Author: MIT News

Chemists gain new insights into the behavior of water in an influenza virus channel

by Danielle Doughty | Department of Chemistry |

In a new study of water dynamics, a team of MIT chemists led by Professor Mei Hong, in collaboration with Associate Professor Adam Willard, has discovered that water in an ion channel is anisotropic, or partially aligned. The researchers’ data, the first of their kind, prove the relation of water dynamics and order to the conduction of protons in an ion channel. The work also provides potential new avenues for the development of antiviral drugs or other treatments.

Members of the Hong lab conducted sophisticated nuclear magnetic resonance (NMR) experiments to prove the existence of anisotropic water in the proton channel of the influenza M virus, while members of the Willard group carried out independent all-atom molecular dynamics simulations to validate and augment the experimental data. Their study, of which Hong was the senior author, was published in Communications Biology, and was co-authored by Martin Gelenter, Venkata Mandala, and Aurelio Dregni of the Hong Lab, and Michiel Niesen and Dina Sharon of the Willard group.

Channel water and influenza virus

The influenza B virus protein BM2 is a protein channel that acidifies the virus, helping it to release its genetic material into infected cells. The water in this channel plays a critical role in helping the influenza virus become infectious, because it facilitates proton conduction inside the channel to cross the lipid membrane.

Previously, Hong’s lab studied how the amino acid histidine shuttles protons from water into the flu virus, but they hadn’t investigated the water molecules themselves in detail. This new study has provided the missing link in a full understanding of the mixed hydrogen-bonded chain between water and histidine inside the M2 channel. To curb the flu virus protein, the channel would have to be plugged with small molecules — i.e., antiviral drugs — so that the water pathway would be broken.

In order to align the water-water hydrogen bonds for “proton hopping,” water molecules must be at least partially oriented. However, to experimentally detect the tiny amount of residual alignment of water molecules in a channel, without freezing the sample, is extremely difficult. As a result, the majority of previous studies on the topic were conducted by computational chemists like Willard. Experimental data on this topic were typically restricted to crystal structures obtained at cryogenic temperatures. The Hong lab adopted a relaxation NMR technique that can be employed at the much balmier temperature of around 0 degrees Celsius. At this temperature, the water molecules rotated just slowly enough for the researchers to observe the mobility and residual orientation in the channel for the first time.

More space, more order

The evidence yielded by Hong’s NMR experiments indicated that the water molecules in the open state of the BM2 channel are more aligned than they are in the closed state, even though there are many more water molecules in the open state. The researchers detected this residual order by measuring a magnetic property called chemical shift anisotropy for the water protons. The higher water alignment at low pH came as a surprise.

“This was initially counterintuitive to us,” says Hong. “We know from a lot of previous NMR data that the open channel has more water molecules, so one would think that these water molecules should be more disordered and random in the wider channel. But no, the waters are actually slightly better aligned based on the relaxation NMR data.” Molecular dynamic simulations indicated that this order is induced by the key proton-selective residue, a histidine, which is positively charged at low pH.

By employing solid-state NMR spectroscopy and molecular dynamics simulations, the researchers also found that water rotated and translated across the channel more rapidly in the low-pH open state than in the high-pH closed state. These results together indicate that the water molecules undergo small-amplitude reorientations to establish the alignment that is necessary for proton hopping.

Inhibiting proton conduction, blocking the virus

By using molecular dynamics simulations performed by Willard and his group, the researchers were able to observe that the water network has fewer hydrogen-bonding bottlenecks in the open state than in the closed state. Thus, faster dynamics and higher orientational order of water molecules in the open channel establish the water network structure that is necessary for proton hopping and successful infection on the virus’ part.

When a flu virus enters a cell, it goes into a small compartment called the endosome. The endosome compartment is acidic, which triggers the protein to open its water-permeated pathway and conduct the protons into the virus. Acidic pH has a high concentration of hydrogen ions, which is what the M2 protein conducts. Without the water molecules relaying the protons, the protons will not reach the histidine, a critical amino acid residue. The histidine is the proton-selective residue, and it rotates in order to shuttle the protons carried by the water molecules. The relay chain between the water molecules and the histidine is therefore responsible for proton conduction through the M2 channel. Therefore, the findings indicated in this research could prove relevant to the development of antiviral drugs and other practical applications.

Found in space: Complex carbon-based molecules

by Anne Trafton | MIT News Office |

Much of the carbon in space is believed to exist in the form of large molecules called polycyclic aromatic hydrocarbons (PAHs). Since the 1980s, circumstantial evidence has indicated that these molecules are abundant in space, but they have not been directly observed.

Now, a team of researchers led by MIT Assistant Professor Brett McGuire has identified two distinctive PAHs in a patch of space called the Taurus Molecular Cloud (TMC-1). PAHs were believed to form efficiently only at high temperatures — on Earth, they occur as byproducts of burning fossil fuels, and they’re also found in char marks on grilled food. But the interstellar cloud where the research team observed them has not yet started forming stars, and the temperature is about 10 degrees above absolute zero.

This discovery suggests that these molecules can form at much lower temperatures than expected, and it may lead scientists to rethink their assumptions about the role of PAH chemistry in the formation of stars and planets, the researchers say.

“What makes the detection so important is that not only have we confirmed a hypothesis that has been 30 years in the making, but now we can look at all of the other molecules in this one source and ask how they are reacting to form the PAHs we’re seeing, how the PAHs we’re seeing may react with other things to possibly form larger molecules, and what implications that may have for our understanding of the role of very large carbon molecules in forming planets and stars,” says McGuire, who is a senior author of the new study.

Michael McCarthy, associate director of the Harvard-Smithsonian Center for Astrophysics, is another senior author of the study, which appears today in Science. The research team also includes scientists from several other institutions, including the University of Virginia, the National Radio Astronomy Observatory, and NASA’s Goddard Space Flight Center.

Distinctive signals

Starting in the 1980s, astronomers have used telescopes to detect infrared signals that suggested the presence of aromatic molecules, which are molecules that typically include one or more carbon rings. About 10 to 25 percent of the carbon in space is believed to be found in PAHs, which contain at least two carbon rings, but the infrared signals weren’t distinct enough to identify specific molecules.

“That means that we can’t dig into the detailed chemical mechanisms for how these are formed, how they react with one another or other molecules, how they’re destroyed, and the whole cycle of carbon throughout the process of forming stars and planets and eventually life,” McGuire says.

Although radio astronomy has been a workhorse of molecular discovery in space since the 1960s, radio telescopes powerful enough to detect these large molecules have only been around for a little over a decade. These telescopes can pick up molecules’ rotational spectra, which are distinctive patterns of light that molecules give off as they tumble through space. Researchers can then try to match patterns observed in space with patterns that they have seen from those same molecules in laboratories on Earth.

“Once you have that pattern match, you know there is no other molecule in existence that could be giving off that exact spectrum. And, the intensity of the lines and the relative strength of the different pieces of the pattern tells you something about how much of the molecule there is, and how warm or cold the molecule is,” McGuire says.

McGuire and his colleagues have been studying TMC-1 for several years because previous observations have revealed it to be rich in complex carbon molecules. A few years ago, one member of the research team observed hints that the cloud contain benzonitrile — a six-carbon ring attached to a nitrile (carbon-nitrogen) group.

The researchers then used the Green Bank Telescope, the world’s largest steerable radio telescope, to confirm the presence of benzonitrile. In their data, they also found signatures of two other molecules — the PAHs reported in this study. Those molecules, called 1-cyanonaphthalene and 2-cyanonaphthalene, consist of two benzene rings fused together, with a nitrile group attached to one ring.

“Detecting these molecules is a major leap forward in astrochemistry. We are beginning to connect the dots between small molecules — like benzonitrile — that have been known to exist in space, to the monolithic PAHs that are so important in astrophysics,” says Kelvin Lee, an MIT postdoc who is one of the authors of the study.

Finding these molecules in the cold, starless TMC-1 suggests that PAHs are not just the byproducts of dying stars, but may be assembled from smaller molecules.

“In the place where we found them, there is no star, so either they’re being built up in place or they are the leftovers of a dead star,” McGuire says. “We think that it’s probably a combination of the two — the evidence suggests that it is neither one pathway nor the other exclusively. That’s new and interesting because there really hadn’t been any observational evidence for this bottom-up pathway before.”

Carbon chemistry

Carbon plays a critical role in the formation of planets, so the suggestion that PAHs might be present even in starless, cold regions of space, may prompt scientists to rethink their theories of what chemicals are available during planet formation, McGuire says. As PAHs react with other molecules, they may start to form interstellar dust grains, which are the seeds of asteroids and planets.

“We need to entirely rethink our models of how the chemistry is evolving, starting from these starless cores, to include the fact that they are forming these large aromatic molecules,” he says.

McGuire and his colleagues now plan to further investigate how these PAHs formed, and what kinds of reactions they may undergo in space. They also plan to continue scanning TMC-1 with the powerful Green Bank Telescope. Once they have those observations from the interstellar cloud, the researchers can try to match up the signatures they find with data that they generate on Earth by putting two molecules into a reactor and blasting them with kilovolts of electricity, breaking them into bits and letting them recombine. This could result in hundreds of different molecules, many of which have never been seen on Earth.

“We need to continue to see what molecules are present in this interstellar source, because the more we know about the inventory, the more we can start trying to connect the pieces of this reaction web,” McGuire says.

The research was funded by NASA, the Smithsonian Institute, the National Science Foundation, the Alexander von Humboldt Foundation, and the European Union’s Horizon 2020 research and innovation program.

Faster drug discovery through machine learning

by Daniel Ackerman | MIT News Office |

Drugs can only work if they stick to their target proteins in the body. Assessing that stickiness is a key hurdle in the drug discovery and screening process. New research combining chemistry and machine learning could lower that hurdle.

The new technique, dubbed DeepBAR, quickly calculates the binding affinities between drug candidates and their targets. The approach yields precise calculations in a fraction of the time compared to previous state-of-the-art methods. The researchers say DeepBAR could one day quicken the pace of drug discovery and protein engineering.

“Our method is orders of magnitude faster than before, meaning we can have drug discovery that is both efficient and reliable,” says Bin Zhang, the Pfizer-Laubach Career Development Professor in Chemistry at MIT, an associate member of the Broad Institute of MIT and Harvard, and a co-author of a new paper describing the technique.

The research appears today in the Journal of Physical Chemistry Letters. The study’s lead author is Xinqiang Ding, a postdoc in MIT’s Department of Chemistry.

The affinity between a drug molecule and a target protein is measured by a quantity called the binding free energy — the smaller the number, the stickier the bind. “A lower binding free energy means the drug can better compete against other molecules,” says Zhang, “meaning it can more effectively disrupt the protein’s normal function.” Calculating the binding free energy of a drug candidate provides an indicator of a drug’s potential effectiveness. But it’s a difficult quantity to nail down.

Methods for computing binding free energy fall into two broad categories, each with its own drawbacks. One category calculates the quantity exactly, eating up significant time and computer resources. The second category is less computationally expensive, but it yields only an approximation of the binding free energy. Zhang and Ding devised an approach to get the best of both worlds.

Exact and efficient

DeepBAR computes binding free energy exactly, but it requires just a fraction of the calculations demanded by previous methods. The new technique combines traditional chemistry calculations with recent advances in machine learning.

The “BAR” in DeepBAR stands for “Bennett acceptance ratio,” a decades-old algorithm used in exact calculations of binding free energy. Using the Bennet acceptance ratio typically requires a knowledge of two “endpoint” states (e.g., a drug molecule bound to a protein and a drug molecule completely dissociated from a protein), plus knowledge of many intermediate states (e.g., varying levels of partial binding), all of which bog down calculation speed.

DeepBAR slashes those in-between states by deploying the Bennett acceptance ratio in machine-learning frameworks called deep generative models. “These models create a reference state for each endpoint, the bound state and the unbound state,” says Zhang. These two reference states are similar enough that the Bennett acceptance ratio can be used directly, without all the costly intermediate steps.

In using deep generative models, the researchers were borrowing from the field of computer vision. “It’s basically the same model that people use to do computer image synthensis,” says Zhang. “We’re sort of treating each molecular structure as an image, which the model can learn. So, this project is building on the effort of the machine learning community.”

While adapting a computer vision approach to chemistry was DeepBAR’s key innovation, the crossover also raised some challenges. “These models were originally developed for 2D images,” says Ding. “But here we have proteins and molecules — it’s really a 3D structure. So, adapting those methods in our case was the biggest technical challenge we had to overcome.”

A faster future for drug screening

In tests using small protein-like molecules, DeepBAR calculated binding free energy nearly 50 times faster than previous methods. Zhang says that efficiency means “we can really start to think about using this to do drug screening, in particular in the context of Covid. DeepBAR has the exact same accuracy as the gold standard, but it’s much faster.” The researchers add that, in addition to drug screening, DeepBAR could aid protein design and engineering, since the method could be used to model interactions between multiple proteins.

DeepBAR is “a really nice computational work” with a few hurdles to clear before it can be used in real-world drug discovery, says Michael Gilson, a professor of pharmaceutical sciences at the University of California at San Diego, who was not involved in the research. He says DeepBAR would need to be validated against complex experimental data. “That will certainly pose added challenges, and it may require adding in further approximations.”

In the future, the researchers plan to improve DeepBAR’s ability to run calculations for large proteins, a task made feasible by recent advances in computer science. “This research is an example of combining traditional computational chemistry methods, developed over decades, with the latest developments in machine learning,” says Ding. “So, we achieved something that would have been impossible before now.”

This research was funded, in part, by the National Institutes of Health.

Women in Innovation and STEM Database at MIT announces fellowship program

by David Sweeney | MIT Innovation Initiative |

WISDM, the Women in Innovation and STEM Database at MIT, celebrated the first anniversary of its digital launch on March 8 — International Women’s Day. To mark the occasion, the tremendous growth of the WISDM community, MIT Innovation Initiative (MITii), which manages the platform/community, announced the WISDM Fellowship Program.

WISDM promotes the visibility of women in the MIT academic community, increases gender diversity in innovation and entrepreneurship, and makes it easier to find talented and diverse speakers for various events. In partnership with MITii, WISDM founder Ritu Raman, an MIT postdoc and AAAS IF/THEN Ambassador, applied for and was awarded a $10,000 AAAS IF/THEN Ambassadors Grant for public engagement with science activities that teach, inspire, and promote the next generation of women in STEM. With this funding, WISDM launched a fellowship program for scientists interested in improving their public speaking capabilities.

“When I had the opportunity to apply for the grant, I immediately thought of WISDM as a great community of women who could benefit from professional development resources supported by this funding,” states Raman. “We all know from experience that the most impactful role models are often highly effective communicators. The WISDM Fellowship Program will help women leverage their scientific expertise by combining it with a formalized speaker training program with The Story Collider, and will also financially reward women for speaking engagements via honorariums. This new program is important to me because it reiterates the core philosophy of WISDM: Women’s expertise and time are valuable assets, and we need to make diverse voices a part of every conversation in STEM.”

Through the WISDM Fellows application and review process, 20 exceptional women were selected to participate in the program. They are:

  • Taylor Cannon, Department of Electrical Engineering and Computer Science
  • Cecile Chazot, Department of Materials Science and Engineering
  • Mara Freilich, MIT-Woods Hole Oceanography/Applied Ocean Science and Engineering
  • Stephanie Gaglione, Department of Chemical Engineering
  • Miela Gross, Department of Electrical Engineering and Computer Science
  • Ayse Guvenilir, Media Lab
  • Fatima Husain, Department of Earth, Atmospheric and Planetary Sciences
  • Eugenia Inda, Department of Electrical Engineering and Computer Science
  • Jessica Ingabire, Institute for Data, Systems, and Society
  • Lakshmi Amrutha Killada, Department of Mechanical Engineering
  • Zanele Munyikwa, MIT Sloan School of Management
  • Ufuoma Ovienmhada, Media Lab
  • Cadence Payne, Department of Aeronautics and Astronautics
  • Krista Pullen, Department of Biological Engineering
  • Julie Rorrer, Department of Chemical Engineering
  • Erica Salazar, Department of Nuclear Science and Engineering
  • Stephanie Smelyansky, Department of Chemistry
  • Kayla Storme, Department of Chemistry
  • Abigail Taussig, Department of Chemical Engineering
  • Jacqueline Valeri, Department of Biological Engineering

“In my family, storytelling has always been important,” says WISDM Fellow and Department of Nuclear Science and Engineering graduate student Erica Salazar. “Every holiday season, my family gathers at our annual tamalada (where we make tamales) to tell stories. It has the powerful ability to bring us closer together when we are apart most of the year. Storytelling is another medium to engage an audience to absorb abstract or difficult concepts in a personal way. I am honored, through this fellowship, to learn how to harness storytelling methods to create a personal bond with others — and particularly, to engage young girls and kids in STEM.”

Since its digital launch last March, the community has grown to 135 members, and the platform has received over 16,000 page views from more than 9,000 unique users in 83 countries. Current MIT graduate students, postdocs, technical associates, or research staff members who identify as a woman are eligible to join.

QS World University Rankings rates MIT No. 1 in 12 subjects, including Chemistry, for 2021

by MIT News Office |

MIT has been honored with 12 No. 1 subject rankings in the QS World University Rankings for 2021.

The Institute received a No. 1 ranking in the following QS subject areas: Architecture/Built Environment; 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.

Quacquarelli Symonds Limited subject rankings, published annually, are designed to help prospective students find the leading schools in their field of interest. Rankings are based on research quality and accomplishments, academic reputation, and graduate employment.

MIT has been ranked as the No. 1 university in the world by QS World University Rankings for nine straight years.

Chemists boost boron’s utility

by Anne Trafton | MIT News Office |

Boron, a metalloid element that sits next to carbon in the periodic table, has many traits that make it potentially useful as a drug component. Nonetheless, only five FDA-approved drugs contain boron, largely because molecules that contain boron are unstable in the presence of molecular oxygen.

MIT chemists have now designed a boron-containing chemical group that is 10,000 times more stable than its predecessors. This could make it possible to incorporate boron into drugs and potentially improve the drugs’ ability to bind their targets, the researchers say.

“It’s an entity that medicinal chemists can add to compounds they’re interested in, to provide desirable attributes that no other molecule will have,” says Ron Raines, the Firmenich Professor of Chemistry at MIT and the senior author of the new study.

To demonstrate the potential of this approach, Raines and his colleagues showed that they could improve the protein-binding strength of a drug that is used to treat diseases caused by the misfolding of a protein called transthyretin.

MIT graduate student Brian Graham and former graduate student Ian Windsor are the lead author of the study, which appears this week in the Proceedings of the National Academy of Sciences. Former MIT postdoc Brian Gold is also an author of the paper.

Hungry for electrons

Boron is most commonly found in the Earth’s crust in the form of minerals such as borax. It contains one fewer electron than carbon and is hungry for additional electrons. When boron is incorporated into a potential drug compound, that hunger for electrons often leads it to interact with an oxygen molecule (O2) or another reactive form of oxygen, which can destroy the compound.

The boron-containing drug bortezomib, which prevents cells from being able to break down used proteins, is an effective cancer chemotherapy agent. However, the drug is unstable and is destroyed readily by oxygen.

Previous research has shown that the stability of boron-containing compounds can be increased by appending benzene, a six-carbon ring. In 2018, Raines and his colleagues used this approach to create a modified version of a drug called darunavir, a protease inhibitor used to treat HIV/AIDS. They found that this molecule bound to HIV protease much more tightly than the original version of darunavir. However, later studies revealed that the molecule still did not survive for long under physiological conditions.

In the new paper, the researchers decided to use a chemical group called a carboxylate to further anchor boron within a molecule. An oxygen atom in the carboxylate forms a strong covalent bond — a type of bond that involves sharing pairs of electrons between atoms — with boron.

“That covalent bond pacifies the boron,” Raines says. “The boron can no longer react with an oxygen molecule in the way that boron in other contexts can, and it still retains its desirable properties.”

One of those desirable properties is the ability to form reversible covalent bonds with the target of the drug. This reversibility could prevent drugs from permanently locking onto incorrect targets, Raines says. Another useful feature is that the boron-containing group — also known as benzoxaboralone — forms many weaker bonds called hydrogen bonds with other molecules, which helps to ensure a tight fit once the right target is located.

Greater stability

Once they showed that benzoxaboralone was significantly more stable than boron in other contexts, the researchers used it to create a molecule that can bind to transthyretin. This protein, which carries hormones through the bloodstream, can cause amyloid diseases when it misfolds and clumps. Drugs that bind to transthyretin can stabilize it and prevent it from clumping. The research team showed that adding benzoxaboralone to an existing drug helped it to bind strongly with transthyretin.

Benzoxaboralone may offer medicinal chemists a useful tool that they can explore in many different types of drugs that bind to proteins or sugar molecules, Raines says. His lab is now working on a new version of darunavir that incorporates benzoxaboralone. They recently developed a way to synthesize this compound and are now in the process of measuring how strongly it binds to HIV protease.

“We are working hard on this because we think that this scaffold will provide much greater stability and utility than any other presentation of boron in a biological context,” Raines says.

MIT has filed for a patent on the use of benzoxaboralone in medicinal chemistry and other areas. The research was funded by the National Institutes of Health and the National Science Foundation.

Researchers improve efficiency of next-generation solar cell material

by David L. Chandler | MIT News |

Perovskites are a leading candidate for eventually replacing silicon as the material of choice for solar panels. They offer the potential for low-cost, low-temperature manufacturing of ultrathin, lightweight flexible cells, but so far their efficiency at converting sunlight to electricity has lagged behind that of silicon and some other alternatives.

Now, a new approach to the design of perovskite cells has pushed the material to match or exceed the efficiency of today’s typical silicon cell, which generally ranges from 20 to 22 percent, laying the groundwork for further improvements.

By adding a specially treated conductive layer of tin dioxide bonded to the perovskite material, which provides an improved path for the charge carriers in the cell, and by modifying the perovskite formula, researchers have boosted its overall efficiency as a solar cell to 25.2 percent — a near-record for such materials, which eclipses the efficiency of many existing solar panels. (Perovskites still lag significantly in longevity compared to silicon, however, a challenge being worked on by teams around the world.)

The findings are described in a paper in the journal Nature by recent MIT graduate Jason Yoo PhD ’20, professor of chemistry and Lester Wolfe Professor Moungi Bawendi, professor of electrical engineering and computer science and Fariborz Maseeh Professor in Emerging Technology Vladimir Bulović, and 11 others at MIT, in South Korea, and in Georgia.

Perovskites are a broad class of materials defined by the fact that they have a particular kind of molecular arrangement, or lattice, that resembles that of the naturally occurring mineral perovskite. There are vast numbers of possible chemical combinations that can make perovskites, and Yoo explains that these materials have attracted worldwide interest because “at least on paper, they could be made much more cheaply than silicon or gallium arsenide,” one of the other leading contenders. That’s partly because of the much simpler processing and manufacturing processes, which for silicon or gallium arsenide requires sustained heat of over 1,000 degrees Celsius. In contrast, perovskites can be processed at less than 200 C, either in solution or by vapor deposition.

The other major advantage of perovskite over silicon or many other candidate replacements is that it forms extremely thin layers while still efficiently capturing solar energy. “Perovskite cells have the potential to be lightweight compared to silicon, by orders of magnitude,” Bawendi says.

Perovskites have a higher bandgap than silicon, which means they absorb a different part of the light spectrum and thus can complement silicon cells to provide even greater combined efficiencies. But even using only perovskite, Yoo says, “what we’re demonstrating is that even with a single active layer, we can make efficiencies that threaten silicon, and hopefully within punching distance of gallium arsenide. And both of those technologies have been around for much longer than perovskites have.”

One of the keys to the team’s improvement of the material’s efficiency, Bawendi explains, was in the precise engineering of one layer of the sandwich that makes up a perovskite solar cell — the electron transport layer. The perovskite itself is layered with a transparent conductive layer used to carry an electric current from the cell out to where it can be used. However, if the conductive layer is directly attached to the perovskite itself, the electrons and their counterparts, called holes, simply recombine on the spot and no current flows. In the researchers’ design, the perovskite and the conductive layer are separated by an improved type of intermediate layer that can let the electrons through while preventing the recombination.

This middle electron transport layer, and especially the interfaces where it connects to the layers on each side of it, tend to be where inefficiencies occur. By studying these mechanisms and designing a layer, consisting of tin oxide, that more perfectly conforms with those adjacent to it, the researchers were able to greatly reduce the losses.

The method they use is called chemical bath deposition. “It’s like slow cooking in a Crock-Pot,” Bawendi says. With a bath at 90 degrees Celsius, precursor chemicals slowly decompose to form the layer of tin dioxide in place. “The team realized that if we understood the decomposition mechanisms of these precursors, then we’d have a better understanding of how these films form. We were able to find the right window in which the electron transport layer with ideal properties can be synthesized.”

After a series of controlled experiments, they found that different mixtures of intermediate compounds would form, depending on the acidity of the precursor solution. They also identified a sweet spot of precursor compositions that allowed the reaction to produce a much more effective film.

The researchers combined these steps with an optimization of the perovskite layer itself. They used a set of additives to the perovskite recipe to improve its stability, which had been tried before but had an undesired effect on the material’s bandgap, making it a less efficient light absorber. The team found that by adding much smaller amounts of these additives — less than 1 percent — they could still get the beneficial effects without altering the bandgap.

The resulting improvement in efficiency has already driven the material to over 80 percent of the theoretical maximum efficiency that such materials could have, Yoo says.

While these high efficiencies were demonstrated in tiny lab-scale devices, Bawendi says that “the kind of insights we provide in this paper, and some of the tricks we provide, could potentially be applied to the methods that people are now developing for large-scale, manufacturable perovskite cells, and therefore boost those efficiencies.”

In pursuing the research further, there are two important avenues, he says: to continue pushing the limits on better efficiency, and to focus on increasing the material’s long-term stability, which currently is measured in months, compared to decades for silicon cells. But for some purposes, Bawendi points out, longevity may not be so essential. Many electronic devices such as cellphones, for example, tend to be replaced within a few years anyway, so there may be some useful applications even for relatively short-lived solar cells.

“I don’t think we’re there yet with these cells, even for these kind of shorter-term applications,” he says. “But people are getting close, so combining our ideas in this paper with ideas that other people have with increasing stability could lead to something really interesting.”

Robert Hoye, a lecturer in materials at Imperial College London, who was not part of the study, says, “This is excellent work by an international team.” He adds, “This could lead to greater reproducibility and the excellent device efficiencies achieved in the lab translating to commercialized modules. In terms of scientific milestones, not only do they achieve an efficiency that was the certified record for perovskite solar cells for much of last year, they also achieve open-circuit voltages up to 97 percent of the radiative limit. This is an astonishing achievement for solar cells grown from solution.”

The team included researchers at the Korea Research Institute of Chemical Technology, the Korea Advanced Institute of Science and Technology, the Ulsan National Institute of Science and Technology, and Georgia Tech. The work was supported by MIT’s Institute for Soldier Nanotechnology, NASA, the Italian company Eni SpA through the MIT Energy Initiative, the National Research Foundation of Korea, and the National Research Council of Science and Technology.

School of Science presents 2021 Infinite Expansion Awards

by School of Science |

This year, the MIT School of Science has recognized 13 postdocs and research scientists who are the recipients of the 2021 Infinite Expansion Award.

The award, formerly called the “Infinite Kilometer Award,” was created in 2012 to highlight the contributions of important members of the MIT science community. The awardees are nominated for their contributions to their research labs, participation in educational programs, exceptional talent, generous character, service to the community, teamwork, and in general, going above and beyond in their roles at the Institute, especially during the coronavirus pandemic.

The following are the 2021 School of Science Infinite Expansion winners:

  • Xinqiang Ding, a postdoc in the Department of Chemistry, nominated by Assistant Professor Bin Zhang for “being one of the most promising, talented, and hard-working scientists that [he has] worked with in [his] entire career”;
  • Quentin Ferry, a postdoc in the Picower Institute for Learning and Memory, nominated by Professor Susumu Tonegawa for “remarkable raw talent, versatility … a highly motivated attitude, deep critical thinking, and an extremely creative personality”;
  • Hamed Owladeghaffari, a postdoc in the Department of Earth, Atmospheric and Planetary Sciences, nominated by Assistant Professor Matěj Peč for “consistently gone above and beyond his duty”;
  • Andrew Grassetti, a postdoc in the Department of Biology, nominated by Assistant Professor Joseph Davis for “[going] well beyond any reasonable expectations to ensure that my entire group has the support — scientific, professional, and emotional — that they needed to succeed”;
  • Sarah Heine, a research scientist in the MIT Kavli Institute for Astrophysics and Space Research (MKI), nominated by Principal Research Scientist Herman Marshall for “[being] a major contributor”;
  • Samantha Kristufek, a postdoc in the Department of Chemistry, nominated by Professor Jeremiah Johnson for “cultivating an inclusive, supportive group culture”;
  • Nathan Lourie, a research scientist in the MIT Kavli Institute for Astrophysics and Space Research, nominated by Professor and MKI Director Rob Simcoe for “demonstrat[ing] both a high degree of personal grit, a capacity to build and lead a team, and a high degree of community engagement”;
  • Hiruy Meharena, a postdoc in the Picower Institute for Learning and Memory, nominated by Professor and Picower Institute Director Li-Huei Tsai for “being a community builder and exemplary scientific colleague”;
  • Alexander Schuppe, a postdoc in the Department of Chemistry, nominated by Professor Stephen Buchwald for “consistent and significant positive impact on the research efforts of others”;
  • Jitendra Sharma, a research scientist in the Picower Institute for Learning and Memory, nominated by administrative manager Eleanor MacPhail, postdoc Grayson Sipe, and Professor Mriganka Sur for “willingness to help everyone,” “serves as a beacon of optimism and collegiality,” and “approach[ing] each day with the goal of making a difference that will help advance the MIT mission”;
  • Yong Wang, a postdoc in the Department of Chemistry, nominated by Assistant Professor Alison Wendlandt for “[being] an exceptionally talented scientist, a committed mentor, and a model coworker”;
  • Jun Yang, a postdoc in the Department of Physics and MIT Kavli Institute for Astrophysics and Space Research, nominated by Professor Or Hen, professor and physics head Peter Fisher, and Research Scientist Norbert Shulz for “community building,” “mak[ing] a difference,” and “[making] great efforts to organize events for the physics postdoc association during a time of isolation”; and
  • Hannah Yevick, a research scientist in the Department of Biology, nominated by Associate Professor Adam Martin for “devotion to mentoring.”

The honor includes a monetary award and will be commemorated in person at a later date with family, friends, and nominators, as well as the winners of the 2021 Infinite Mile Award.

Scientists as engaged citizens

by School of Humanities, Arts, and Social Sciences |

The classroom in fall 2020 looked very different than it did when WGS.160/STS.021 (Science Activism: Gender, Race, and Power) ran for the first time in 2019. Zoom and virtual breakout rooms had replaced circles of chairs, but the shifts made the class no less immersive and urgent for its students.

In fact, the pandemic context made the core questions of this new survey class all the more vivid: What roles have U.S. scientists and technologists played as activists in crucial social issues and movements following WWII? What are their motivations, responsibilities, and strategies for organizing? What is their impact?

Scientists have been on the front lines of active citizenship and policy engagement in recent years in very visible ways — in the People’s Climate Movement, in controlling the global Covid-19 pandemic, and in testimony about biases in facial recognition in Congress, to name just a few.

As students in the Science Activism class have learned, this engagement isn’t a new phenomenon. There is a long history of scientists championing important issues, policy positions, and public education by contributing their scientific knowledge and perspectives. Case studies in this course include the civil rights movement, the nuclear freeze campaign, climate science and action, environmental justice, Vietnam War protests, the March 4 Movement at MIT, and advocating for gender equality in STEM fields.

Reflecting the layered and intersecting issues this class explores, it is listed in both the Program in Women’s and Gender Studies (WGS) and in the MIT Program in Science, Technology, and Society.

From the research bench to the policy table

Scientific knowledge is now critical for public understanding and sound policy for most of today’s most critical issues — from climate to human health to food security — and MIT students are eager to understand how their works interact with social realities and how they can lend their expertise to advancing better conditions and policies.

“The class was informed by the increasing efforts by scientists to engage in public policy not only at the ballot box, or by providing testimony,” says Ed Bertschinger, professor of physics, who led the initial class in 2019 as well as the 2020 class. “More scientists are also taking up causes of activism. That’s been true at MIT and around the country.”

As a faculty affiliate of the WGS program, Bertschinger notes that science has never been purely objective or detached from society. “Activism is a way for groups with less power in democratic societies to have their voices heard in order to effect change,” he observes. “Scientists can no longer take for granted that their results speak for themselves.”

Bertschinger recalls that his first experience with activism was in graduate school, in the 1980s, when he served as an organizer for the Nuclear Weapons Freeze Campaign. “I was following the lead of an MIT group,” reflects Bertschinger, “including scholars such as the late Randall Forsberg and Philip Morrison, who were leaders in the nuclear disarmament effort in the U.S.”

Bridging the gap

His students now are similarly broadening their areas of academic interest into awareness of the context, impact, and influence their respective fields have in society.

For Eleane Lema, a senior majoring in chemistry/biology and minoring in anthropology, the draw of Science Activism came from a sense of disconnection between her academic life as a scientist and her drive to make a positive social impact. The class subjects dovetail with her explorations of environmental justice and the unequal benefits and harms scientific change has for different communities.

Taking MIT’s mission “for the betterment of humankind” to heart since her first year at the Institute, Lema seeks ways to combine her technical education and her wish to engage in meaningful social work. This past summer, for instance, she had a health policy internship through MIT’s Washington Internship program, a longstanding initiative led by Charles Stewart III, the Kenan Sahin Distinguished Professor of Political Science, and founding director of the nonpartisan MIT Election Data and Science Lab.

“WGS.160 is an opportunity to learn about the positive influences scientists have made in addressing the world’s biggest challenges,” says Lema. “By bridging science and social issues, this class shows us real, practical ways to embody MIT’s mission to serve humankind.”

A duty to learn

Emily Condon, another senior in the class this fall, also sees WGS.160 as an opportunity to understand her own social responsibilities as a scientist. “With the recent Black Lives Matter movement events and the current political climate, I felt a responsibility to educate myself on what I, as a student of science and engineering, could contribute to ending violence and discrimination against Black communities.”

“The most profound idea that I’ve learned in this class is that science is not entirely objective,” reflects Condon. “There are always biases about what science implies or what scientific problems are important to study. Providing more spaces for BIPOC scientists to direct the course of research is essential to diversifying perspectives and approaches to science.”

Condon followed the tangible effects of such biases as she studied the material impacts of climate change and its roots as a social, as well as a scientific, problem. “Underserved communities are disproportionately impacted by the negative effects of climate change, and recognizing that can help scientists and engineers direct efforts to aid the people in those communities.”

For senior Kate Pearce, who is majoring in computer science and biology with a minor in math, the class is a chance to connect her longtime interest in science and activism. It has also given her a greater sense of continued agency over her own technical projects by learning how scientists have been able to anticipate and influence how their innovations will impact people, rather than simply allowing political and economic systems to determine how their work will be used.

The class, in both runs to date, has been composed primarily of MIT undergraduates focused on technical fields.

Like their professor, the students come to the WGS program as interdisciplinary thinkers, pursuing a fuller and more nuanced sense of their work’s place in a volatile world. The program is designed to enable just that understanding — drawing on expertise across the Institute, from physicists to philosophers to poets, to provide analytical frameworks for the examination of gender, race, ethnicity, class, and sexuality — and how these aspects of human identity intersect with the life and issues of society.

“The feminist lens of Science Activism really intrigued me,” Pearce adds, “especially as applied to how science and social change are motivated and executed.”

An active MIT history

Topics in Science Activism take a broad view of recent decades, examining Vietnam War protests by scientists, genetic engineering, and the birth of modern environmentalism in the United States. There is a special focus on activism at MIT in particular, from the 1960s to present, including the March 4 Movement.

That movement began in 1969, when research and regular teaching at MIT slowed as students, faculty, and staff paused to protest the war in Vietnam and the Institute’s links to the military. Similar themes echo to the present day, with students, faculty, and staff opposing military solutions to international conflicts and broadening MIT’s engagement into social and economic justice.

For Lema, the course has also provided insight into what successful activism looks like in projects like bringing awareness to the climate crisis. “MIT has played an integral role in the history of science activism, and I hope every MIT student gets the opportunity to learn about this history and discover how they can become activists for causes they are passionate about.”

Joining the conversation

Like many of MIT’s humanistic courses, Science Activism is discussion-based: students build a foundational understanding from assigned readings and come to the classroom (live or virtual) prepared to debate and discuss. Guest speakers, such as Harvard Medical School Professor Jon Beckwith, who has led a Harvard University course focused on activism and the life sciences, broadened and deepened the conversation in the class’s first iteration by adding the perspectives of specialists in different disciplines.

This year the class welcomed via Zoom a number of new guest speakers, including Jin In, an advocate for women’s empowerment; Arwa Mboya, a former research assistant at the MIT Media Lab; and Steve Penn, a prominent MIT activist of the 1980s and ’90s. As a discussion-based class, the students’ insights are the engine of the class experience, and Bertschinger dedicates the majority of class time to breakout rooms so each student has a chance to thoroughly engage with ideas and questions.

“I have been so impressed by the passion and insight that my peers in this class provide,” says Pearce. “Since people are so engaged and passionate about these topics, the breakout rooms always lead to wonderful discussions, and we must struggle to end as the timer ticks down.”

For instance, the climate crisis — one of the foremost issues of the students’ lives — inspires intense, far-ranging conversations as class members trace the roots of environmentalism and think together about how best to respond to the multi-faceted crisis. The students’ experience gives the course an ever-expanding horizon as students’ insights widen discussions around intersectional equality in the sciences and in society.

“It was a great pleasure to teach the class last year; I learned a lot from working with the students and from developing case studies,” reflects Bertschinger. “It’s important for the MIT community to pay attention to the activism on campus — and to help our students develop the wisdom and the capacity to use their voices to the fullest effect in the world.”

Story by MIT SHASS Communications
Editorial team: Alison Lanier and Emily Hiestand

Donated instrument provides undergraduate chemistry students high-level research experience

by Steve Nadis | MIT.nano |

Beta defensins are a class of antimicrobial peptides that vary in size from 61 to 183 amino acids. More than 3,000 beta defensins had been identified prior to this year — until undergraduates in a lab class taught by associate professor of chemistry Bradley Pentelute synthesized some that had never been synthesized or characterized before.

Part of the interest in these peptides stems from their potential ability to elicit an immune response to pathogens. Pentelute is collaborating in this project with researchers at Massachusetts General Hospital, and the beta defensins synthesized by the students will be tested in the hopes that some may lead to new varieties of antibiotics — a high priority in an era when antibiotic resistance is becoming an urgent concern.

When the students needed to analyze their peptides, they turned to a powerful instrument reserved just for their use: the Ultra Performance Liquid Chromatography-Mass Spectrometer (UPLC-MS) from Waters Corp. Installed this year in the Undergraduate Teaching Laboratories (UGTL) of MIT’s Department of Chemistry, this instrument has a modest profile — the size, say, of two pairs of standard printers stacked on a desk — but it’s having an uncommonly large impact on the undergraduate research experience.

“It’s a very effective piece of equipment, and it’s rare to have a cutting-edge tool like this reserved exclusively for undergraduates,” says John Dolhun, director of the UGTL. “Undergraduate students can learn new analytic techniques in chemical biology and other areas that they normally wouldn’t encounter until graduate school or upon taking a job in industry. That makes for an eye-opening experience.”

The UPLC-MS combines two analytical techniques in a single tool: liquid chromatography, which physically separates a sample into its constituent parts, and mass spectrometry, which identifies the mass, composition, and chemical structure of the individual components. Another example of how students employ this capability came during the fall 2020 semester. Students taking class 5.362 (Kinetics of Enzyme Inhibition) used the LC-MS to confirm the presence of both phosphorylated and unphosphorylated peptides in a reaction of ABL kinase with a target peptide and an inhibitor, Gleevec. Previously, students had no way of knowing whether this reaction worked during the experiment.

Research of this sort is facilitated by the fact that the machine is fast, efficient, and easy to use, says Dolhun. “It’s all automated,” he says. “After loading the samples, students can get their spectrum very quickly, typically within 10 to 15 minutes. That means they can accomplish much more in each lab session, while having more time to analyze and discuss the data they’ve obtained.” And there’s an added bonus, he says. “Anything that gives them a faster result can free up their brains for the next project.”

The teaching labs occupy the top floor of MIT.nano (Building 12), a five-story, 214,000-square-foot facility that opened in fall 2018, providing more than 100,000 square feet of laboratory space devoted to the study of materials, devices, and phenomena at the scale of atoms and molecules.

The UPLC-MS was donated by the Waters Corporation, a Massachusetts-based scientific equipment company that also helped with the installation and maintenance of the instrument, as well as the training for its use. Waters is a founding member of the MIT.nano Consortium, a group of 14 companies drawn from industries around the globe interested in nanoscale discoveries and innovations emerging from MIT.

“MIT.nano and the chemistry teaching labs are the only two occupants of Building 12, leading to close collaborative bond and a strong partnership between MIT.nano and the Department of Chemistry,” says Vladimir Bulović, faculty director of MIT.nano. “When the opportunity arose to help steer Waters’ contribution to the UGTL, we were delighted to collaborate in this effort to enhance undergraduate education at MIT.”

The UPLC-MS also offers environmental advantages. Because the machine operates at pressures more than twice those used in more typical high-performance counterparts, with higher efficiency column design and substantially lower flow rates, it can work with samples up to 400 times smaller in volume. “That means that orders-of-magnitude less solvent is required,” says Whitney Hess, MIT.nano’s manager of safety systems and programs, “which leads to much less waste overall.”

Waste minimization and green chemistry strategies were, in fact, among the criteria that led to the UGTL winning the 2020 SafetyStratus Award from the American Chemical Society (ACS) in recognition of the most comprehensive chemical safety programs in higher education. Hess, who partnered with Dolhun in crafting the MIT nomination for the ACS award, says the UGTL has taken other steps to implement green chemistry practices, including green chemistry-focused lab curricula, the recycling of solvents, and switching from older, inefficient equipment to newer models that generate less waste.

On the research front, Dolhun says, “Now that we’ve seen what the UPLC-MS can do, we’re striving to come up with novel ways of utilizing this machine. It has prompted us, moreover, to seek out other pieces of equipment that should be brought into the labs to further challenge our students and accelerate their education.”