansion will be particularly beneficial for developing treatments to diseases with smaller patient populations and smaller material requirements. He notes that in some mRNA-based treatments, for example, a kilogram of material can treat millions of people.

The company also recently received a grant from DARPA to try turning plentiful commodities in the U.S., like natural gas and crop waste, into the starting materials for high-value pharmaceuticals.

Moving forward, Jamison thinks Snapdragon’s machine-based production processes will only accelerate the company’s ability to innovate.

“Chemistry of the future could be very different from what we’re doing right now, but we don’t have enough data yet,” Jamison says. “One of the longer-term visions for Snapdragon is creating automated systems capable of generating lots of data, and then using those data as training sets for machine learning algorithms toward any number of applications, from how to make something to predicting properties of materials. That unlocks a lot of exciting possibilities.”

QS ranks MIT the world’s No. 1 university for 2021-22

by MIT News Office |

MIT has again been named the world’s top university by the QS World University Rankings, which were announced today. This is the 10th year in a row MIT has received this distinction.

The full 2022 edition of the rankings — published by Quacquarelli Symonds, an organization specializing in education and study abroad — can be found at TopUniversities.com. The QS rankings were based on academic reputation, employer reputation, citations per faculty, student-to-faculty ratio, proportion of international faculty, and proportion of international students.

MIT was also ranked the world’s top university in 12 of the subject areas ranked by QS, as announced in March of this year.

The Institute received a No. 1 ranking in the following QS subject areas: Architecture; Chemistry; Computer Science and Information Systems; Chemical Engineering; Civil and Structural Engineering; Economics and Econometrics; Electrical and Electronic Engineering; Mechanical, Aeronautical and Manufacturing Engineering; Linguistics; Mathematics; Physics and Astronomy; and Statistics and Operational Research.

MIT also placed second in four subject areas: Accounting and Finance; Biological Sciences; Earth and Marine Sciences; and Materials Science.

“We deeply appreciate the recognition of our institution and the faculty, staff, alumni, and students that make MIT what it is — and we also tremendously admire the achievements of academic institutions around the globe,” says MIT President L. Rafael Reif. “The world benefits from a strong higher education network that delivers countless benefits for humanity, from fundamental discoveries to novel solutions to pressing challenges in climate and health, to the education of the next generation of talent. We are proud and grateful to belong to this great human community of scholars, researchers, and educators, striving together to make a better world.”

How metals work together to weaken hardy nitrogen-nitrogen bonds

by Anne Trafton | MIT News Office |

Nitrogen, an element that is essential for all living cells, makes up about 78 percent of Earth’s atmosphere. However, most organisms cannot make use of this nitrogen until it is converted into ammonia. Until humans invented industrial processes for ammonia synthesis, almost all ammonia on the planet was generated by microbes using nitrogenases, the only enzymes that can break the nitrogen-nitrogen bond found in gaseous dinitrogen, or N2.

These enzymes contain clusters of metal and sulfur atoms that help perform this critical reaction, but the mechanism of how they do so is not well-understood. For the first time, MIT chemists have now determined the structure of a complex that forms when N2 binds to these clusters, and they discovered that the clusters are able to weaken the nitrogen-nitrogen bond to a surprising extent.

“This study enables us to gain insights into the mechanism that allows you to activate this really inert molecule, which has a very strong bond that is difficult to break,” says Daniel Suess, the Class of ’48 Career Development Assistant Professor of Chemistry at MIT and the senior author of the study.

Alex McSkimming, a former MIT postdoc who is now an assistant professor at Tulane University, is the lead author of the paper, which appears today in Nature Chemistry.

Nitrogen fixation

Nitrogen is a critical component of proteins, DNA, and other biological molecules. To extract nitrogen from the atmosphere, early microbes evolved nitrogenases, which convert nitrogen gas to ammonia (NH3) through a process called nitrogen fixation. Cells can then use this ammonia to build more complex nitrogen-containing compounds.

“The ability to access fixed nitrogen on large scales has been instrumental in enabling the proliferation of life,” Suess says. “Dinitrogen has a really strong bond and is really unreactive, so chemists basically consider it an inert molecule. It’s a puzzle that life had to figure out: how to convert this inert molecule into useful chemical species.”

All nitrogenases contain a cluster of iron and sulfur atoms, and some of them also include molybdenum. Dinitrogen is believed to bind to these clusters to initiate the conversion to ammonia. However, the nature of this interaction is unclear, and until now, scientists had not been able to characterize N2 binding to an iron-sulfur cluster.

To shed light on how nitrogenases bind N2, chemists have designed simpler versions of iron-sulfur clusters that they can use to model the naturally occurring clusters. The most active nitrogenase uses an iron-sulfur cluster with seven iron atoms, nine sulfur atoms, a molybdenum atom, and a carbon atom. For this study, the MIT team created one that has three iron atoms, four sulfur atoms, a molybdenum atom, and no carbon.

One challenge in trying to mimic the natural binding of dinitrogen to the iron-sulfur cluster is that when the clusters are in a solution, they can react with themselves instead of binding substrates such as dinitrogen. To overcome that, Suess and his students created a protective environment around the cluster by attaching chemical groups called ligands.

The researchers attached one ligand to each of the metal atoms except for one iron atom, which is where N2 binds to the cluster. These ligands prevent unwanted reactions and allow dinitrogen to enter the cluster and bind to one of the iron atoms. Once this binding occurred, the researchers were able to determine the structure of the complex using X-ray crystallography and other techniques.

They also found that the triple bond between the two nitrogen atoms of N2 is weakened to a surprising extent. This weakening occurs when the iron atoms transfer much of their electron density to the nitrogen-nitrogen bond, which makes the bond much less stable.

Cluster cooperation

Another surprising finding was that all of the metal atoms in the cluster contribute to this electron transfer, not only the iron atom to which the dinitrogen is bound.

“That suggests that these clusters can electronically cooperate to activate this inert bond,” Suess says. “The nitrogen-nitrogen bond can be weakened by iron atoms that wouldn’t otherwise weaken it. Because they’re in a cluster, they can do it cooperatively.”

The findings represent “a significant milestone in iron-sulfur cluster chemistry,” says Theodore Betley, chair of the Department of Chemistry and Chemical Biology at Harvard University, who was not involved in the study.

“Although the nitrogenase enzymes known to fix atmospheric nitrogen are composed of fused iron-sulfur clusters, synthetic chemists have never, until now, been able to demonstrate dinitrogen uptake using synthetic analogues,” Betley says. “This work is a major advance for the iron-sulfur cluster community and bioinorganic chemists at large. More than anything, this advance has shown that iron-sulfur clusters have a rich reaction chemistry yet to be discovered.”

The researchers’ findings also confirmed that simpler versions of the iron-sulfur cluster, such as those they created for this study, can effectively weaken the nitrogen-nitrogen bond. The earliest microbes to develop the ability to fix nitrogen may have evolved similar types of simple clusters, Suess says.

Suess and his students are now working on ways to study how the more complex, naturally occurring versions of iron-sulfur clusters interact with dinitrogen.

The research was funded by the MIT Research Support Committee Fund.

MIT turns “magic” material into versatile electronic devices

by Elizabeth A. Thomson | Materials Research Laboratory |

MIT researchers and colleagues have turned a “magic” material composed of atomically thin layers of carbon into three useful electronic devices. Normally, such devices, all key to the quantum electronics industry, are created using a variety of materials that require multiple fabrication steps. The MIT approach automatically solves a variety of problems associated with those more complicated processes.

As a result, the work could usher in a new generation of quantum electronic devices for applications including quantum computing. Further, the devices can be superconducting, or conduct electricity without resistance. They do so, however, through an unconventional mechanism that, with further study, could give new insights into the physics of superconductivity. The researchers report their results in the May 3 issue of Nature Nanotechnology.

“In this work we have demonstrated that magic-angle graphene is the most versatile of all superconducting materials, allowing us to realize in a single system a multitude of quantum electronic devices. Using this advanced platform, we have been able to explore for the first time novel superconducting physics that only appears in two dimensions,” says Pablo Jarillo-Herrero, the Cecil and Ida Green Professor of Physics at MIT and leader of the work. Jarillo-Herrero is also affiliated with MIT’s Materials Research Laboratory.

A magic angle

The new “magic” material is based on graphene, a single layer of carbon atoms arranged in hexagons resembling a honeycomb structure. Since the first unambiguous isolation of graphene in 2004, interest in this material has skyrocketed due to its unique properties. For example, it is stronger than diamond, transparent, and flexible. It also easily conducts both heat and electricity.

In 2018, the Jarillo-Herrero group made a startling discovery involving two layers of graphene, one placed on top of the other. Those layers, however, weren’t exactly on top of each other; rather, one was slightly rotated at a “magic angle” of 1.1 degrees.

The resulting structure allowed the graphene to be either a superconductor or an insulator (which prevents the flow of electrical current), depending on the number of electrons in the system as provided by an electric field. Essentially, the team was able to tune graphene into completely different states by changing the voltage at the turn of a knob.

The overall “magic” material, formally known as magic-angle twisted bilayer graphene (MATBG), has generated intense interest in the research community, even inspiring a new field known as twistronics. It is also at the heart of the current work.

In 2018, Jarillo-Herrero and coworkers changed the voltage supplied to the magic material via a single electrode, or metallic gate. In the current work, “we introduced multiple gates to subject different areas of the material to different electric fields,” says Daniel Rodan-Legrain, a graduate student in physics and lead author of the Nature Nanotechnology paper.

Suddenly, the team was able to tune different sections of the same magic material into a plethora of electronic states, from superconducting to insulating to somewhere in between. Then, by applying gates in different configurations, they were able to reproduce all of the parts of an electronic circuit that would ordinarily be created with completely different materials.

Working devices

Ultimately, the team used this approach to create three different working quantum electronic devices. These devices include a Josephson junction, or superconducting switch. Josephson junctions are the building blocks of the quantum bits, or qubits, behind superconducting quantum computers. They also have a variety of other applications, such as incorporation into devices that can make very precise measurements of magnetic fields.

The team also created two related devices: a spectroscopic tunneling device and a single-electron transistor, or a very sensitive device for controlling the movement of electricity, literally one electron at a time. The former is key to studying superconductivity, while the latter has a variety of applications, in part because of its extreme sensitivity to electric fields.

All three devices benefit from being made of a single electrically tunable material. Those made conventionally, of multiple materials, suffer from a variety of challenges. For example, different materials may be incompatible. “Now, if you’re dealing with one single material, those problems disappear,” says Rodan-Legrain.

William Oliver, an MIT associate professor in the Department of Electrical Engineering and Computer Science who was not involved in the research, says: “MATBG has the remarkable property that its electrical properties — metallic, superconducting, insulating, etc. — can be determined by applying a voltage to a nearby gate. In this work, Rodan-Legrain et al. have shown that they can make rather complicated devices comprising superconducting, normal, and insulating regions by electrical gating of a single flake of MATBG. The conventional approach would be to fabricate the device in several steps using different materials. With MATBG, the resulting devices are fully reconfigurable by simply changing the gate voltages.”

Toward the future

The work described in the Nature Nanotechnology paper paves the way for many potential future advances. For example, says Rodan-Legrain, it could be used to create the first voltage-tunable qubit from a single material, which could be applied in future quantum computers.

In addition, because the new system enables more detailed studies of the enigmatic superconductivity in MATBG, and is relatively easy to work with, the team is hopeful that it could allow insights into the creation of high-temperature superconductors. Current superconductors can only operate at very low temperatures. “That is actually one of the big hopes [behind our magic material],” says Rodan-Legrain. “Can we use it as a kind of Rosetta Stone” to better understand its high-temperature cousins?

In a glimpse into how science works, Rodan-Legrain describes the surprises the team encountered while conducting the research. For example, some of the data from the experiments didn’t correspond to the team’s initial expectations. That’s because the Josephson junctions they created using atomically thin MATGB were two-dimensional, and thus had a notably different behavior from their 3D conventional counterparts. “It was great having the data come through, seeing them, being puzzled about them, and then further understanding and making sense of what we saw.”

In addition to Jarillo-Herrero and Rodan-Legrain, additional authors of the paper are Yuan Cao, a postdoc in MIT’s Materials Research Laboratory (MRL); Jeong Min Park, a graduate student in the Department of Chemistry; Sergio C. de la Barrera, a postdoc in the MRL; Mallika T. Randeria, a Pappalardo Postdoctoral Fellow in the Department of Physics; and Kenji Watanabe and Takashi Taniguchi, both of the National Institute for Materials Science in Japan. (Rodan-Legrain, Cao, and Park were equal contributors to the paper.)

This work was supported by the U.S. National Science Foundation, the U.S. Department of Energy, the U.S. Army Research Office, the Fundació Bancaria “la Caixa,” the Gordon and Betty Moore Foundation, the Fundación Ramon Areces, an MIT Pappalardo Fellowship, and the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.