Author: MIT News

Notation system allows scientists to communicate polymers more easily

by Melanie Miller Kaufman |

Having a compact, yet robust, structurally-based identifier or representation system for molecular structures is a key enabling factor for efficient sharing and dissemination of results within the research community. Such systems also lay down the essential foundations for machine learning and other data-driven research. While substantial advances have been made for small molecules, the polymer community has struggled in coming up with an efficient representation system.

For small molecules, the basic premise is that each distinct chemical species corresponds to a well-defined chemical structure. This does not hold for polymers. Polymers are intrinsically stochastic molecules that are often ensembles with a distribution of chemical structures. This difficulty limits the applicability of all deterministic representations developed for small molecules. In a paper published Sept. 12 in ACS Central Science, researchers at MIT, Duke University, and Northwestern University report a new representation system that is capable of handling the stochastic nature of polymers, called BigSMILES.

“BigSMILES addresses a significant challenge in the digital representation of polymers,” explains Connor Coley PhD ’19, co-author of the paper. “Polymers are almost always ensembles of multiple chemical structures, generated through stochastic processes, so we can’t use the same strategies for writing down their structures as for small molecules.”

Co-authors are Coley; associate professor of chemical engineering Bradley D. Olsen at MIT; Warren K. Lewis Professor of Chemical Engineering Klavs F. Jensen at MIT; assistant professor of chemistry Julia A. Kalow at Northwestern University; associate professor of chemistry Jeremiah A. Johnson at MIT; William T. Miller Professor of Chemistry Stephen L. Craig at Duke University; graduate student Eliot Woods at Northwestern University; graduate student Zi Wang at Duke University; graduate student Wencong Wang at MIT; graduate student Haley K. Beech at MIT; visiting researcher Hidenobu Mochigase at MIT; and graduate student Tzyy-Shyang Lin at MIT.

There are several line notations to communicate molecular structure, with simplified molecular-input line-entry system (SMILES) being the most popular. SMILES is generally considered the most human-readable variant, with by far the widest software support. In practice, SMILES provides a simple set of representations that are suitable as labels for chemical data and as a memory-compact identifier for data exchange between researchers. As a text-based system, SMILES is also a natural fit to many text-based machine learning algorithms. These characteristics have made SMILES a perfect tool for translating chemistry knowledge into a machine-friendly form, and it has been successfully applied for small molecule property prediction and computer-aided synthesis planning.

Polymers, however, have resisted description by this and other structural languages. This is because most structural languages such as SMILES have been designed to describe molecules or chemical fragments that are well-defined atomistic graphs. Since polymers are stochastic molecules, they do not have unique SMILES representations. This lack of a unified naming or identifier convention for polymer materials is one of the major hurdles slowing down the development of the polymer informatics field. While pioneering efforts on polymer informatics, such as the Polymer Genome Project, have demonstrated the usefulness of SMILES extensions in polymer informatics, the fast development of new chemistry and the rapid development of materials informatics and data-driven research make the need for a universally applicable naming convention for polymers important.

“Machine learning presents an enormous opportunity to accelerate chemical development and discovery,” says Lin He, acting deputy division director for the National Science Foundation (NSF) Division of Chemistry. “This expanded tool to label structures, specifically devised to address the unique challenges inherent to polymers, greatly enhances the searchability of chemical structural data, and brings us one step closer to harnessing the data revolution.”

The researchers have created a new structurally-based construct as an addition to the highly successful SMILES representation that can treat the random nature of polymer materials. Since polymers are high molar mass molecules, this construct is named BigSMILES. In BigSMILES, polymeric fragments are represented by a list of repeating units enclosed by curly brackets. The chemical structures of the repeating units are encoded using normal SMILES syntax, but with additional bonding descriptors that specify how different repeating units are connected to form polymers. This simple design of syntax would enable the encoding of macromolecules over a wide range of different chemistries, including homopolymer, random copolymers and block copolymers, and a variety of molecular connectivity, ranging from linear polymers to ring polymers to even branched polymers. As in SMILES, BigSMILES representations are compact, self-contained text strings.

“Standardizing the digital representation of polymeric structures with BigSMILES will encourage the sharing and aggregation of polymer data, improving model quality over time and reinforcing the benefits of its use,” says Jason Clark, the materials lead in Open Innovation for Renewable Chemicals and Materials at Braskem, who was not associated with the research. “BigSMILES is a significant contribution to the field in that it addresses the need for a flexible system to represent complex polymer structures digitally.”

Clark adds, “The challenges faced by the plastics industry in the context of the circular economy begins with the source of raw materials and continues all the way through end-of-life management. Addressing these challenges requires the innovative design of polymer-based materials, which has traditionally suffered from lengthy development cycles. Advances in artificial intelligence and machine learning have shown promise to accelerate the development cycle for applications utilizing metal alloys and small organic molecules, motivating the plastics industry to seek a parallel approach.” BigSMILES digital representations facilitate the evaluation of structure-performance relationships by application of data science methods, he says, ultimately accelerating the convergence to the polymer structures or compositions that will help enable the circular economy.

“A multitude of complicated polymer structures can be constructed through the composition of three new basic operators and original SMILES symbols,” says Olsen, “Entire fields of chemistry, materials science, and engineering, including polymer science, biomaterials, materials chemistry, and much of biochemistry, are based upon macromolecules which have stochastic structures. This can basically be thought of as a new language for how to write the structure of large molecules.”

“One of the things I’m excited about is how the data entry might eventually be tied directly to the synthetic methods used to make a particular polymer,” says Craig, “Because of that, there is an opportunity to actually capture and process more information about the molecules than is typically available from standard characterizations. If this can be done, it will enable all sorts of discoveries.”

This work was funded by the NSF through the Center for the Chemistry of Molecularly Optimized Networks, an NSF Center for Chemical Innovation.

Jesús Dones-Monroig: Creating space for everyone in chemistry

by Daysia Tolentino | MIT News correspondent |

Growing up on a large swath of land in Puerto Rico, Jesús Dones-Monroig was always playing in nature. He was encouraged to plant, build, and explore the environment around his home. His father even took him to the ocean to go spearfishing, where he developed a fascination for marine life. He credits a lot of his curiosity of nature to his parents, who encouraged Dones-Monroig and his siblings to play outdoors.

“[My parents] let us be free to do whatever we wanted out there. They gave us the freedom to have an idea and play with things outside to make it happen,” says Dones-Monroig.

Eventually, this affinity with the natural world would contribute to Dones-Monroig’s interest in biology and organic chemistry. He went on to study chemistry at the University of Puerto Rico at Rio Piedras and was particularly inspired by his organic chemistry professor, Ingrid Montes, to appreciate the world through a molecular level.

Now a fifth year PhD student in the Department of Chemistry, Dones-Monroig works in the lab of Ronald Raines, the Roger and Georges Firmenich Professor of Natural Product Chemistry, and studies collagen mimetic peptides, or “CMPs.” Dones-Monroig has developed a CMP that can selectively anneal with damaged collagen. At this stage, he is working on optimizing his newly developed CMP to help detect mammalian collagen that has suffered damage. In the future, he hopes to develop a system that selectively anneals to different types of damaged collagen.

As a chemical biologist, Dones-Monroig also works on synthetic chemistry projects, from developing synthetic peptides through organic chemistry to synthesizing faster and more selective organic molecules for “click chemistry.”

“That’s why I love research in the Raines Lab,” Dones-Monroig says, “You’re not restricted to one area of chemistry.”

Promoting diversity and inclusion

Dones-Monroig is a family-driven, community-oriented person, and being so far from home has motivated him to create connections and support groups at MIT. He also feels strongly that without the right support, students can’t fully realize their potential in their academic and professional pursuits.

While pursuing his masters in chemical biology at the University of Wisconsin at Madison, Dones-Monroig was involved in programs that promote diversity and inclusion. Coming to MIT, he felt there was a lack of support for underrepresented and underserved graduate and undergraduate students at the Institute. With the help of professor and former head of the Department of Chemistry Tim Jamison, as well as individuals in the Women in Chemistry (WIC) group and the Chemistry Graduate Student Committee (CGSC), Dones-Monroig founded the Chemistry Alliance for Diversity and Inclusion (CADI).

Launched in 2018, CADI seeks to support the success of underrepresented and underserved graduate and undergraduate students in the chemistry department and to help ensure that the campus has safe, inclusive, and supportive environments for students. The group facilitates conversations regarding the state of diversity in the field of chemistry and provides students with professional and academic resources. Finding community in graduate school can be just as important as the classes one takes or the skills one acquires, Dones-Monroig says.

“If we are not given support at a personal level, our educational and professional potential is going to be directly affected. CADI is for anybody that doesn’t feel part of the chemistry department,” he says.

Dones-Monroig also serves as a pod leader for the MIT Summer Research Program (MSRP), a program that aims to promote the value of graduate education and improve the research enterprise through increased diversity in MIT.

“The students that come to this program are astounding. They’re very intelligent and driven, but they may not have the same resources as MIT in their home universities. So we welcome them,” says Dones-Monroig.

Continuing with his penchant for mentorship, Dones-Monroig will serve as a graduate resident advisor (GRA) at the MIT Student House. He will be a mentor to the international undergraduate and graduate students that live there.

Healthy bodies, healthy minds

Outside of his research, Dones-Monroig stays quite active and enjoys sports. He plays on MIT’s intramural basketball team, and he also enjoys volleyball, tennis, and surfing. Perhaps most impressively, he participates in the Spartan Races, which are races that range in length and feature a variety of physical obstacles. Next month, he will be doing an Ultra-Spartan Race on Killington Peak in Vermont, where he will go through 60 obstacles over the course of 30 miles.

For Dones-Monroig, exercise allows him to reduce stress and focus on something other than his research. He attributes his good health, mentally and physically, to staying active. This mentality is from his 61-year-old father, who still tries to run races against him, Dones-Monroig jokes.

“If you have a mindset of keeping your body as healthy as your mind, you’ll be more productive. I train my mind in the lab and come out and train my body outside,” says Dones-Monroig.

While Dones-Monroig clearly works hard, he plays hard too, and loves to dance salsa on the weekends. With friends that he has made in the local Puerto Rican community, Dones-Monroig goes out to dance and socialize at La Fábrica in Central Square.

“I think I’m decent at salsa,” Dones-Monroig laughs, adding, “When compared to non-salsa dancers, then I’m good!”

Mentorship and scholarship keep summer biology research program strong

by Laura Carter | School of Science |

When you get a call offering you the chance to get involved in research at MIT, says Squire Booker PhD ’94, as he did when he was a student back home in Beaumont, Texas, with no summer plans, you don’t say no. This is how he joined seven other students from around the United States as the first class in the MIT Student Research Program (MSRP), even though the start date was only days away. “I was given the opportunity to get out of Texas, the opportunity to go to a big cosmopolitan city, the opportunity to go to MIT. So, I got a plane ticket and flew up a few days later,” says Booker.

Thirty-three summers later, back on campus to deliver the doctoral graduation ceremony speech, where he had lunch with several current members and fellow alumni of the program, Booker insists that he has no regrets with his decision.

Booker was one of three from that inaugural class who remained at MIT to pursue a PhD to continue the research he started during the program. He was incredibly fortunate, he notes, to get a “perfect match” placement, working with former professors of biology Bill Johnson and Chris Walsh on a project that aligned with his interests of combining chemistry and biology. He didn’t have much more of an idea of his preferred area of study than that.

Prior to arriving at MIT, given the lack of exposure to science, he didn’t know what research entailed, or what scientists did every day. But he says he quickly fell in love with the subject and his research group, even joining their summer lab softball team.

Although Walsh left MIT the year Booker was accepted as a PhD student, he easily shifted into the lab of Novartis Professor of Chemistry Emeritus JoAnne Stubbe, a new faculty member at the time, who was also working on the interface of chemistry and biology and provided the amount of hands-on support he needed as a new graduate student. “Ever since leaving the lab, she’s been my number one supporter,” he says of Stubbe.

Stubbe and her research inspired the direction Booker’s education took. He continues to conduct research revolving around proteins and catalysis reactions as a professor at Penn State University and a principal investigator with the Howard Hughes Medical Institute. Now, he heads a large lab group himself.

From mentee to mentor

Booker oversees an average of 10 group members at any given time, not including undergraduate students. Like his mentor, he tries to be very hands-on, resorting to email when he’s traveling — which is often. He admitted with a chuckle that his students keep track of where he is at any given time by following his Twitter account. Always trying to find ways to include motivated students who approach him about contributing to his research, the only time Booker turns them away is for their benefit — if they have a full course load and additional time on research will overload their schedules. He even considers high school students.

The first high school student to join his lab was Martin McLaughlin ’15, who Booker describes fondly as “aggressively motivated” and “trembling with excitement to do research.” Within the first week, McLaughlin was taking the initiative to use his lunch breaks from school to bike to Booker’s lab. Martin’s results, which were published in Science in collaboration with Professor Cathy Drennan in the MIT Department of Biology, introduced Booker into a new niche: crystallography.

When McLaughlin asked to continue working on the discovery with Drennan as an undergraduate at MIT, he didn’t hesitate to agree. McLaughlin had moved into Drennan’s lab a week into his first semester.

Research for all

Not all students share this drive to delve into research. Like Booker himself, many aren’t even aware of possibilities to get involved in science and consider a career in research. It’s still hard, he says, even though “people are more serious about this diversity thing,” as he calls it, than when he was first starting his education.

Booker tries to reach out, especially to other minority students, through several programs, much like the MSRP, an invaluable program. While on campus this past spring, Booker met with current and past MSRP students.

One of those students was Jeandele Elliot, a chemical engineering student at Howard University from Saint Lucia in the Caribbean, who is working in the Jing-Ke Weng Lab in the Department of Biology this summer on a molecule that can protect pollen grains. For her, meeting Booker was another connection the program affords her. “The MSRP program has been beneficial to me in a special way since it has connected me with people I can really relate to,” she said.

The advice he gave to Elliot, and the others in the same position he was in once, was to prepare for exciting careers. The program is not just a steppingstone into research, he proclaimed, but it places participants with the best mentors and being privy to the best frontiers. Booker was delighted that some of the 25 current and past participants then attended MIT for graduate school as he did.

Tsehai A.J. Grell PhD ’18, a current chemistry graduate student in Drennan’s research group and an alumnus of MSRP, calls Squire Booker a “labhold” name — a household name in the lab. “As an African-American professor of biochemistry, an alumnus of my department, and a leader in my field, he instantly became one of my role models,” Grell said. “This was further solidified when I found out that he was a part of the first cohort of MSRP students, the summer research program which is responsible for me enrolling in MIT’s graduate program.”

Grell reminisced on his experience and the spring luncheon with Booker. “Because MSRP was such a foundational experience in my career, I am always enthused to interact with the current MSRP cohort and to encourage them to make the most of this opportunity, as it can be a pivotal summer in their careers,” says Grell. In addition, he said, “the excitement of the students is palpable and contagious. It reenergizes me and gives me purpose.”

Elliott, Grell, and Booker are three of more than 800 students from institutions with limited research opportunities who have participated in the MSRP, which was divided into two subcategories in 2003: general and biology, the latter of which has hosted 450 students. Since 2003, the MRSP-Bio program has been administered by Mandana Sassanfar, a biology lecturer in charge of the Department of Biology’s diversity and outreach programs. Since then, nearly 70 MSRP alumni have, like Booker, continued their research as graduate students at MIT.

Going for Gould

Bernard “Bernie” Gould ’32, who received his BS from MIT, was a longstanding and beloved biochemistry professor in the Department of Biology, well known for being an incredibly dedicated mentor to biology and pre-med students at MIT for nearly 40 years. His wife, Sophia Gould CMP ’48, shared his passion for counseling students. To honor this investment in encouraging student learning, the Goulds’ son, Michael, and his wife, Sara Moss, founded the Bernard S. and Sophia G. Gould Fund in 2016. Gould is a philanthropist and the retired chairman and CEO of Bloomingdales. Moss is the vice chairman of Estée Lauder Companies. The Gould Fellow Fund sponsors students, such as Elliott, in MSRP-Bio. Each year, Gould and Moss return to the MIT campus to meet with students benefitting from their support.

Recently, the couple has designated a second fund, which will aid in extending the academic careers of students interested in the life sciences by providing support for MSRP-Bio alumni entering into the MIT biology graduate program.

Six of the 16 Gould Fellowship alumni who have graduated from college have already been admitted to MIT as graduate students. “This is an exceptionally high rate by any standards, which demonstrates the amazing success of this initiative,” says Sassanfar. “Gould Fellows are truly grateful for the generosity of Mike and Sara and are very eager to succeed and give back to their communities,” a goal that is always stressed by the founders.

With successful role models from previous MSRP cohorts, like Booker, combined with philanthropy from those like Gould and Moss, who believe strongly in supporting the education of our next generation of scientists, students are given the opportunity to thrive.

Guided by AI, robotic platform automates molecule manufacture

by Becky Ham | MIT News correspondent |

Guided by artificial intelligence and powered by a robotic platform, a system developed by MIT researchers moves a step closer to automating the production of small molecules that could be used in medicine, solar energy, and polymer chemistry.

The system, described in the August 8 issue of Science, could free up bench chemists from a variety of routine and time-consuming tasks, and may suggest possibilities for how to make new molecular compounds, according to the study co-leaders Klavs F. Jensen, the Warren K. Lewis Professor of Chemical Engineering, and Timothy F. Jamison, the Robert R. Taylor Professor of Chemistry and associate provost at MIT.

The technology “has the promise to help people cut out all the tedious parts of molecule building,” including looking up potential reaction pathways and building the components of a molecular assembly line each time a new molecule is produced, says Jensen.

“And as a chemist, it may give you inspirations for new reactions that you hadn’t thought about before,” he adds.

Other MIT authors on the Science paper include Connor W. Coley, Dale A. Thomas III, Justin A. M. Lummiss, Jonathan N. Jaworski, Christopher P. Breen, Victor Schultz, Travis Hart, Joshua S. Fishman, Luke Rogers, Hanyu Gao, Robert W. Hicklin, Pieter P. Plehiers, Joshua Byington, John S. Piotti, William H. Green, and A. John Hart.

From inspiration to recipe to finished product

The new system combines three main steps. First, software guided by artificial intelligence suggests a route for synthesizing a molecule, then expert chemists review this route and refine it into a chemical “recipe,” and finally the recipe is sent to a robotic platform that automatically assembles the hardware and performs the reactions that build the molecule.

Coley and his colleagues have been working for more than three years to develop the open-source software suite that suggests and prioritizes possible synthesis routes. At the heart of the software are several neural network models, which the researchers trained on millions of previously published chemical reactions drawn from the Reaxys and U.S. Patent and Trademark Office databases. The software uses these data to identify the reaction transformations and conditions that it believes will be suitable for building a new compound.

“It helps makes high-level decisions about what kinds of intermediates and starting materials to use, and then slightly more detailed analyses about what conditions you might want to use and if those reactions are likely to be successful,” says Coley.

“One of the primary motivations behind the design of the software is that it doesn’t just give you suggestions for molecules we know about or reactions we know about,” he notes. “It can generalize to new molecules that have never been made.”

Chemists then review the suggested synthesis routes produced by the software to build a more complete recipe for the target molecule. The chemists sometimes need to perform lab experiments or tinker with reagent concentrations and reaction temperatures, among other changes.

“They take some of the inspiration from the AI and convert that into an executable recipe file, largely because the chemical literature at present does not have enough information to move directly from inspiration to execution on an automated system,” Jamison says.

The final recipe is then loaded on to a platform where a robotic arm assembles modular reactors, separators, and other processing units into a continuous flow path, connecting pumps and lines that bring in the molecular ingredients.

“You load the recipe — that’s what controls the robotic platform — you load the reagents on, and press go, and that allows you to generate the molecule of interest,” says Thomas. “And then when it’s completed, it flushes the system and you can load the next set of reagents and recipe, and allow it to run.”

Unlike the continuous flow system the researchers presented last year, which had to be manually configured after each synthesis, the new system is entirely configured by the robotic platform.

“This gives us the ability to sequence one molecule after another, as well as generate a library of molecules on the system, autonomously,” says Jensen.

The design for the platform, which is about two cubic meters in size — slightly smaller than a standard chemical fume hood — resembles a telephone switchboard and operator system that moves connections between the modules on the platform.

“The robotic arm is what allowed us to manipulate the fluidic paths, which reduced the number of process modules and fluidic complexity of the system, and by reducing the fluidic complexity we can increase the molecular complexity,” says Thomas. “That allowed us to add additional reaction steps and expand the set of reactions that could be completed on the system within a relatively small footprint.”

Toward full automation

The researchers tested the full system by creating 15 different medicinal small molecules of different synthesis complexity, with processes taking anywhere between two hours for the simplest creations to about 68 hours for manufacturing multiple compounds.

The team synthesized a variety of compounds: aspirin and the antibiotic secnidazole in back-to-back processes; the painkiller lidocaine and the antianxiety drug diazepam in back-to-back processes using a common feedstock of reagents; the blood thinner warfarin and the Parkinson’s disease drug safinamide, to show how the software could design compounds with similar molecular components but differing 3-D structures; and a family of five ACE inhibitor drugs and a family of four nonsteroidal anti-inflammatory drugs.

“I’m particularly proud of the diversity of the chemistry and the kinds of different chemical reactions,” says Jamison, who said the system handled about 30 different reactions compared to about 12 different reactions in the previous continuous flow system.

“We are really trying to close the gap between idea generation from these programs and what it takes to actually run a synthesis,” says Coley. “We hope that next-generation systems will increase further the fraction of time and effort that scientists can focus their efforts on creativity and design.”

The research was supported, in part, by the U.S. Defense Advanced Research Projects Agency (DARPA) Make-It program.

Characterizing tau aggregates in neurodegenerative diseases

by Danielle Randall Doughty | Department of Chemistry |

The microtubule-binding protein tau in neurons of the central nervous system can misfold into filamentous aggregates under certain conditions. These filaments are found in many neurodegenerative diseases such as Alzheimer’s disease, chronic traumatic encephalopathy (CTE), and progressive supranuclear palsy. Understanding the molecular structure and dynamics of tau fibrils is important for designing anti-tau inhibitors to combat these diseases.

Cryoelectron microscopy studies have recently shown that tau fibrils derived from postmortem brains of Alzheimer’s patients adopt disease-specific molecular conformations. These conformations consist of long sheets, known as beta sheets, that are formed by thousands of protein molecules aligned in parallel. In contrast, recombinant tau fibrillized using the anionic polymer heparin was reported to exhibit polymorphic structures. However, the origin of this in vitro structural polymorphism as compared to the in vivo structural homogeneity is unknown.

Using solid-state nuclear magnetic resonance (SSNMR) spectroscopy, MIT Professor Mei Hong, in collaboration with Professor Bill DeGrado at the University of California at San Francisco, has shown in a paper, published July 29 in PNAS, that the beta sheet core of heparin-fibrillized tau in fact adopts a single molecular conformation. The tau protein they studied contains four microtubule-binding repeats, and the beta sheet fibril core spans the second and third repeats.

Clarifying biochemical studies of tau and its fibril formation

Previous research on this subject had reported four polymorphic structures of four-repeat (4R) tau fibrils, a polymorphism that led many labs to believe that in vitro tau fibrils were poor mimics of the in vivo patient-brain tau. However, through the use of their SSNMR spectra, which show only a single set of peaks for the protein, Hong and DeGrado discovered a crucial biochemical problem that led to the previous polymorphism.

Once this error was corrected, 4R tau was found to display only a single molecular structure. The revelation of this common biochemical problem, which is protease contamination in the heparin used to fibrillize tau, will significantly clarify and positively impact the field of tau research.

Preventing the formation of tau aggregates in Alzheimer’s disease and beyond

The three-dimensional fold of this four-repeat tau fibril core is distinct from the fibril core of the Alzheimer’s disease tau, which consists of a mixture of three- and four-repeat isoforms. “The tau isoform we studied is the same as that in diseases such as progressive supranuclear palsy, [so] the structural model we determined suggests what the patient brain tau from PSP may look like. Knowing this structure will be important for designing anti-tau inhibitors to either disrupt fibrils or prevent fibrils from forming in the first place,” explains Hong.

This SSNMR study also reported detailed characterizations of the mobilities of amino acid residues outside the rigid beta sheet core. These residues, which appear as a “fuzzy coat” in transmission electron micrographs, exhibit increasingly larger-amplitude motion towards the two ends of the polypeptide chain. Interestingly, the first and fourth microtubule-binding repeats, although excluded from the rigid core, display local b-strand conformations and are semi-rigid.

These structural and dynamical results suggest future medicinal interventions to disrupt or prevent the formation of tau aggregates in some neurodegenerative diseases.

Four new faces in the School of Science faculty

by School of Science |

This fall, the School of Science will welcome four new members joining the faculty in the departments of Biology, Brain and Cognitive Sciences, and Chemistry.

Evelina Fedorenko investigates how our brains process language. She has developed novel analytic approaches for functional magnetic resonance imaging (fMRI) and other brain imaging techniques to help answer the questions of how the language processing network functions and how it relates to other networks in the brain. She works with both neurotypical individuals and individuals with brain disorders. Fedorenko joins the Department of Brain and Cognitive Sciences as an assistant professor. She received her BA from Harvard University in linguistics and psychology and then completed her doctoral studies at MIT in 2007. After graduating from MIT, Fedorenko worked as a postdoc and then as a research scientist at the McGovern Institute for Brain Research. In 2014, she joined the faculty at Massachusetts General Hospital and Harvard Medical School, where she was an associate researcher and an assistant professor, respectively. She is also a member of the McGovern Institute.

Morgan Sheng focuses on the structure, function, and turnover of synapses, the junctions that allow communication between brain cells. His discoveries have improved our understanding of the molecular basis of cognitive function and diseases of the nervous system, such as autism, Alzheimer’s disease, and dementia. Being both a physician and a scientist, he incorporates genetic as well as biological insights to aid the study and treatment of mental illnesses and neurodegenerative diseases. He rejoins the Department of Brain and Cognitive Sciences (BCS), returning as a professor of neuroscience, a position he also held from 2001 to 2008. At that time, he was a member of the Picower Institute for Learning and Memory, a joint appointee in the Department of Biology, and an investigator of the Howard Hughes Medical Institute. Sheng earned his PhD from Harvard University in 1990, completed a postdoc at the University of California at San Francisco in 1994, and finished his medical training with a residency in London in 1986. From 1994 to 2001, he researched molecular and cellular neuroscience at Massachusetts General Hospital and Harvard Medical School. From 2008 to 2019 he was vice president of neuroscience at Genentech, a leading biotech company. In addition to his faculty appointment in BCS, Sheng is core institute member and co-director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, as well as an affiliate member of the McGovern Institute and the Picower Institute.

Seychelle Vos studies genome organization and its effect on gene expression at the intersection of biochemistry and genetics. Vos uses X-ray crystallography, cryo-electron microscopy, and biophysical approaches to understand how transcription is physically coupled to the genome’s organization and structure. She joins the Department of Biology as an assistant professor after completing a postdoc at the Max Plank Institute for Biophysical Chemistry. Vos received her BS in genetics in 2008 from the University of Georgia and her PhD in molecular and cell biology in 2013 from the University of California at Berkeley.

Xiao Wang is a chemist and molecular engineer working to improve our understanding of biology and human health. She focuses on brain function and dysfunction, producing and applying new chemical, biophysical, and genomic tools at the molecular level. Previously, she focused on RNA modifications and how they impact cellular function. Wang is joining MIT as an assistant professor in the Department of Chemistry. She was previously a postdoc of the Life Science Research Foundation at Stanford University. Wang received her BS in chemistry and molecular engineering from Peking University in 2010 and her PhD in chemistry from the University of Chicago in 2015. She is also a core member of the Broad Institute of MIT and Harvard.

Seven MIT faculty win 2019 Presidential Early Career Awards

by Julia Keller | School of Science |

Seven MIT faculty members were among the more than 300 recipients of the 2019 Presidential Early Career Awards for Scientists and Engineers (PECASE), the highest honor bestowed by the U.S. government to science and engineering professionals in the early stages of their independent research careers.

Those from MIT who were honored were:

  • Joseph Checkelsky, assistant professor in the Department of Physics;
  • Kwanghun Chung, associate professor in the departments of Brain and Cognitive Sciences and Chemical Engineering
  • James M. LeBeau, the John Chipman Associate Professor of Materials Science and Engineering;
  • Yen-Jie Lee, the Class of 1958 Career Development Associate Professor in the Department of Physics;
  • Benedetto Marelli, the Paul M. Cook Career Development Assistant Professor in the Department of Civil and Environmental Engineering;
  • Tracy Slatyer, the Jerrold R. Zacharias Career Development Associate Professor of Physics; and
  • Yogesh Surendranath, the Paul M. Cook Career Development Assistant Professor in the Department of Chemistry.

All of the 2019 MIT recipients were employed or funded by the following U.S. departments and agencies: Department of Defense, Department of Energy, and the Department of Health and Human Services.

These departments and agencies annually nominate the most meritorious scientists and engineers whose early accomplishments show exceptional promise for leadership in science and engineering and contributing to the awarding agencies’ missions.

Established by President Bill Clinton in 1996, the PECASE awards are coordinated by the Office of Science and Technology Policy within the Executive Office of the President. Awardees are selected for their pursuit of innovative research at the frontiers of science and technology and their commitment to community service as demonstrated through scientific leadership, public education, or community outreach.

Meet the 2019 tenured professors in the School of Science

by Julia Keller | School of Science |

MIT granted tenure to eight School of Science faculty members in the departments of Biology; Chemistry; Earth, Atmospheric and Planetary Sciences; Mathematics; and Physics.

William Detmold’s research within the area of theoretical particle and nuclear physics incorporates analytical methods, as well as the power of the world’s largest supercomputers, to understand the structure, dynamics, and interactions of particles like protons and to look for evidence of new physical laws at the sub-femtometer scale probed in experiments such as those at the Large Hadron Collider. He joined the Department of Physics in 2012 from the College of William and Mary, where he was an assistant professor. Prior to that, he was a research assistant professor at the University of Washington. He received his BS and PhD from the University of Adelaide in Australia in 1996 and 2002, respectively. Detmold is a researcher in the Center for Theoretical Physics in the Laboratory for Nuclear Science.

Semyon Dyatlov explores scattering theory, quantum chaos, and general relativity by employing microlocal analytical and dynamical system methods. He came to the Department of Mathematics as a research fellow in 2013 and became an assistant professor in 2015. He completed his doctorate in mathematics at the University of California at Berkeley in 2013 after receiving a BS in mathematics at Novosibirsk State University in Russia in 2008. Dyatlov spent time after finishing his PhD as a postdoc at the Mathematical Sciences Research Institute before moving to MIT.

Mary Gehring studies plant epigenetics. By using a combination of genetic, genomic, and molecular biology, she explores how plants inherit and interpret information that is not encoded in their DNA to better understand plant growth and development. Her lab focuses primarily on Arabidopsis thaliana, a small flowering plant that is a model species for plant research. Gehring joined the Department of Biology in 2010 after performing postdoctoral research at the Fred Hutchinson Cancer Research Center. She received her BA in biology from Williams College in 1998 and her doctorate from the University of California at Berkeley in 2005. She is also a member of the Whitehead Institute for Biomedical Research.

David McGee performs research in the field of paleoclimate, merging information from stalagmites, lake deposits, and marine sediments with insights from models and theory to understand how precipitation patterns and atmospheric circulation varied in the past. He came to MIT in 2012, joining the Department of Earth, Atmospheric and Planetary Sciences after completing a NOAA Climate and Global Change Postdoctoral Fellowship at the University of Minnesota. Before that, he attended Carleton College for his BA in geology in 1993-97, Chatham College for an MA in teaching from 1999 to 2003, Tulane University for his MS from 2004 to 2006, and Columbia University for his PhD from 2006 to 2009. McGee is the director of the MIT Terrascope First-Year Learning Community, a role he has held for the past four years.

Ankur Moitra works at the interface between theoretical computer science and machine learning by developing algorithms with provable guarantees and foundations for reasoning about their behavior. He joined the Department of Mathematics in 2013. Prior to that, he received his BS in electrical and computer engineering from Cornell University in 2007, and his MS and PhD in computer science from MIT in 2009 and 2011, respectively. He was a National Science Foundation postdoc at the Institute for Advanced Study until 2013. Moitra was a 2018 recipient of a School of Science Teaching Prize. He is also a principal investigator in the Computer Science and Artificial Intelligence Laboratory (CSAIL) and a core member of the Center for Statistics.

Matthew Shoulders focuses on integrating biology and chemistry to understand how proteins function in the cellular setting, including proteins’ shape, quantity, and location within the body. This research area has important implications for genetic disorders and neurodegenerative diseases such as Alzheimer’s, diabetes, cancer, and viral infections. Shoulders’ lab works to elucidate, at the molecular level, how cells solve the protein-folding problem, and then uses that information to identify how diseases can develop and to provide insight into new targets for drug development. Shoulders joined the Department of Chemistry in 2012 after earning a BS in chemistry and minor in biochemistry from Virginia Tech in 2004 and a PhD in chemistry from the University of Wisconsin at Madison in 2009. He is also an associate member of the Broad Institute of MIT and Harvard, and a member of the MIT Center for Environmental Health Sciences.

Tracy Slatyer researches fundamental aspects of theoretical physics, answering questions about both visible and dark matter by searching for potential indications of new physics in astrophysical and cosmological data. She has developed and adapted novel techniques for data analysis, modeling, and calculations in quantum field theory; her work has also inspired a range of experimental investigations. The Department of Physics welcomed Slatyer in 2013 after she completed a three-year postdoctoral fellowship at the Institute for Advanced Study. She majored in theoretical physics as an undergraduate at the Australian National University, receiving a BS in 2005, and completed her PhD in physics at Harvard University in 2010. In 2017, Slatyer received the School of Science Prize in Graduate Teaching and was also named the first recipient of the school’s Future of Science Award. She is a member of the Center for Theoretical Physics in the Laboratory for Nuclear Science.

Michael Williams uses novel experimental methods to improve our knowledge of fundamental particles, including searching for new particles and forces, such as dark matter. He also works on advancing the usage of machine learning within the domain of particle physics research. He joined the Department of Physics in 2012. He previously attended Saint Vincent College as an undergraduate, where he double majored in mathematics and physics. Graduating in 2001, Williams then pursued a doctorate at Carnegie Mellon University, which he completed in 2007. From 2008 to 2012 he was a postdoc at Imperial College London. He is a member of the Laboratory for Nuclear Science.

Experiments show dramatic increase in solar cell output

by David L. Chandler | MIT News Office |

In any conventional silicon-based solar cell, there is an absolute limit on overall efficiency, based partly on the fact that each photon of light can only knock loose a single electron, even if that photon carried twice the energy needed to do so. But now, researchers have demonstrated a method for getting high-energy photons striking silicon to kick out two electrons instead of one, opening the door for a new kind of solar cell with greater efficiency than was thought possible.

While conventional silicon cells have an absolute theoretical maximum efficiency of about 29.1 percent conversion of solar energy, the new approach, developed over the last several years by researchers at MIT and elsewhere, could bust through that limit, potentially adding several percentage points to that maximum output. The results are described today in the journal Nature, in a paper by graduate student Markus Einzinger, professor of chemistry Moungi Bawendi, professor of electrical engineering and computer science Marc Baldo, and eight others at MIT and at Princeton University.

The basic concept behind this new technology has been known for decades, and the first demonstration that the principle could work was carried out by some members of this team six years ago. But actually translating the method into a full, operational silicon solar cell took years of hard work, Baldo says.

That initial demonstration “was a good test platform” to show that the idea could work, explains Daniel Congreve PhD ’15, an alumnus now at the Rowland Institute at Harvard, who was the lead author in that prior report and is a co-author of the new paper. Now, with the new results, “we’ve done what we set out to do” in that project, he says.

The original study demonstrated the production of two electrons from one photon, but it did so in an organic photovoltaic cell, which is less efficient than a silicon solar cell. It turned out that transferring the two electrons from a top collecting layer made of tetracene into the silicon cell “was not straightforward,” Baldo says. Troy Van Voorhis, a professor of chemistry at MIT who was part of that original team, points out that the concept was first proposed back in the 1970s, and says wryly that turning that idea into a practical device “only took 40 years.”

The key to splitting the energy of one photon into two electrons lies in a class of materials that possess “excited states” called excitons, Baldo says: In these excitonic materials, “these packets of energy propagate around like the electrons in a circuit,” but with quite different properties than electrons. “You can use them to change energy — you can cut them in half, you can combine them.” In this case, they were going through a process called singlet exciton fission, which is how the light’s energy gets split into two separate, independently moving packets of energy. The material first absorbs a photon, forming an exciton that rapidly undergoes fission into two excited states, each with half the energy of the original state.

But the tricky part was then coupling that energy over into the silicon, a material that is not excitonic. This coupling had never been accomplished before.

As an intermediate step, the team tried coupling the energy from the excitonic layer into a material called quantum dots. “They’re still excitonic, but they’re inorganic,” Baldo says. “That worked; it worked like a charm,” he says. By understanding the mechanism taking place in that material, he says, “we had no reason to think that silicon wouldn’t work.”

What that work showed, Van Voorhis says, is that the key to these energy transfers lies in the very surface of the material, not in its bulk. “So it was clear that the surface chemistry on silicon was going to be important. That was what was going to determine what kinds of surface states there were.” That focus on the surface chemistry may have been what allowed this team to succeed where others had not, he suggests.

The key was in a thin intermediate layer. “It turns out this tiny, tiny strip of material at the interface between these two systems [the silicon solar cell and the tetracene layer with its excitonic properties] ended up defining everything. It’s why other researchers couldn’t get this process to work, and why we finally did.” It was Einzinger “who finally cracked that nut,” he says, by using a layer of a material called hafnium oxynitride.

The layer is only a few atoms thick, or just 8 angstroms (ten-billionths of a meter), but it acted as a “nice bridge” for the excited states, Baldo says. That finally made it possible for the single high-energy photons to trigger the release of two electrons inside the silicon cell. That produces a doubling of the amount of energy produced by a given amount of sunlight in the blue and green part of the spectrum. Overall, that could produce an increase in the power produced by the solar cell — from a theoretical maximum of 29.1 percent, up to a maximum of about 35 percent.

Actual silicon cells are not yet at their maximum, and neither is the new material, so more development needs to be done, but the crucial step of coupling the two materials efficiently has now been proven. “We still need to optimize the silicon cells for this process,” Baldo says. For one thing, with the new system those cells can be thinner than current versions. Work also needs to be done on stabilizing the materials for durability. Overall, commercial applications are probably still a few years off, the team says.

Other approaches to improving the efficiency of solar cells tend to involve adding another kind of cell, such as a perovskite layer, over the silicon. Baldo says “they’re building one cell on top of another. Fundamentally, we’re making one cell — we’re kind of turbocharging the silicon cell. We’re adding more current into the silicon, as opposed to making two cells.”

The researchers have measured one special property of hafnium oxynitride that helps it transfer the excitonic energy. “We know that hafnium oxynitride generates additional charge at the interface, which reduces losses by a process called electric field passivation. If we can establish better control over this phenomenon, efficiencies may climb even higher.” Einzinger says. So far, no other material they’ve tested can match its properties.

The research was supported as part of the MIT Center for Excitonics, funded by the U.S. Department of Energy.

For Catherine Drennan, teaching and research are complementary passions

by Leda Zimmerman | MIT Energy Initiative |

Catherine Drennan says nothing in her job thrills her more than the process of discovery. But Drennan, a professor of biology and chemistry, is not referring to her landmark research on protein structures that could play a major role in reducing the world’s waste carbons.

“Really the most exciting thing for me is watching my students ask good questions, problem-solve, and then do something spectacular with what they’ve learned,” she says.

For Drennan, research and teaching are complementary passions, both flowing from a deep sense of “moral responsibility.” Everyone, she says, “should do something, based on their skill set, to make some kind of contribution.”

Drennan’s own research portfolio attests to this sense of mission. Since her arrival at MIT 20 years ago, she has focused on characterizing and harnessing metal-containing enzymes that catalyze complex chemical reactions, including those that break down carbon compounds.

She got her start in the field as a graduate student at the University of Michigan, where she became captivated by vitamin B12. This very large vitamin contains cobalt and is vital for amino acid metabolism, the proper formation of the spinal cord, and prevention of certain kinds of anemia. Bound to proteins in food, B12 is released during digestion.

“Back then, people were suggesting how B12-dependent enzymatic reactions worked, and I wondered how they could be right if they didn’t know what B12-dependent enzymes looked like,” she recalls. “I realized I needed to figure out how B12 is bound to protein to really understand what was going on.”

Drennan seized on X-ray crystallography as a way to visualize molecular structures. Using this technique, which involves bouncing X-ray beams off a crystallized sample of a protein of interest, she figured out how vitamin B12 is bound to a protein molecule.

“No one had previously been successful using this method to obtain a B12-bound protein structure, which turned out to be gorgeous, with a protein fold surrounding a novel configuration of the cofactor,” says Drennan.

Carbon-loving microbes show the way 

These studies of B12 led directly to Drennan’s one-carbon work. “Metallocofactors such as B12 are important not just medically, but in environmental processes,” she says. “Many microbes that live on carbon monoxide, carbon dioxide, or methane — eating carbon waste or transforming carbon — use metal-containing enzymes in their metabolic pathways, and it seemed like a natural extension to investigate them.”

Some of Drennan’s earliest work in this area, dating from the early 2000s, revealed a cluster of iron, nickel, and sulfur atoms at the center of the enzyme carbon monoxide dehydrogenase (CODH). This so-called C-cluster serves hungry microbes, allowing them to “eat” carbon monoxide and carbon dioxide.

Recent experiments by Drennan analyzing the structure of the C-cluster-containing enzyme CODH showed that in response to oxygen, it can change configurations, with sulfur, iron, and nickel atoms cartwheeling into different positions. Scientists looking for new avenues to reduce greenhouse gases took note of this discovery. CODH, suggested Drennan, might prove an effective tool for converting waste carbon dioxide into a less environmentally destructive compound, such as acetate, which might also be used for industrial purposes.

Drennan has also been investigating the biochemical pathways by which microbes break down hydrocarbon byproducts of crude oil production, such as toluene, an environmental pollutant.

“It’s really hard chemistry, but we’d like to put together a family of enzymes to work on all kinds of hydrocarbons, which would give us a lot of potential for cleaning up a range of oil spills,” she says.

The threat of climate change has increasingly galvanized Drennan’s research, propelling her toward new targets. A 2017 study she co-authored in Science detailed a previously unknown enzyme pathway in ocean microbes that leads to the production of methane, a formidable greenhouse gas: “I’m worried the ocean will make a lot more methane as the world warms,” she says.

Drennan hopes her work may soon help to reduce the planet’s greenhouse gas burden. Commercial firms have begun using the enzyme pathways that she studies, in one instance employing a proprietary microbe to capture carbon dioxide produced during steel production — before it is released into the atmosphere — and convert it into ethanol.

“Reengineering microbes so that enzymes take not just a little, but a lot of carbon dioxide out of the environment — this is an area I’m very excited about,” says Drennan.

Creating a meaningful life in the sciences 

At MIT, she has found an increasingly warm welcome for her efforts to address the climate challenge.

“There’s been a shift in the past decade or so, with more students focused on research that allows us to fuel the planet without destroying it,” she says.

In Drennan’s lab, a postdoc, Mary Andorfer, and a rising junior, Phoebe Li, are currently working to inhibit an enzyme present in an oil-consuming microbe whose unfortunate residence in refinery pipes leads to erosion and spills. “They are really excited about this research from the environmental perspective and even made a video about their microorganism,” says Drennan.

Drennan delights in this kind of enthusiasm for science. In high school, she thought chemistry was dry and dull, with no relevance to real-world problems. It wasn’t until college that she “saw chemistry as cool.”

The deeper she delved into the properties and processes of biological organisms, the more possibilities she found. X-ray crystallography offered a perfect platform for exploration. “Oh, what fun to tell the story about a three-dimensional structure — why it is interesting, what it does based on its form,” says Drennan.

The elements that excite Drennan about research in structural biology — capturing stunning images, discerning connections among biological systems, and telling stories — come into play in her teaching. In 2006, she received a $1 million grant from the Howard Hughes Medical Institute (HHMI) for her educational initiatives that use inventive visual tools to engage undergraduates in chemistry and biology. She is both an HHMI investigator and an HHMI professor, recognition of her parallel accomplishments in research and teaching, as well as a 2015 MacVicar Faculty Fellow for her sustained contribution to the education of undergraduates at MIT.

Drennan attempts to reach MIT students early. She taught introductory chemistry classes from 1999 to 2014, and in fall 2018 taught her first introductory biology class.

“I see a lot of undergraduates majoring in computer science, and I want to convince them of the value of these disciplines,” she says. “I tell them they will need chemistry and biology fundamentals to solve important problems someday.”

Drennan happily migrates among many disciplines, learning as she goes. It’s a lesson she hopes her students will absorb. “I want them to visualize the world of science and show what they can do,” she says. “Research takes you in different directions, and we need to bring the way we teach more in line with our research.”

She has high expectations for her students. “They’ll go out in the world as great teachers and researchers,” Drennan says. “But it’s most important that they be good human beings, taking care of other people, asking what they can do to make the world a better place.”

This article appears in the Spring 2019 issue of Energy Futures, the magazine of the MIT Energy Initiative.