Author: MIT News

Five MIT faculty elected 2021 AAAS Fellows

by MIT News Office |

Five MIT faculty members have been elected as fellows of the American Association for the Advancement of Science (AAAS).

The 2021 class of AAAS Fellows includes 564 scientists, engineers, and innovators spanning 24 scientific disciplines who are being recognized for their scientifically and socially distinguished achievements.

Mircea Dincă is the W. M. Keck Professor of Energy in the Department of Chemistry. His group’s research focuses on addressing challenges related to the storage and consumption of energy, and global environmental concerns. Central to these efforts are the synthesis of novel organic-inorganic hybrid materials and the manipulation of their electrochemical and photophysical properties, with a current emphasis on porous materials and extended one-dimensional van der Waals materials.

Guoping Feng is the James W. and Patricia T. Poitras Professor of Neuroscience in the Department of Brain and Cognitive Sciences, associate director of MIT’s McGovern Institute for Brain Research, director of Model Systems and Neurobiology at the Stanley Center for Psychiatric Research, and an institute member of the Broad Institute of MIT and Harvard. His research is devoted to understanding the development and function of synapses in the brain and how synaptic dysfunction may contribute to neurodevelopmental and psychiatric disorders. By understanding the molecular, cellular, and circuitry mechanisms of these disorders, Feng hopes his work will eventually lead to the development of new and effective treatments for the millions of people suffering from these devastating diseases.

David Shoemaker is a senior research scientist with the MIT Kavli Institute for Astrophysics and Space Research. His work is focused on gravitational-wave observation and includes developing technologies for the detectors (LIGO, LISA), developing proposals for new instruments (Cosmic Explorer), managing the teams to build them and the consortia which exploit the data (LIGO Scientific Collaboration, LISA Consortium), and supporting the overall growth of the field (Gravitational-Wave International Committee).

Ian Hunter is the Hatsopoulos Professor of Mechanical Engineering and runs the Bioinstrumentation Lab at MIT. His main areas of research are instrumentation, microrobotics, medical devices, and biomimetic materials. Over the years he and his students have developed many instruments and devices including: confocal laser microscopes, scanning tunneling electron microscopes, miniature mass spectrometers, new forms of Raman spectroscopy, needle-free drug delivery technologies, nano- and micro-robots, microsurgical robots, robotic endoscopes, high-performance Lorentz force motors, and microarray technologies for massively parallel chemical and biological assays.

Evelyn N. Wang is the Ford Professor of Engineering and head of the Department of Mechanical Engineering. Her research program combines fundamental studies of micro/nanoscale heat and mass transport processes with the development of novel engineered structures to create innovative solutions in thermal management, energy, and water harvesting systems. Her work in thermophotovoltaics was named to Technology Review’s lists of Biggest Clean Energy Advances, in 2016, and Ten Breakthrough Technologies, in 2017, and to the Department of Energy Frontiers Research Center’s Ten of Ten awards. Her work extracting water from air has won her the title of 2017 Foreign Policy’s Global ReThinker and the 2018 Eighth Prince Sultan bin Abdulaziz International Prize for Water.

Encapsulation as a method for preventing degradation in Li-air batteries

by Crystal Koe | Department of Chemistry |

Lithium-air batteries were thought promising in the 1970s as a potential power source for electric vehicles, offering energy densities that rival gasoline and significantly surpass conventional lithium-ion batteries. However, scientists over the last few decades have been unable to overcome challenges to practical application of this technology, including reversible charging and low cyclability that results in battery degradation over few uses.

A research team from MIT, Harvard University, and Cornell University has found a way to isolate and study one enigmatic molecule that may be responsible for the breakdown of key components in Li-air batteries — lithium superoxide.

“The key to trapping lithium superoxide is by using a confining shell of quinone—a molecule used as an energy carrier in biology,” says Matthew Nava PhD ’17, lead author of a paper on the work, published recently in PNAS. Nava, who is now a postdoc at Harvard University working in the laboratory of Patterson Rockwood Professor of Energy Daniel G. Nocera, contributed to the work as a researcher in the lab of Henry Dreyfus Professor of Chemistry Christopher Cummins, who is a senior author of the study; along with Shiyu Zhang from MIT; Katharine Pastore and Kyle Lancaster from Cornell University; and Xiaowen Feng and Daniel Nocera of Harvard.

Like many discoveries, this one began as an accident. While a graduate student in the Cummins group, Nava noticed that lithium peroxide turned blue when it got close to quinone, representing a rare color change of two reactant solids. Although they knew that the lithium superoxide intermediate should be present in this new material, it was difficult to prove, as the intermediate was buried in a shell of highly colored quinone, prone to detonation.

Lithium–air batteries operate by electron transfer from a high-surface-area cathode to oxygen gas during discharge, generating lithium peroxide deposits, the crucial storage material for this class of batteries. Lithium superoxide, formed during charging and discharging, is too unstable and short-lived at room temperature for scientists to reliably study; thus, being able to generate and stabilize this crucial intermediate is an important step toward developing a viable lithium-air battery.

“The limited cyclability [of li-air batteries] indicate that our understanding of the metal oxides that form the energy storage unit of these batteries is incomplete,” says Nava. “This work demonstrates how encapsulation or physical confinement with specific materials might be a powerful method to prevent electrolyte and cell degradation in these batteries and increase cell cyclability.”

As the world slowly transitions to renewable energy sources, problems of intermittency and the challenges of converting renewable energy into usable fuels need to be solved. Batteries may play a crucial role in the need for reliable and efficient energy storage, and this discovery may have provided a vital key to unlocking the way forward.

Synthesis too slow? Let this robot do it.

by Crystal Koe | Department of Chemistry |

Researchers in the lab of Bradley Pentelute, MIT Professor of Chemistry, have invented a fully automated fast-flow instrument that can synthesize peptide-nucleic acids in a single shot.

By automating the process of synthesizing CPP-conjugated peptide-nucleic acids (PPNAs) using the robot dubbed “Tiny Tides” by the research team, typical PPNA synthesis time was reduced from multiple days to just two hours.

“This new efficient technology represents a potential major step forward to enable on-demand rapid production of candidate antisense oligonucleotides, not only for Covid-19 but also for other diseases and emerging pathogens,” says Chengxi Li, a co-author of the paper and a postdoc in the Pentelute Group.

The paper, “Automated Flow Synthesis of Peptide−PNA Conjugates,” was recently published in ACS Central Science.

What are PNAs?

PNAs are artificially synthesized DNA-like molecules with a wide range of chemical and biological applications, emerging as a class of therapies being used to treat various diseases from cancer to viral infections. Barriers to PNAs becoming a drug include low solubility, poor cellular uptake, and rapid elimination.

Some of these challenges have been addressed with the covalent attachment of cell-penetrating peptides (CPP) to a PNA. However, CPP-conjugated PPNAs can be toxic to cells and often require time-consuming structure-function studies to minimize toxicity while optimizing delivery. In addition, although standard batch protocols allow for efficient access to PNA sequences of fewer than 15 bases, longer sequences are challenging to synthesize and face limitations that can result in low yields.

“Let the robot do it”

The automated fast-flow device, designed by the Pentelute Group to replace traditional stepwise synthesis via click chemistry, consists of seven modules including a central control computer, solution storage system, three HPLC pumps, three multiposition valves, heating elements, reaction zone, and a UV-vis detector — all controlled by a modular script in the Mechwolf programming environment.

The research team decided on the name Tiny Tides for two reasons: their robot makes peptides or oligonucleotides, and is a micro-scale synthesizer capable of rapid condition optimization and synthesis using a low amount of reagent and solvent, a comparatively tiny cost.

Despite the moniker, performance is anything but tiny. In lab tests, Tiny Tides reported 10 seconds for each amide bond formation between PNA monomers — compared with 10 minutes per amide bond for microwave peptide synthesizers; or 32 minutes per coupling cycle as with the DNA synthesizer Expedite 8909 capped at room temperature. Tiny Tides’ variable temperature design also eliminates the need for temperature capping, while increasing coupling efficiency.

This production strategy is convenient for simultaneous investigation of the bioactivity, toxicity, and cell uptake of multiple PNAs. In addition, the speed and automation of this device allows for a high throughput investigation of multiple candidates to find the most effective PNA sequence for a target, with significantly improved speeds over current and commercial methods.

Fight against Covid-19

While breakthroughs in vaccine science have taken center stage in the global Covid-19 pandemic, direct-acting antiviral agents could be another tool to eliminate this virus. In the lab, PNAs have demonstrated efficacy against SARS-CoV; and the high sequence similarity to SARS-CoV-2, the virus that causes Covid-19, has led researchers to believe that antisense PNAs may well be a way to achieve SARS-CoV-2 inhibition.

Speed and efficiency in synthesizing PPNAs is a much-needed step toward being able to evaluate the numerous possible sequences for viability in treating disease. For this study, the Pentelute group chemically synthesized eight PPNAs to combat Covid-19 in just one day — a feat which would have taken nearly a month if synthesized manually at a rate of two per week using previous methods.

Of the eight, one sequence eliminated over 95 percent of the virus in a live infection assay.

Other contributing authors are affiliated with MIT and Iowa State University.

From counting blood cells to motion capture, sensors drive patient-centered research

by Becky Ham | MIT.nano |

Sensors and sensing systems — from devices that count white blood cells to technologies that monitor muscle coordination during rehabilitation — can positively impact medical research, scientists said at the 2021 SENSE.nano Symposium.

The virtual event focused on how sensing technologies are enabling current medical studies and aiding translation of their findings to improve human health. Featuring leaders from research and industry, MIT-launched startup companies, and graduate students, the event was the fifth annual meeting organized by SENSE.nano.

“In this era of big data, sensors are everywhere — in our homes and vehicles, medical devices, phones, and even clothing,” says MIT.nano Director Vladimir Bulović. “This year’s symposium was an exploration of how this breadth of new sensors and new sensing techniques will propel the standards of current medical work, bringing forward new clinical practice and better health for all.”

The SENSE.nano 2021 speakers discussed a range of technologies under the research themes of human motion studies, physiological monitoring, imaging at multiple scales, and devices and strategies for collecting specimens and performing biopsies. Presenters described novel research methods — such as drawing inspiration from dancers’ movement to study how muscles represent rhythm — and novel applications such as neural interface wearables to help humans better interact with robots and other electronic systems.

The symposium also celebrated the re-opening of the MIT Center for Clinical and Translational Research (CCTR, formerly the MIT Research Clinical Center). Along with remodeled health labs for research participants, the CCTR features a prototype workshop, motion capture lab, and observation and instrumentation suites for MIT and visiting human health researchers.

“SENSE.nano 2021 brought together nanoscience, nanotechnology, and the practice of medicine through our shared and central facilities — MIT.nano and the new CCTR,” says Brian Anthony, the associate director of MIT.nano and principal research scientist in the Department of Mechanical Engineering. “MIT.nano has the tools to support fabrication and design of sensors, and the CCTR has the clinical research space to study how these sensors can support medical practice.”

The patient-centered application of many sensing technologies used in medical research, including motion capture and wearable analytic devices, makes it more important than ever to include patients as active participants in such research, said keynote speaker Cecilia Stuopis, medical director of MIT Medical.

“We want the evaluation of questions and outcomes meaningful and important to patients and caregivers to be central to the process, because we want to recognize that they have unique perspectives, values, and goals for what we are trying to learn or accomplish,” Stuopis said.

Encouraging collaborative relationships between researchers and health-care providers has the potential to shorten the usual 17-year gap between basic research and its widespread acceptance in the clinic, she added, in part by connecting researchers with underserved populations who may not normally participate in clinical trials.

The symposium featured speakers from more than 10 MIT departments, labs, or centers (DLCs), including mechanical engineering, biological engineering, chemistry, and computer science and artificial intelligence. Their presentations underscored the multidisciplinary reach of sensors research. Mechanical engineering Associate Professor Jeehwan Kim demonstrated a perforated electronic skin, which can collect physiological data from the body without being damaged by sweat. Inspired by her grandmother’s stroke, Kaymie Shiozawa, a mechanical engineering graduate student, shared her work on human balance that she hopes will lead to a new robotic cane. In the imaging session, Lester Wolfe Professor of Chemistry Moungi Bawendi discussed a noninvasive method of using near-infrared and shortwave infrared to track the progression of liver disease.

As in previous years, SENSE.nano 2021 also highlighted the innovation ecosystem at MIT, with presentations by MIT-launched startups working to grow their ideas to scale.

MIT.nano and the CCTR are united by their active engagement with startup companies, said Brian Anthony. For instance, ongoing studies at the center have helped Leuko, a startup that makes a device for non-invasive, at-home white blood cell monitoring, refine and improve its product. Leuko was one of three medical sensor startups featured in this year’s symposium, along with Pison Technology and Stratagen Bio.

SENSE.nano 2021 was sponsored by MIT.nano, the MIT Industrial Liaison Program, and the MIT Center for Clinical and Translational Research.

Measuring cancer cell state can reveal drug susceptibility

by Anne Trafton | MIT News Office |

Over the past few decades, scientists have made great strides in understanding the genetic mutations that can drive cancer. For some types of cancer, these discoveries have led to the development of drugs that target specific mutations.

However, there are still many types of cancer for which no such targeted therapies are available. A team of researchers from MIT, Dana Farber Cancer Institute, and other institutions is now examining whether another cell trait — RNA expression patterns — influences drug responses and can be used to identify treatments a tumor might be susceptible to.

In a new study of pancreatic cancer cells, the researchers identified three prototypical RNA-expression states and uncovered differences in their susceptibility to a variety of cancer drugs. They also discovered that altering the tumor microenvironment can drive tumor cells from one state to another, potentially offering a way to make them more susceptible to a particular drug.

“What we show in this paper is that cancer cell state is plastic in response to the microenvironment and has a dramatic impact on drug sensitivity. This opens new frontiers for thinking about drug development and how to select drugs for individual patients,” says Alex Shalek, a core member of the Institute for Medical Engineering and Science (IMES) at MIT, an associate professor of chemistry, and an extramural member of MIT’s Koch Institute for Integrative Cancer Research. He is also a member of the Ragon Institute of MGH, MIT and Harvard and an institute member of the Broad Institute.

Shalek and Brian Wolpin, an associate professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute; William Hahn, a professor of medicine at Harvard Medical School and Dana-Farber; and Andrew Aguirre, an assistant professor of medicine at Harvard Medical School and Dana-Farber; are the senior authors of the study, which appears today in Cell. The paper’s lead authors are Srivatsan Raghavan, an instructor in medicine at Harvard Medical School and Dana-Farber; Peter Winter, an MIT postdoc; Andrew Navia, an MIT graduate student; and Hannah Williams, a research fellow in medicine at Harvard Medical School and Dana-Farber.

Cell states

Sequencing a cell’s genome can reveal cancer-linked mutations, but identifying these mutations doesn’t always provide information that can be acted upon to treat a particular tumor. To generate additional data that could be used to help choose more targeted treatments, Shalek and other researchers have turned to single-cell RNA-sequencing, which reveals the genes that are being expressed by each cell at a moment in time.

“There are plenty of situations where the genetics are incredibly important, where you can develop these very precise drugs that target mutations or translocations,” Navia says. “But in many instances mutations alone don’t give you an effective way to target cancer cells relative to healthy ones.”

In this study, the researchers analyzed cells from pancreatic ductal adenocarcinoma (PDAC). There are very few targeted drugs available to treat pancreatic tumors, so most patients receive chemotherapy drugs that may be effective initially but often stop working as tumors become resistant. Using single-cell RNA-sequencing, the researchers analyzed about 25 metastatic tumor samples from pancreatic cancer patients.

Previous analyses of pancreatic tumor cell RNA have revealed two broad categories of cell states: basal-like, which is a more aggressive state, and classical. In the new study, the researchers identified a third state that appears to be an intermediate between those two. Cancer cells may pass through this state as they transition from classical to basal-like, the researchers say.

The researchers also found that the environment in which cancer cells are grown plays a key role in determining their state. In this study, they grew matched “organoids,” or tiny cancer aggregates from each patient’s biopsy. Such organoids are often used in precision medicine pipelines to model tumors from individual patients, to help identify drugs that might be useful for those individuals.

When comparing each in vivo single-cell profile to the matched ex vivo organoid model, the researchers found that the organoids often exist in a different RNA state than cancer cells examined directly from the same patient. “We see the same DNA mutations in the original tumor and its model, but when we start to examine what they look like at the RNA level, we find that they’re very, very different,” Shalek says.

That suggests that the state of a tumor can be influenced by the conditions in which it’s grown rather than its genetics alone, he says. The researchers also found that they could drive cancer cells, even long-established cell line models, to switch between different states by changing their growth conditions. Treating cells with TGF-beta, for example, drives them to a more aggressive, basal-like state, while taking TGF-beta away leads the cells to revert to the classical state in a dish.

Cells in each of those states depend on different cell-signaling pathways to survive, so knowing the cell state is critical to selecting the right kind of drug to treat a particular tumor, the researchers say.

“When we started looking at drug sensitivity, it became very clear that the same model pushed into a different state would respond very differently to a drug,” Navia says. “These state-specific sensitivities become critical as we think about selecting drugs and avoiding resistance. If you don’t know the right state, you could pick the entirely wrong compound and try to target the wrong pathways. If you don’t consider plasticity, the cancer may only respond temporarily until its cells change state.”

Targeted therapy

The findings suggest that further analyzing the interplay of genetics, cell state, and the tumor microenvironment could help researchers to develop new drugs that would effectively target individual patients’ tumors.

“We’re not erasing decades of understanding cancer as a genetic disease, but we’re certainly saying that we need to much better understand the intersection between genetics and state,” Winter says. “Cell state absolutely has ties to the underlying sensitivity of certain models, and therefore patients and to specific drugs.”

The discovery that cancer cells can be driven from one state to another by modifying the signals in their microenvironment raises the possibility of  locking cancer cells into a particular state in a predictable way by therapeutically altering the tumor microenvironment, and then giving a separate drug to target that locked state and enhance treatment efficacy.

With their colleagues at Dana-Farber, the MIT team is now running much larger drug screens to measure how each drug affects pancreatic cancer cells in different states. They are also studying other types of cancer to determine if those cancer cells are also able to transition between different states in response to changes in their microenvironment.

The research was funded, in part, by the National Institutes of Health, the Koch Institute and Dana-Farber/Harvard Cancer Center Bridge Project, the Ludwig Center for Molecular Oncology at MIT, the Beckman Young Investigator Program, a Sloan Fellowship in Chemistry, and the Pew-Stewart Scholars Program for Cancer Research.

Chemist and MLK Jr. Scholar Robert Gilliard explores new frontiers in synthetic chemistry

by Leah Campbell | School of Science |

Almost 15 years ago, Robert Gilliard posed for a photo in front of MIT’s Great Dome. At the time, he was an undergraduate at Clemson University visiting MIT with his research advisor, former MIT postdoc and Clemson University professor Rhett Smith. Just last month, Gilliard arranged a similar photo in front of the dome. This time, though, he was the professor behind the camera, wrangling his own students. And now, Gilliard is back working in experimental chemistry alongside MIT Dreyfus Professor of Chemistry Christopher “Kit” Cummins with the 2021-22 cohort of Martin Luther King (MLK) Visiting Professors and Scholars.

As an MLK scholar at MIT, he’s one of nine professors, in research areas ranging from art to engineering, selected for outstanding contributions in their fields to increase the presence of underrepresented minority scholars at MIT.

In the decade since his first visit to MIT, Gilliard has become one of the brightest young scholars in chemistry. Most recently, he’s won a Packard Fellowship, an Alfred P. Sloan Research Fellowship, a grant from the Beckman Foundation Young Investigator Program, and an NSF CAREER Award. He was also named to the 2020 class of the “Talented Twelve,” an elite list of scholars identified by Chemical & Engineering News as rising stars in the world of chemistry.

Currently, Gilliard is an assistant professor of chemistry at the University of Virginia. He arrived at UVA after completing his PhD at the University of Georgia and a joint postdoc at ETH Zürich in Switzerland and Case Western Reserve University. Even before arriving at UVA, he had built up an impressive resume, having received postdoctoral fellowships from both the Ford Foundation and the UNCF-Merck Science Initiative dedicated to supporting the training and development of African-American biomedical scientists.

Despite his accomplishments, Gilliard humbly describes his professional path as essentially unplanned. He always liked science but admits that he was never “one of those kids with the chemistry set.” In fact, he enrolled at Clemson as pre-med. But it took only one day for him to switch to engineering, and only one semester to go from engineering to chemistry. Getting to do research as an undergraduate was the moment that his enjoyment of science became a desire to be a scientist.

Today Gilliard’s lab is pushing the boundaries of synthetic chemistry. He focuses on what are called main-group elements, those elements on the edges of the periodic table, like boron and beryllium, that have been traditionally understudied by chemists.

“Main group elements do a lot we didn’t know they could do,” according to Gilliard. “I think we are just now beginning to scratch the surface of what’s possible for these elements.”

Most of his research falls into two buckets. The first is what chemists call small molecule activation, in which they use relatively simple molecules to create new compounds that might be industrially useful. For example, Gilliard’s lab is focused on creating compounds that react with carbon dioxide, which could, in turn, help recycle the potent greenhouse gas from the atmosphere.

The other bucket of research is focused on thermochromic and thermofluorescent compounds, ones that can change color or light up depending on the temperature. Creating molecules that can visibly react to temperature changes provides a way to track ambient conditions without expensive analytical equipment, and, according to Gilliard, the applications for such compounds are endless. For example, soldiers could have uniforms that change color based on terrain they’re in. More immediately, the packaging around Covid-19 vaccines, which need to be stored at a certain temperature, could be developed to change color if it gets too warm and the vaccine is compromised.

Gilliard has no trouble describing potential applications to the compounds his lab is creating, but, for him, applications aren’t the priority. He’s motivated by the fundamental science, by the experimentation, and by the opportunity to create novel molecular structures and bonds that will have applications we can’t possibly predict.

“A lot of times in chemistry, you’re looking for one thing,” he says, “but then you find something that’s way cooler and much more important.”

It’s no surprise, then, that at MIT he’s developed a professional relationship with Cummins, who is Gilliard’s host during his visiting professorship. Cummins was the first seminar speaker Gilliard invited when he started at UVA and the one that introduced Gilliard to the MLK Scholars program at MIT.

Like Gilliard, Cummins sees himself as an “exploratory” chemist focused on creating interesting new molecules that have never been written about or that challenge the tenets of theoretical chemistry.

“Kit was just somebody who, throughout my time as a grad student and a postdoc, I just always, and I continue to, hold in such high regard,” says Gilliard. “It’s been a pleasure getting to know him even better since I’ve been here.”

Cummins speaks equally highly of Gilliard and says that he knew the young professor was a great candidate for the MLK Scholars Program as soon as they met. The two attend each other’s lab meetings and have already begun joint research combining the techniques that Cummins’s lab has developed with the novel molecules coming out of Gilliard’s work. Cummins hopes that their collaboration will result in interesting new chemical linkages that can have optical applications and catalyze other kinds of new reactions.

Cummins likens their relationship to a Reese’s Peanut Butter Cup: “two things that are great on their own, but they’re even better together.” He’s been thrilled to have Gilliard bring his insight to the lab and help his team brainstorm exciting new ideas and avenues for research.

“Sometimes my approach to science is a bit more analogous to improvisational jazz,” Cummins jokes. “I’ve always been so happy at MIT that there’s space for people like me and Robert who look at science in that way and view it as an outlet for our creative juices.”

Despite his accomplishments, Gilliard is quick to turn the conversation to those around him, like Cummins, who helped him get to this point in his career. Even before becoming a professor, there was the high school science teacher, Charlotte Godwin, who encouraged him with hands-on experiments and with whom he remains in contact. There was the professor at Clemson, Lourdes Echegoyen, who recommended he should give chemistry a try. And there was his undergraduate research advisor on whom Gilliard has modeled his own mentoring style. He also credits much of his success to the students in his lab, every one of whom he continues to meet with every week.

“I think one of the reasons why we have been able to produce the amount and quality of research that we’ve been able to produce is because we are in constant contact with each other,” Gilliard says. “We are able to solve problems faster together.”

Unsurprisingly then, Gilliard’s response when asked about his recent litany of accolades was simply, “I’m just happy for the students.”

How molecular clusters in the nucleus interact with chromosomes

by Anne Trafton | MIT News Office |

A cell stores all of its genetic material in its nucleus, in the form of chromosomes, but that’s not all that’s tucked away in there. The nucleus is also home to small bodies called nucleoli — clusters of proteins and RNA that help build ribosomes.

Using computer simulations, MIT chemists have now discovered how these bodies interact with chromosomes in the nucleus, and how those interactions help the nucleoli exist as stable droplets within the nucleus.

Their findings also suggest that chromatin-nuclear body interactions lead the genome to take on a gel-like structure, which helps to promote stable interactions between the genome and transcription machineries. These interactions help control gene expression.

“This model has inspired us to think that the genome may have gel-like features that could help the system encode important contacts and help further translate those contacts into functional outputs,” says Bin Zhang, the Pfizer-Laubach Career Development Associate Professor of Chemistry at MIT, an associate member of the Broad Institute of Harvard and MIT, and the senior author of the study.

MIT graduate student Yifeng Qi is the lead author of the paper, which appears today in Nature Communications.

Modeling droplets

Much of Zhang’s research focuses on modeling the three-dimensional structure of the genome and analyzing how that structure influences gene regulation.

In the new study, he wanted to extend his modeling to include the nucleoli. These small bodies, which break down at the beginning of cell division and then re-form later in the process, consist of more than a thousand different molecules of RNA and proteins. One of the key functions of the nucleoli is to produce ribosomal RNA, a component of ribosomes.

Recent studies have suggested that nucleoli exist as multiple liquid droplets. This was puzzling because under normal conditions, multiple droplets should eventually fuse together into one large droplet, to minimize the surface tension of the system, Zhang says.

“That’s where the problem gets interesting, because in the nucleus, somehow those multiple droplets can remain stable across an entire cell cycle, over about 24 hours,” he says.

To explore this phenomenon, Zhang and Qi used a technique called molecular dynamics simulation, which can model how a molecular system changes over time. At the beginning of the simulation, the proteins and RNA that make up the nucleoli are randomly distributed throughout the nucleus, and the simulation tracks how they gradually form small droplets.

In their simulation, the researchers also included chromatin, the substance that makes up chromosomes and incudes proteins as well as DNA. Using data from previous experiments that analyzed the structure of chromosomes, the MIT team calculated the interaction energy of individual chromosomes, which allowed them to provide realistic representations of 3D genome structures.

Using this model, the researchers were able to observe how nucleoli droplets form. They found that if they modeled the nucleolar components on their own, with no chromatin, they would eventually fuse into one large droplet, as expected. However, once chromatin was introduced into the model, the researchers found that the nucleoli formed multiple droplets, just as they do in living cells.

The researchers also discovered why that happens: The nucleoli droplets become tethered to certain regions of the chromatin, and once that happens, the chromatin acts as a drag that prevents the nucleoli from fusing to each other.

“Those forces essentially arrest the system into those small droplets and hinder them from fusing together,” Zhang says. “Our study is the first to highlight the importance of this chromatin network that could significantly slow down the fusion and arrest the system in its droplet state.”

Gene control
The nucleoli are not the only small structures found in the nucleus — others include nuclear speckles and the nuclear lamina, an envelope that surrounds the genome and can bind to chromatin. Zhang’s group is now working on modeling the contributions of these nuclear structures, and their initial findings suggest that they help to give the genome more gel-like properties, Zhang says.

“This coupling that we have observed between chromatin and nuclear bodies is not specific to the nucleoli. It’s general to other nuclear bodies as well,” he says. “This nuclear body concentration will fundamentally change the dynamics of the genome organization and will very likely turn the genome from a liquid to a gel.”

This gel-like state would make it easier for different regions of the chromatin to interact with each other than if the structure existed in a liquid state, he says. Maintaining stable interactions between distant regions of the genome is important because genes are often controlled by stretches of chromatin that are physically distant from them.

The research was funded by the National Institutes of Health and the Gordon and Betty Moore Foundation.

Getting quantum dots to stop blinking

by David L. Chandler | MIT News Office |

Quantum dots, discovered in the 1990s, have a wide range of applications and are perhaps best known for producing vivid colors in some high-end televisions. But for some potential uses, such as tracking biochemical pathways of a drug as it interacts with living cells, progress has been hampered by one seemingly uncontrollable characteristic: a tendency to blink off at random intervals. That doesn’t matter when the dots are used in the aggregate, as in TV screens, but for precision applications it can be a significant drawback.

Now, a team of chemists at MIT has come up with a way to control this unwanted blinking without requiring any modification to the formulation or the manufacturing process. By firing a beam of mid-infrared laser light for an infinitesimal moment — a few trillionths of a second — the quantum dot’s blinking is eliminated for a relatively long period, tens of billions of times longer than the laser pulse.

The new technique is described in a paper that appeared November 22 in the journal Nature Nanotechnology, by doctoral students Jiaojian Shi, Weiwei Sun, and Hendrik Utzat, professors of chemistry Keith Nelson and Moungi Bawendi, and five others at MIT.

Quantum dots are tiny particles, just a few nanometers across, made of semiconductor material, which has a “bandgap” between the energy levels of its electrons. When such materials gain energy from light shining on them, electrons can jump to a higher energy band; when they revert to their previous level, energy is released in the form of a photon, a particle of light. The frequency of this light, which determines its color, can be precisely tuned by selecting the shapes and dimensions of the dots. Besides display screens, quantum dots have potential for uses as solar cells, transistors, lasers, and quantum information devices.

The blinking phenomenon was first observed in the 1990s, soon after quantum dots were first made. “From that time on,” Bawendi says, “I would give presentations [about quantum dots], and people would say, ‘just make this go away!’ So, a lot of effort went into trying to eliminate it by engineering the interface between the dot and its environment, or by adding other molecules. But none of these things really worked well or were very reproducible.”

“We know that for some quantum information applications, we want a perfect single-photon emitter source,” Sun explains. But with currently available quantum dots, which otherwise might be well-suited to such applications, “they will turn on off randomly, and this is actually detrimental for any of the applications that utilize the photoluminescence from the dots.”

But now, she says, thanks to the team’s research, “we use these ultra-fast mid-infrared pulses, and the quantum dots can stay in the ‘on’ state. This can potentially be very useful for applications, like in quantum information science, where you really need a bright source of single photons without any intermittency.”

Similarly, for biomedical research applications, eliminating the blinking is essential, Shi says. “There are many biological processes that really require visualization with a steady photoluminescent tag, like tracking applications. For example, when we take medicines, you want to visualize how those drug molecules are being internalized in the cell, and where in the subcellular organelles it ends up.” This could lead to more efficient drug-discovery processes, he says, “but if the quantum dots start blinking a lot, you basically lose track of where the molecule is.”

Nelson, who is the Haslam and Dewey Professor of Chemistry, explains that the cause of the blinking phenomenon probably has to do with extra electrical charges, such as extra electrons, attaching to the outer part of the quantum dots, altering the surface properties so that there are other alternative pathways for the extra energy to be released instead of by emitting light.

“Various things can happen in a real environment,” Nelson says, “such that perhaps the quantum dot has an electron glommed onto it somewhere at the surface.” Instead of being electrically neutral, the quantum dot now has a net charge, and while it can still return to its ground state by emitting a photon, “the extra charge unfortunately also opens up a whole bunch of additional pathways for the electron’s excited state to return to the ground state without emitting a photon,” for example by shedding heat instead.

But when zapped with a burst of mid-infrared light, the extra charges tend to get knocked off the surface, allowing the quantum dots to produce stable emissions and stop their blinking.

It turns out, Utzat says, that this is “a very general process,” which might turn out to be useful for dealing with anomalous intermittency in some other devices, such as in so-called nitrogen vacancy centers in diamond, which are being harnessed for ultra-high-resolution microscopy and as sources of single-photons in optical quantum technologies. “Even though we have shown it for only one kind of workhorse material, the quantum dot, I believe that we can apply this method to other emitters,” he says. “I think the fundamental effect of using this mid-infrared light is applicable to a wide variety of different materials.”

Nelson says the effect also may not be limited to the mid-infrared pulses, which currently rely on bulky and expensive laboratory laser equipment and are not yet ready for commercial applications. The same principle could also extend to terahertz frequencies, he says, an area that has been under development in his lab and others and that in principle could lead to much smaller and less expensive devices.

The research team also included Ardavan Farahvash, Frank Gao, Zhuquan Zhang, Ulugbek Barotov, and Adam Willard, all at MIT. The work was supported by the U.S. Army Research Lab and the U.S. Army Research Office through the Institute for Soldier Nanotechnologies, the U.S. Department of Energy, and the Samsung Global Outreach Program.

This light-powered catalyst mimics photosynthesis

by Anne Trafton | MIT News Office |

By mimicking photosynthesis, the light-driven process that plants use to produce sugars, MIT researchers have designed a new type of photocatalyst that can absorb light and use it to drive a variety of chemical reactions.

The new type of catalyst, known as a biohybrid photocatalyst, contains a light-harvesting protein that absorbs light and transfers the energy to a metal-containing catalyst. This catalyst then uses the energy to perform reactions that could be useful for synthesizing pharmaceuticals or converting waste products into biofuels or other useful compounds.

“By replacing harmful conditions and reagents with light, photocatalysis can make pharmaceutical, agrochemical, and fuel synthesis more efficient and environmentally compatible,” says Gabriela Schlau-Cohen, an associate professor of chemistry at MIT and the senior author of the new study.

Working with colleagues at Princeton University and North Carolina State University, the researchers showed that the new photocatalyst could significantly boost the yield of the chemical reactions they tried. They also demonstrated that unlike existing photocatalysts, their new catalyst can absorb all wavelengths of light.

MIT graduate student Paul Cesana is the lead author of the paper, which appears today in the journal Chem.

High-energy reactions

Most catalysts speed up reactions by lowering the energy barrier needed for the reaction to occur. In the past 20 years or so, chemists have made great strides in developing photocatalysts — catalysts that can absorb energy from light. This allows them to catalyze reactions that couldn’t occur without that extra input of energy.

“In photocatalysis, the catalyst absorbs light energy to go to a much more highly excited electronic state. And through that energy, it introduces reactivity that would be prohibitively energy-intensive if all that were available were ground-state energy,” Schlau-Cohen says.

This is analogous to what plants do during photosynthesis. Plant cells’ photosynthetic machinery includes light-absorbing pigments such as chlorophyll that capture photons from sunlight. This energy is then transferred to other proteins that store the energy as ATP, and that energy is then used to produce carbohydrates.

In previous work on photocatalysts, researchers have used one molecule to perform both the light absorption and catalysis. This approach has limitations, because most of the catalysts used can only absorb certain wavelengths of light, and they don’t absorb light efficiently.

“When you have one molecule that needs to do the light harvesting and the catalysis, you can’t simultaneously optimize for both things,” Schlau-Cohen says. “It’s for that reason that natural systems separate them. In photosynthesis, there’s a dedicated architecture where some proteins do the light harvesting and then funnel that energy directly to the proteins that do the catalysis.”

To create their new biohybrid catalyst, the researchers decided to mimic photosynthesis and combine two separate elements: one to harvest light and another to catalyze the chemical reaction. For the light-harvesting component, they used a protein called R-phycoerythrin (RPE), found in red algae. They attached this protein to a ruthenium-containing catalyst, which has been previously used for photocatalysis on its own.

Working with North Carolina State University researchers led by professor of chemistry Felix Castellano, Schlau-Cohen’s lab showed that the light-harvesting protein could effectively capture light and transfer it to the catalyst. Then, Princeton University researchers led by David MacMillan, a professor of chemistry and a recent recipient of the Nobel Prize in chemistry, tested the performance of the catalyst in two different types of chemical reactions. One is a thiol-ene coupling, which joins a thiol and an alkene to form a thioether, and the other replaces a leftover thiol group with methyl after peptide coupling.

The Princeton team showed that the new biohybrid catalyst could boost the yield of these reactions up to tenfold, compared to the ruthenium photocatalyst on its own. They also found that the reactions could occur under illumination with red light, which has been difficult to achieve with existing photocatalysts and is beneficial because it produces fewer unwanted side reactions and is less damaging to tissue, so it could potentially be used in biological systems.

Chemical synthesis

This improved photocatalyst could be incorporated into chemical processes that use the two reactions tested in this study, the researchers say. Thiol-ene coupling is useful for creating compounds used in protein imaging and sensing, drug delivery, and biomolecule stability. As one example, it is used to synthesize lipopeptides that may enable easier uptake of antigen vaccine candidates. The other reaction the researchers tested, cysteinyl desulfurization, has many applications in peptide synthesis, including the production of enfurvitide, a drug that could be used to treat HIV.

This type of photocatalyst could also potentially be used to drive a reaction called lignin depolymerization, which could help to generate biofuels from wood or other plant materials that are difficult to break down.

The researchers now plan to try swapping in different light harvesting proteins and catalysts, to adapt their approach for a variety of chemical reactions.

“We did a proof of principle where you can separate light harvesting and catalytic function. Now we want to think about varying the catalytic piece and varying the light-harvesting piece to expand that toolkit, to see if this approach can work in different solvents and in different reactions,” Schlau-Cohen says.

This work was supported as part of the Bioinspired Light-Escalated Chemistry (BioLEC) Energy Frontier Research Center, funded by the U.S. Department of Energy Office of Science.

School of Science appoints 11 faculty members to named professorships

by School of Science |

The School of Science has announced that 11 faculty members have been appointed to named professorships. These positions offer additional support to professors to advance their research and develop their careers.

Andrew Babbin was named a Cecil and Ida Green Career Development Professor. A marine biogeochemist, Babbin studies the processes that return fixed nitrogen in the ocean back to nitrogen gas, exploring marine nitrogen’s control on life in the ocean and its effects on climate. His research sheds light on the ocean’s potential to sustain life and store carbon. Babbin earned a BS degree from Columbia University in 2008 and a PhD from Princeton University in 2014. He came to MIT in 2014 as a postdoc in the Department of Civil and Environmental Engineering before joining the Department of Earth, Atmospheric and Planetary Sciences in January 2017.

Gloria Choi was selected as the Mark Hyman Jr. Career Development Professor. Choi, an associate professor in the Department of Brain and Cognitive Sciences and an investigator with the Picower Institute, examines the interaction of the immune system with the brain and the effects of that interaction on neurodevelopment, behavior, and mood. She also studies how social behaviors are regulated according to sensory stimuli, context, internal state, and physiological status, and how these factors modulate neural circuit function via a combinatorial code of classic neuromodulators and immune-derived cytokines. She received her bachelor’s degree from the University of California at Berkeley, and her PhD from Caltech, where she studied with David Anderson. She was a postdoc in the laboratory of Richard Axel at Columbia University. Choi joined the MIT faculty as an assistant professor in 2013.

Arlene Fiore joined MIT as the inaugural Peter H. Stone and Paola Malanotte Stone Professor in Earth, Atmospheric and Planetary Sciences in July 2021. Her research encompasses air pollution, chemistry-climate connections, trends and variability in atmospheric constituents, and biosphere-atmosphere interactions. Fiore’s group investigates regional meteorology and climate feedbacks due to aerosols versus greenhouse gases, future air pollution responses to climate change, as well as the factors controlling the oxidizing capacity of the atmosphere. After earning a bachelor’s degree and PhD from Harvard University, Fiore held a research scientist position at the Geophysical Fluid Dynamics Laboratory and was appointed as an associate professor with tenure at Columbia University in 2011.

Peter H. Fisher is now the Thomas A. Frank (1977) Professor of Physics. His interests include the detection of dark matter, development of new particle detectors, compact energy supplies, and wireless energy transmission. Currently serving as the head of the Department of Physics, Fisher also holds appointments in the Institute for Soldier Nanotechnologies, the Laboratory for Nuclear Science, and the Kavli Institute. He is involved in CERN’s Alpha Magnetic Spectrometer experiment to make high-precision measurements of cosmic rays and the development of new ideas for dark matter. After receiving a BS in engineering physics from the University of California at Berkeley in 1983 and a PhD in nuclear physics from Caltech in 1988, Fisher was at the Johns Hopkins University from 1989 to 1994 and joined MIT in 1994.

Danna Freedman has been named the Frederick George Keyes Professor of Chemistry. Freedman leverages inorganic chemistry to solve problems in physics. Her research focuses on creating spin-based quantum bits and synthesizing new emergent materials. Freedman received her bachelor’s degree from Harvard University and her PhD from the University of California at Berkeley, then conducted postdoctoral research at MIT before joining the faculty at Northwestern University as an assistant professor in 2012, where she was promoted to associate professor in 2018 and full professor in 2020. Freedman returned to MIT’s Department of Chemistry in 2021.

Michel Goemans has been named the RSA Professor of Mathematics. Goemans has been head of the Department of Mathematics since July 1, 2018, following a year as interim head. He received his undergraduate degree in applied mathematics from Université Catholique de Louvain in 1987 and completed his PhD at MIT in 1990. He has been on the faculty since 1992, receiving tenure in 1999, and held the Leighton Family Professorship from 2007 to 2017. The RSA cryptosystem is the brainchild of Ron Rivest, Adi Shamir, and Len Adleman, whose fruitful collaboration spanned the Laboratory for Computer Science — today the Computer Science and Artificial Intelligence Laboratory (CSAIL) — and the Department of Mathematics. Goemans is also a member of the Theory of Computation Group of CSAIL, and recently joined the Computing Council of the MIT Schwarzman College of Computing. Goemans’ research interests include combinatorics, optimization and algorithms. In particular, his pioneering use of semidefinite optimization and other techniques for designing approximation algorithms for hard combinatorial optimization problems has been rewarded with several awards, such as the Fulkerson, Farkas and Dantzig prizes.

Or Hen was named the Class of 1956 Career Development Associate Professor of Physics. He investigates quantum chromodynamic effects in the nuclear medium and the interplay between partonic and nucleonic degrees of freedom in nuclei. Specifically, Hen utilizes high-energy scattering of electron, neutrino, photon, proton, and ion off atomic nuclei to study short-range correlations: temporal fluctuations of high-density, high-momentum, nucleon clusters in nuclei with important implications for nuclear, particle, atomic, and astrophysics. He received his undergraduate degree in physics and computer engineering from the Hebrew University and earned his PhD in experimental physics at Tel-Aviv University. Hen was an MIT Pappalardo Fellow in Physics from 2015 to 2017 before joining the physics faculty in July 2017.

Brett McGuire is now the Class of 1943 Career Development Assistant Professor of Chemistry. He uses the tools of physical chemistry, molecular spectroscopy, and observational astrophysics to understand how the chemical ingredients for life evolve with and help shape the formation of stars and planets. His group aims to detect more new molecules in space and to better understand their significance, advancing the field of astrochemistry. McGuire obtained a bachelor’s degree from the University of Illinois at Urbana-Champaign in 2009, a master’s degree from Emory University in 2011, and a PhD from Caltech in 2015. McGuire joined the Department of Chemistry in 2020.

Iain W. Stewart has been selected for the Otto (1939) and Jane Morningstar Professorship in Science. Stewart is a professor of physics and the director of the Center for Theoretical Physics. His research interests involve theoretical nuclear and particle physics. In particular, he focuses upon the development and application of effective field theories to answer fundamental questions about interactions between elementary particles. Stewart earned a bachelor’s degree in physics and mathematics and a master’s degree in physics from the University of Manitoba in Canada. He then received his PhD from Caltech in 1999. Stewart joined the physics faculty at MIT in 2003, was promoted to associate professor with tenure in 2009, and became a full professor in 2013.

Ankur Moitra, a theoretical computer scientist, is now the Norbert Wiener Professor of Mathematics. The aim of his work is to bridge the gap between theoretical computer science and machine learning by developing algorithms with provable guarantees and foundations for reasoning about their behavior. Moitra received his bachelor’s degree in electrical and computer engineering from Cornell University in 2007 and his master’s degree and PhD from MIT in computer science in 2009 and 2011, respectively, then spent two years as a fellow at the Institute for Advanced Study and Princeton University. Moitra returned to MIT in 2013 as a professor in applied mathematics and a principal investigator in CSAIL.

Seychelle M. Vos has been named a Robert A. Swanson (1969) Career Development Professor of Life Sciences. Vos examines the interplay of genome organization and gene expression to gain insight into how the organization of a cell affects what it becomes. Vos’ lab examines these pieces at a molecular scale using varied approaches from single-particle cryo-electron microscopy to X-ray crystallography, biochemistry to genetics. This work can help to build a biological understanding of diseases such as developmental disorders or cancers. She 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. Vos joined the Department of Biology in 2019.