Author: mantulin

Testing the waters

MIT sophomore Rachel Shen looks for microscopic solutions to big environmental challenges.

Lucy Jakub | Department of Biology
January 28, 2020

In 2010, the U.S. Army Corps of Engineers began restoring the Broad Meadows salt marsh in Quincy, Massachusetts. The marsh, which had grown over with invasive reeds and needed to be dredged, abutted the Broad Meadows Middle School, and its three-year transformation fascinated one inquisitive student. “I was always super curious about what sorts of things were going on there,” says Rachel Shen, who was in eighth grade when they finally finished the project. She’d spend hours watching birds in the marsh, and catching minnows by the beach.

In her bedroom at home, she kept an eye on four aquariums furnished with anubias, hornwort, guppy grass, amazon swords, and “too many snails.” Now, living in a dorm as a sophomore at MIT, she’s had to scale back to a single one-gallon tank. But as a Course 7 (Biology) major minoring in environmental and sustainability studies, she gets an even closer look at the natural world, seeing what most of us can’t: the impurities in our water, the matrices of plant cells, and the invisible processes that cycle nutrients in the oceans.

Shen’s love for nature has always been coupled with scientific inquiry. Growing up, she took part in Splash and Spark workshops for grade schoolers, taught by MIT students. “From a young age, I was always that kid catching bugs,” she says. In her junior year of high school, she landed the perfect summer internship through Boston University’s GROW program: studying ant brains at BU’s Traniello lab. Within a colony, ants with different morphological traits perform different jobs as workers, guards, and drones. To see how the brains of these castes might be wired differently, Shen dosed the ants with serotonin and dopamine and looked for differences in the ways the neurotransmitters altered the ants’ social behavior.

This experience in the Traniello lab later connected Shen to her first campus job working for MITx Biology, which develops online courses and educational resources for students with Department of Biology faculty. Darcy Gordon, one of the administrators for GROW and a postdoc at the Traniello Lab, joined MITx Biology as a digital learning fellow just as Shen was beginning her first year. MITx was looking for students to beta-test their biochemistry course, and Gordon encouraged Shen to apply. “I’d never taken a biochem course before, but I had enough background to pick it up,” says Shen, who is always willing to try something new. She went through the entire course, giving feedback on lesson clarity and writing practice problems.

Using what she learned on the job, she’s now the biochem leader on a student project with the It’s On Us Data Sciences club (formerly Project ORCA) to develop a live map of water contamination by rigging autonomous boats with pollution sensors. Environmental restoration has always been important to her, but it was on her trip to the Navajo Nation with her first-year advisory group, Terrascope, that Shen saw the effects of water scarcity and contamination firsthand. She and her peers devised filtration and collection methods to bring to the community, but she found the most valuable part of the project to be “working with the people, and coming up with solutions that incorporated their local culture and local politics.”

Through the Undergraduate Research Opportunities Program (UROP), Shen has put her problem-solving skills to work in the lab. Last summer, she interned at Draper and the Velásquez-García Group in MIT’s Microsystems Technologies Laboratories. Through experiments, she observed how plant cells can be coaxed with hormones to reinforce their cell walls with lignin and cellulose, becoming “woody” — insights that can be used in the development of biomaterials.

For her next UROP, she sought out a lab where she could work alongside a larger team, and was drawn to the people in the lab of Sallie “Penny” Chisholm in MIT’s departments of Biology and Civil and Environmental Engineering, who study the marine cyanobacterium Prochlorococcus. “I really feel like I could learn a lot from them,” Shen says. “They’re great at explaining things.”

Prochlorococcus is one of the most abundant photosynthesizers in the ocean. Cyanobacteria are mixotrophs, which means they get their energy from the sun through photosynthesis, but can also take up nutrients like carbon and nitrogen from their environment. One source of carbon and nitrogen is found in chitin, the insoluble biopolymer that crustaceans and other marine organisms use to build their shells and exoskeletons. Billions of tons of chitin are produced in the oceans every year, and nearly all of it is recycled back into carbon, nitrogen, and minerals by marine bacteria, allowing it to be used again.

Shen is investigating whether Prochlorococcus also recycles chitin, like its close relative Synechococcus that secretes enzymes which can break down the polymer. In the lab’s grow room, she tends to test tubes that glow green with cyanobacteria. She’ll introduce chitin to half of the cultures to see if specific genes in Prochlorococcus are expressed that might be implicated in chitin degradation, and identify those genes with RNA sequencing.

Shen says working with Prochlorococcus is exciting because it’s a case study in which the smallest cellular processes of a species can have huge effects in its ecosystem. Cracking the chitin cycle would have implications for humans, too. Biochemists have been trying to turn chitin into a biodegradable alternative to plastic. “One thing I want to get out of my science education is learning the basic science,” she says, “but it’s really important to me that it has direct applications.”

Something else Shen has realized at MIT is that, whatever she ends up doing with her degree, she wants her research to involve fieldwork that takes her out into nature — maybe even back to the marsh, to restore shorelines and waterways. As she puts it, “something that’s directly relevant to people.” But she’s keeping her options open. “Currently I’m just trying to explore pretty much everything.”

The new front against antibiotic resistance

Deborah Hung shares research strategies to combat tuberculosis as part of the Department of Biology's IAP seminar series on microbes in health and disease.

Lucy Jakub | Department of Biology
January 21, 2020

After Alexander Fleming discovered the antibiotic penicillin in 1928, spurring a “golden age” of drug development, many scientists thought infectious disease would become a horror of the past. But as antibiotics have been overprescribed and used without adhering to strict regimens, bacterial strains have evolved new defenses that render previously effective drugs useless. Tuberculosis, once held at bay, has surpassed HIV/AIDS as the leading cause of death from infectious disease worldwide. And research in the lab hasn’t caught up to the needs of the clinic. In recent years, the U.S. Food and Drug Administration has approved only one or two new antibiotics annually.

While these frustrations have led many scientists and drug developers to abandon the field, researchers are finally making breakthroughs in the discovery of new antibiotics. On Jan. 9, the Department of Biology hosted a talk by one of the chemical biologists who won’t quit: Deborah Hung, core member and co-director of the Infectious Disease and Microbiome Program at the Broad Institute of MIT and Harvard, and associate professor in the Department of Genetics at Harvard Medical School.

Each January during Independent Activities Period, the Department of Biology organizes a seminar series that highlights cutting-edge research in biology. Past series have included talks on synthetic and quantitative biology. This year’s theme is Microbes in Health and Disease. The team of student organizers, led by assistant professor of biology Omer Yilmaz, chose to explore our growing understanding of microbes as both pathogens and symbionts in the body. Hung’s presentation provided an invigorating introduction to the series.

“Deborah is an international pioneer in developing tools and discovering new biology on the interaction between hosts and pathogens,” Yilmaz says. “She’s done a lot of work on tuberculosis as well as other bacterial infections. So it’s a privilege for us to host her talk.”

A clinician as well as a chemical biologist, Hung understands firsthand the urgent need for new drugs. In her talk, she addressed the conventional approaches to finding new antibiotics, and why they’ve been failing scientists for decades.

“The rate of resistance is actually far outpacing our ability to discover new antibiotics,” she said. “I’m beginning to see patients [and] I have to tell them, I’m sorry, we have no antibiotics left.”

The way Hung sees it, there are two long-term goals in the fight against infectious disease. The first is to find a method that will greatly speed up the discovery of new antibiotics. The other is to think beyond antibiotics altogether, and find other ways to strengthen our bodies against intruders and increase patient survival.

Last year, in pursuit of the first goal, Hung spearheaded a multi-institutional collaboration to develop a new high-throughput screening method called PROSPECT (PRimary screening Of Strains to Prioritize Expanded Chemistry and Targets). By weakening the expression of genes essential to survival in the tuberculosis bacterium, researchers genetically engineered over 400 unique “hypomorphs,” vulnerable in different ways, that could be screened in large batches against tens of thousands of chemical compounds using PROSPECT.

With this approach, it’s possible to identify effective drug candidates 10 times faster than ever before. Some of the compounds Hung’s team has discovered, in addition to those that hit well-known targets like DNA gyrase and the cell wall, are able to kill tuberculosis in novel ways, such as disabling the bacterium’s molecular efflux pump.

But one of the challenges to antibiotic discovery is that the drugs that will kill a disease in a test tube won’t necessarily kill the disease in a patient. In order to address her second goal of strengthening our bodies against disease-causing microbes, Hung and her lab are now using zebrafish embryos to screen small molecules not just for their extermination of a pathogen, but for the survival of the host. This way, they can investigate drugs that have no effect on bacteria in a test tube but, in Hung’s words, “throw a wrench in the system” and interact with the host’s cells to provide immunity.

For much of the 20th century, microbes were primarily studied as agents of harm. But, more recent research into the microbiome — the trillions of organisms that inhabit our skin, gut, and cavities — has illuminated their complex and often symbiotic relationship with our immune system and bodily functions, which antibiotics can disrupt. The other three talks in the series, featuring researchers from Harvard Medical School, delve into the connections between the microbiome and colorectal cancer, inflammatory bowel disease, and stem cells.

“We’re just starting to scratch the surface of the dance between these different microbes, both good and bad, and their role in different aspects of organismal health, in terms of regeneration and other diseases such as cancer and infection,” Yilmaz says.

For those in the audience, these seminars are more than just a way to pass an afternoon during IAP. Hung addressed the audience as potential future collaborators, and she stressed that antibiotic research needs all hands on deck.

“It’s always a work in progress for us,” she said. “If any of you are very computationally-minded or really interested in looking at these large datasets of chemical-genetic interactions, come see me. We are always looking for new ideas and great minds who want to try to take this on.”

Whitehead Institute receives $10 million to study sex chromosomes’ impact on women’s health

Gift establishes the Brit Jepson d’Arbeloff Center on Women's Health.

Whitehead Institute
January 15, 2020

The Whitehead Institute has announced that Brit Jepson d’Arbeloff SM ’61 — a pioneering engineer, advocate for women in science, and philanthropic leader — has made a $10 million gift to support research uncovering the biological consequences of the sex chromosomes on women’s health and disease. The gift, one of the largest contributions ever made to the Whitehead Institute, will underwrite the establishment of the Brit Jepson d’Arbeloff Center on Women’s Health within the institute’s Sex Differences in Health and Disease Initiative.

The overall initiative is a comprehensive effort to understand sex differences at the molecular level — a long-neglected area of biomedical research — by building a fundamental understanding of how the female and male genome, transcriptome, epigenome, proteome, and metabolome differ. In the long run, determining the practical implications of those differences should lead to better, more effective treatments for both women and men.

The initiative holds particular promise for understanding health and treating disease in women. The d’Arbeloff Center is designed to drive progress toward that promise: catalyzing basic and translational research studies and collaborations that transform health care for women.

“Brit d’Arbeloff has been a trailblazer in science, research, and education,” says David C. Page, Whitehead Institute director and MIT professor of biology, who leads the sex differences initiative. “This is just the latest example of her determination to help drive biomedical research forward in significant ways. She is a staunch supporter of our work to understand the effects of the sex chromosomes on human health and disease, and her leadership and generosity have enabled us to build a solid research foundation.

“With this extraordinary new gift, she empowers us to build on that base by pursuing and translating discoveries that address the gaps in knowledge about health and disease in women,” Page says.

D’Arbeloff, a member of the Whitehead Institute’s board of directors since 2008, says, “I have long marveled at the stream of scientific discoveries and technical advances by Whitehead Institute researchers. For me, the most exciting of that work is being done within the sex differences initiative — exciting for both the imperative task it is taking on and the invaluable knowledge it is creating. The initiative will help to redress the longstanding inadequacy of research into women’s health and disease, and to catalyze development of therapeutics that are demonstrated effective for women.

“I believe that this is an essential biomedical quest, one as challenging today as the Human Genome Project was in 1991,” d’Arbeloff says. “No institution is better positioned to lead it than Whitehead Institute. And, in creating the Center for Women’s Health, I cannot make a more important investment in the health of my grandchildren and their children.”

D’Arbeloff is known for her enduring commitment to advancing biomedical research and to ensuring opportunities for women scientists and engineers. It is a commitment born of her own experience. She was the first woman to earn a mechanical engineering degree from Stanford University, graduating at the top of her class, but she had difficulty finding a job. When she earned a master’s degree at MIT in 1961, she was the sole woman in the school’s mechanical engineering department. She went on to become part of pioneering industries — contributing to the design of the Redstone missile in the 1960s, then programming software for Digital Equipment Corporation and Teradyne. For decades since, she has supported the efforts of women to succeed in science and engineering by offering her energy and leadership, her knowledge and experience, and her philanthropy.

While d’Arbeloff has provided substantial philanthropic support to a range of nonprofit organizations, she has had a particular impact in education, science, and technology. For example, beyond her decades of support for the Whitehead Institute, she established an MIT-based summer program to introduce female high school students to engineering careers, founded the Women in Science Committee of the Museum of Science, Boston, and supported the MGH Research Scholars Program to advance the careers of emerging clinical researchers.

The d’Arbeloff Center will create synergies and collaborations among Whitehead Institute investigators and facilities and those at biomedical research organizations throughout the Boston, Massachusetts region, across the nation, and around the world. Leveraging the knowledge gained by the initiative’s investigations into the molecular mechanisms through which the X and Y chromosomes give rise to sex-specific differences in cells, tissues, and organs, the center will delve into the ways that those differences contribute to conditions of health and of disease in women.

It will bring together experts in sex chromosome biology and sex hormones, computational biology and cutting-edge analytics, and proteomics, epigenetics, and metabolomics — fostering the kinds of researcher collaborations never before undertaken and spurring new approaches to the many-variable problem inherent in sex differences research. The center will also pursue partnerships to translate and develop meaningful discoveries into clinical applications for diagnosing, preventing, and treating disease in women. Ultimately, Page envisions, center-driven collaborations and partnerships will include university or medical school-based and independent research organizations, pharmaceutical and medical device manufacturers, and federal agencies.

Page, who will conclude his term as director in June, is also an investigator of the Howard Hughes Medical Institute. He has run a thriving research lab throughout his 35 years at Whitehead Institute, and is globally renowned for his groundbreaking research on sex chromosomes: His studies on the Y chromosome changed the way biomedical science views the function of sex chromosomes, and the work of his laboratory was cited twice in Science magazine’s “Top 10 Breakthroughs of the Year” — first for mapping a human chromosome and then for sequencing the human Y chromosome.

D’Arbeloff observes, “I have very concrete hopes for the center: I want it to help ensure that biomedical research reflects and benefits all of humanity — women and men, young and old. And I believe it is not hyperbole to say that David Page’s sex differences initiative truly has the potential to change the future of health care — for everyone.”

Bose grants for 2019 reward bold ideas across disciplines

Three innovative research projects in literature, plant epigenetics, and chemical engineering will be supported by Professor Amar G. Bose Research Grants.

MIT Resource Development
December 30, 2019

Now in its seventh year, the Professor Amar G. Bose Research Grants support visionary projects that represent intellectual curiosity and a pioneering spirit. Three MIT faculty members have each been awarded one of these prestigious awards for 2019 to pursue diverse questions in the humanities, biology, and engineering.

At a ceremony hosted by MIT President L. Rafael Reif on Nov. 25 and attended by past awardees, Provost Martin Schmidt, the Ray and Maria Stata Professor of Electrical Engineering and Computer Science, formally announced this year’s Amar G. Bose Research Fellows: Sandy Alexandre, Mary Gehring, and Kristala L.J. Prather.

The fellowships are named for the late Amar G. Bose ’51, SM ’52, ScD ’56, a longtime MIT faculty member and the founder of the Bose Corporation. Speaking at the event, President Reif expressed appreciation for the Bose Fellowships, which enable highly creative and unusual research in areas that can be hard to fund through traditional means. “We are tremendously grateful to the Bose family for providing the support that allows bold and curious thinkers at MIT to dream big, challenge themselves, and explore.”

Judith Bose, widow of Amar’s son, Vanu ’87, SM ’94, PhD ’99, congratulated the fellows on behalf of the Bose family. “We talk a lot at this event about the power of a great innovative idea, but I think it was a personal mission of Dr. Bose to nurture the ability, in each individual that he met along the way, to follow through — not just to have the great idea but the agency that comes with being able to pursue your idea, follow it through, and actually see where it leads,” Bose said. “And Vanu was the same way. That care that was epitomized by Dr. Bose not just in the idea itself, but in the personal investment, agency, and nurturing necessary to bring the idea to life — that care is a large part of what makes true change in the world.”

The relationship between literature and engineering

Many technological innovations have resulted from the influence of literature, one of the most notable being the World Wide Web. According to many sources, Sir Tim Berners-Lee, the web’s inventor, found inspiration from a short story by Arthur C. Clarke titled “Dial F for Frankenstein.” Science fiction has presaged a number of real-life technological innovations, including the defibrillator, noted in Mary Shelley’s “Frankenstein;” the submarine, described in Jules Verne’s “20,000 Leagues Under the Sea;” and earbuds, described in Ray Bradbury’s “Fahrenheit 451.” But the data about literature’s influence on STEM innovations are spotty, and these one-to-one relationships are not always clear-cut.

Sandy Alexandre, associate professor of literature, intends to change that by creating a large-scale database of the imaginary inventions found in literature. Alexandre’s project will enact the step-by-step mechanics of STEM innovation via one of its oft-unsung sources: literature. “To deny or sever the ties that bind STEM and literature is to suggest — rather disingenuously — that the ideas for many of the STEM devices that we know and love miraculously just came out of nowhere or from an elsewhere where literature isn’t considered relevant or at all,” she says.

During the first phase of her work, Alexandre will collaborate with students to enter into the database the imaginary inventions as they are described verbatim in a selection of books and other texts that fall under the category of speculative fiction—a category that includes but is not limited to the subgenres of fantasy, Afrofuturism, and science fiction. This first phase will, of course, require that students carefully read these texts in general, but also read for these imaginary inventions more specifically. Additionally, students with drawing skills will be tasked with interpreting the descriptions by illustrating them as two-dimensional images.

From this vast inventory of innovations, Alexandre, in consultation with students involved in the project, will decide on a short list of inventions that meet five criteria: they must be feasible, ethical, worthwhile, useful, and necessary. This vetting process, which constitutes the second phase of the project, is guided by a very important question: what can creating and thinking with a vast database of speculative fiction’s imaginary inventions teach us about what kinds of ideas we should (and shouldn’t) attempt to make into a reality? For the third and final phase, Alexandre will convene a team to build a real-life prototype of one of the imaginary inventions. She envisions this prototype being placed on exhibit at the MIT Museum.

The Bose research grant, Alexandre says, will allow her to take this project from a thought experiment to lab experiment. “This project aims to ensure that literature no longer play an overlooked role in STEM innovations. Therefore, the STEM innovation, which will be the culminating prototype of this research project, will cite a work of literature as the main source of information used in its invention.”

Nature’s role in chemical production

Kristala L.J. Prather ’94, the Arthur D. Little Professor of Chemical Engineering, has been focused on using biological systems for chemical production during the 15 years she’s been at the Institute. Biology as a medium for chemical synthesis has been successfully exploited to commercially produce molecules for uses that range from food to pharmaceuticals — ethanol is a good example. However, there is a range of other molecules with which scientists have been trying to work, but they have faced challenges around an insufficient amount of material being produced and a lack of defined steps needed to make a specific compound.

Prather’s research is rooted in the fact that there are a number of naturally (and unnaturally) occurring chemical compounds in the environment, and cells have evolved to be able to consume them. These cells have evolved or developed a protein that will sense a compound’s presence — a biosensor — and in response will make other proteins that help the cells utilize that compound for its benefit.

“We know biology can do this,” Prather says, “so if we can put together a sufficiently diverse set of microorganisms, can we just let nature make these regulatory molecules for anything that we want to be able to sense or detect?” Her hypothesis is that if her team exposes cells to a new compound for a long enough period of time, the cells will evolve the ability to either utilize that carbon source or develop an ability to respond to it. If Prather and her team can then identify the protein that’s now recognizing what that new compound is, they can isolate it and use it to improve the production of that compound in other systems. “The idea is to let nature evolve specificity for particular molecules that we’re interested in,” she adds.

Prather’s lab has been working with biosensors for some time, but her team has been limited to sensors that are already well characterized and that were readily available. She’s interested in how they can get access to a wider range of what she knows nature has available through the incremental exposure of new compounds to a more comprehensive subset of microorganisms.

“To accelerate the transformation of the chemical industry, we must find a way to create better biological catalysts and to create new tools when the existing ones are insufficient,” Prather says. “I am grateful to the Bose Fellowship Committee for allowing me to explore this novel idea.”

Prather’s findings as a result of this project hold the possibility of broad impacts in the field of metabolic engineering, including the development of microbial systems that can be engineered to enhance degradation of both toxic and nontoxic waste.

Adopting orphan crops to adapt to climate change

In the context of increased environmental pressure and competing land uses, meeting global food security needs is a pressing challenge. Although yield gains in staple grains such as rice, wheat, and corn have been high over the last 50 years, these have been accompanied by a homogenization of the global food supply; only 50 crops provide 90% of global food needs.

However, there are at least 3,000 plants that can be grown and consumed by humans, and many of these species thrive in marginal soils, at high temperatures, and with little rainfall. These “orphan” crops are important food sources for farmers in less developed countries but have been the subject of little research.

Mary Gehring, associate professor of biology at MIT, seeks to bring orphan crops into the molecular age through epigenetic engineering. She is working to promote hybridization, increase genetic diversity, and reveal desired traits for two orphan seed crops: an oilseed crop, Camelina sativa (false flax), and a high-protein legume, Cajanus cajan (pigeon pea).

C. sativa, which produces seeds with potential for uses in food and biofuel applications, can grow on land with low rainfall, requires minimal fertilizer inputs, and is resistant to several common plant pathogens. Until the mid-20th century, C. sativa was widely grown in Europe but was supplanted by canola, with a resulting loss of genetic diversity. Gehring proposes to recover this genetic diversity by creating and characterizing hybrids between C. sativa and wild relatives that have increased genetic diversity.

“To find the best cultivars of orphan crops that will withstand ever increasing environmental insults requires a deeper understanding of the diversity present within these species. We need to expand the plants we rely on for our food supply if we want to continue to thrive in the future,” says Gehring. “Studying orphan crops represents a significant step in that direction. The Bose grant will allow my lab to focus on this historically neglected but vitally important field.”

Building a platform to image membrane proteins

Biologists devise an efficient method to prepare fluorescently tagged proteins and simulate their native environment.

Raleigh McElvery | Department of Biology
December 18, 2019

All cells have a lipid membrane that encircles their internal components — forming a protective barrier to control what gets in and what stays out. The proteins embedded in these membranes are essential for life; they help facilitate nutrient transport, energy conversion and storage, and cellular communication. They are also important in human disease, and represent around 60 percent of approved drug targets. In order to study these membrane proteins outside the complexity of the cell, researchers must use detergent to strip away the membrane and extract them. However, determining the best detergent for each protein can involve extensive trial and error. And, removing a protein from its natural environment risks destabilizing the folded structure and disrupting function.

In a study published on Dec. 9 in Cell Chemical Biology, scientists from MIT devised a rapid and generalizable way to extract, purify, and label membrane proteins for imaging without any detergent at all — bringing along a portion of the surrounding membrane to protect the protein and simulate its natural environment. Their approach combines well-established chemical and biochemical techniques in a new way, efficiently isolating the protein so it can be fluorescently labeled and examined under a microscope.

“I always joke that it’s not very lifelike to study proteins in soap,” says senior author Barbara Imperiali, a professor of biology and chemistry. “We’ve created a workflow that allows membrane proteins to be imaged while maintaining their native identities and interactions. Hopefully now fewer people will shy away from studying membrane proteins, given their importance in many physiological processes.”

As a member of the Imperiali lab, former postdoc and lead author Jean-Marie Swiecicki investigated membrane proteins from the foodborne pathogen Campylobacter jejuni. In this study, Swiecicki focused on PglC and PglA, two membrane proteins that play a role in enabling the bacteria to infect human cells. His experiments required labeling PglC and PglA with fluorescent tags in order to track them. However, he wasn’t satisfied with existing methods to do so.

In some cases, the fluorescent tags that must be incorporated into the protein in order to visualize it are too large to be placed at defined positions. In other cases, these tags don’t shine brightly enough, or interfere with the structure and function of the protein.

To avoid such issues, Swiecicki decided to use a method known as “unnatural amino-acid mutagenesis.” Amino acids are the units that compose the protein, and unnatural amino-acid mutagenesis involves adding a new amino acid containing an engineered chemical group within the protein sequence. This chemical group can then be labeled with a brightly glowing tag.

Swiecicki inserted the genetic code for the C. jejuni membrane proteins into a different bacterium, Escherichia coli. Inside E. coli, he could incorporate the unnatural amino acid, which could be chemically modified to add the fluorescent label.

When it came time to remove the proteins from the membrane, he substituted a different substance for the detergent: a polymer of styrene-maleic acid (SMA). Unlike detergent, SMA wraps the extracted protein and a small segment of the associated membrane in a protective shell, preserving its native environment. Imperiali explains, “It’s like a scarf protecting your neck from the cold.”

Swiecicki could then monitor the glowing proteins under a microscope to verify his technique was selective enough to isolate individual membrane proteins. The entire process, he says, takes just a few days, and is generally much faster and more reliable than detergent-based extraction methods, which can take months and require the expertise of highly-trained biochemists to optimize.

“I wouldn’t say it’s a magic bullet that’s going to work for every single protein,” he says. “But it’s a highly efficient tool that could make it easier to study many different kinds of membrane proteins.” Eventually, he says, it may even help facilitate high throughput drug screens.

“As someone who works on membrane protein complexes, I can attest to the great need for better methods to study them,” says Suzanne Walker, a professor of microbiology at Harvard Medical School who was not involved in the study. She hopes to extend the approach outlined in the paper to the protein complexes she investigates in her own lab. “I appreciated the extensive detail included in the text about how to apply the strategy successfully,” she adds.

The next steps will be testing the technique on mammalian proteins, and isolating multiple proteins at once in the SMA shell to observe their interactions. And, of course, every new technique deserves a name. “We’re still working on a catchy acronym,” Imperiali says. “Any ideas?”

This research was funded by the Jane Coffin Childs Memorial Fund for Medical Research, Philippe Foundation, and National Institutes of Health.

Hazel Sive named dean of Northeastern University College of Science

Professor and Whitehead Institute member has conducted wide-ranging research in vertebrate developmental biology.

Whitehead Institute
December 16, 2019

Hazel Sive, a globally respected developmental biologist and educator, will become dean of the Northeastern University College of Science, beginning in June 2020. Sive, a member of the Whitehead Institute who has also been on the faculty of the MIT Department of Biology since 1991, is a much-lauded teacher and academic leader at MIT.

“The greatest professional honor of my life has been to be a member of Whitehead Institute and a professor of biology at MIT. To be part of the extraordinary research landscape, to educate our outstanding MIT students, and to have had opportunities to contribute to governance and international activities, has been quite wonderful,” says Sive.

“At the same time, this is an exciting next step in my career,” Sive says. “Northeastern has a fantastic, innovative ethos that meshes with my deep interest in the future of higher education. I look forward to leading the Northeastern College of Science toward even greater excellence in research and education.”

“Hazel has long been committed to teaching and academic leadership, and Northeastern will benefit from her broad experience and expertise,” says David C. Page, Whitehead Institute director and member. “Although we will miss her wit, energy, incisive intelligence, and passionate commitment to outstanding science research, we congratulate her on this wonderful new endeavor.”

Sive, who is also an associate member of Broad Institute of MIT and Harvard, is recognized for her groundbreaking research in vertebrate developmental biology. Her contributions have been wide-ranging, encompassing molecular definition of anterior position, development of the brain ventricular system, and identifying novel cell biological processes, including “epithelial relaxation” and “basal constriction.” Her group defined the extreme anterior domain that gives rise to the mouth and that is a crucial craniofacial signaling center. Sive developed the zebrafish as a tool to analyze human neurodevelopmental disorders, most recently focusing on the metabolic underpinnings of disorders such as autism and 16p11.2 deletion syndrome. She has also been a pioneer in use of the frog Xenopus and zebrafish model systems; indeed, she created the Cold Spring Harbor Laboratory Course on Early Development of Xenopus — which has run for more than 25 years — and she is editor-in-chief of a new two-volume “Xenopus Lab Manual.”

A highly effective educator, Sive has been named a MacVicar Faculty Fellow — MIT’s highest undergraduate teaching accolade — and has twice received the MIT School of Science Teaching Prize. She has taught the undergraduate introductory biology course for 18 years; co-teaches the graduate developmental neuroscience course; and recently created the innovative course Building with Cells for undergraduate and graduate students.

Among her myriad leadership roles, Sive chaired the MIT biology department undergraduate program and has chaired an array of faculty committees. She was the first associate dean of science — where she led the school’s education strategy, promoted diversity in graduate student and faculty recruitment, and devised programs for postdoctoral and junior faculty training. Notably, in 2011 Sive initiated the groundbreaking “Report on the Status of Women Faculty in Science at MIT”.

A native of South Africa — where she earned bachelor’s degrees in chemistry and zoology from the University of Witwatersrand, Johannesburg — Sive has engaged in building connections between MIT and Africa. In 2014, Sive founded the MIT-Africa Initiative, where she serves as faculty director. With the tagline “Collaborating for Impact,” MIT-Africa promotes mutually beneficial engagements in research, education, and innovation. She is founder and faculty director of MISTI-Africa Internships, sending students to multiple African countries. Sive has also focused globally on education, and is founding director of higher education for the MIT Abdul Latif Jameel World Education Lab (J-WEL), located in the Office of Open Learning, started in 2017, that promotes excellence in education across the world. From her leadership, J-WEL Higher Education has built a strong membership across five continents.

Mary Gehring: Using flowering plants to explore epigenetic inheritance

Biologist’s studies illuminate a control system that influences how traits are passed along to new generations.

Anne Trafton | MIT News Office
December 16, 2019

Genes passed down from generation to generation play a significant role in determining the traits of every organism. In recent decades, scientists have discovered that another layer of control, known as epigenetics, is also critically important in shaping those characteristics.

Those added controls often work through chemical modifications of genes or other sections of DNA, which influence how easily those genes can be expressed by a cell. Many of those modifications are similar across species, allowing scientists to use plants as an experimental model to uncover how epigenetic processes work.

“Many of the epigenetic phenomena we know about were first discovered in plants, and in terms of understanding the molecular mechanisms, work on plants has also led the way,” says Mary Gehring, an associate professor of biology and a member of MIT’s Whitehead Institute for Biomedical Research.

Gehring’s studies of the small flowering plant Arabidopsis thaliana have revealed many of the mechanisms that underlie epigenetic control, shedding light on how these modifications can be passed from generation to generation.

“We’re trying to understand how epigenetic information is used during plant growth and development, and looking at the dynamics of epigenetic information through development within a single generation, between generations, and on an evolutionary timescale,” she says.

Seeds of discovery

Gehring, who grew up in a rural area of northern Michigan, became interested in plant biology as a student at Williams College, where she had followed her older sister. During her junior year at Williams, she took a class in plant growth and development and ended up working in the lab of the professor who taught the course. There, she studied how development of Arabidopsis is influenced by plant hormones called auxins.

After graduation, Gehring went to work for an environmental consulting company near Washington, but she soon decided that she wanted to go to graduate school to continue studying plant biology. She enrolled at the University of California at Berkeley, where she joined a lab that was studying how different genetic mutations affect the development of seeds.

That lab, led by Robert Fischer, was one of the first to discover an epigenetic phenomenon called gene imprinting in plants. Gene imprinting occurs when an organism expresses only the maternal or paternal version of particular gene. This phenomenon has been seen in flowering plants and mammals.

Gehring’s task was to try to figure out the mechanism behind this phenomenon, focusing on an Arabidopsis imprinted gene called MEDEA. She found that this type of imprinting is achieved by DNA demethylation, a process of removing chemical modifications from the maternal version of the gene, effectively turning it on.

After finishing her PhD in 2005, she worked as a postdoc at the Fred Hutchinson Cancer Research Center, in the lab of Steven Henikoff. There, she began doing larger, genome-scale studies in which she could examine epigenetic markers for many genes at once, instead of one at a time.

During that time, she began studying some of the topics she continues to investigate now, including regulation of the enzymes that control DNA methylation, as well as regulation of “transposable elements.” Also known as “jumping genes,” these sequences of DNA can change their position within the genome, sometimes to promote their own expression at the expense of the organism. Cells often use methylation to silence these genes if they generate harmful mutations.

Patterns of inheritance

After her postdoc, Gehring was drawn to MIT by “how passionate people are about what they’re working on, whether that’s biology or another subject.”

“Boston, especially MIT and Whitehead, is a great environment for science,” she says. “It seemed like there were a lot of opportunities to get really smart and talented students in the lab and have interesting colleagues to talk with.”

When Gehring joined the Whitehead Institute in 2010, she was the only plant biologist on the faculty, but she has since been joined by Associate Professor Jing-Ke Weng.

Her lab now focuses primarily on questions such as how maternal and paternal parents contribute to reproduction, and how their differing interests can lead to genetic conflicts. Gene imprinting is one way that this conflict is played out. Gehring has also discovered that small noncoding RNA molecules play an important role in imprinting and other aspects of inheritance by directing epigenetic modifications such as DNA methylation.

“One thing we’ve found is that this noncoding RNA pathway seems to control the transcriptional dosage of seeds, that is, how many of the transcripts are from the maternally inherited genome and how many from the paternally inherited genome. Not just for imprinted genes, but also more broadly for genes that aren’t imprinted,” Gehring says.

She has also identified a genetic circuit that controls an enzyme that is required to help patterns of DNA methylation get passed from parent to offspring. When this circuit is disrupted, the methylation state changes and unusual traits can appear. In one case, she found that the plants’ leaves become curled after a few generations of disrupted methylation.

“You need this genetic circuit in order to maintain stable methylation patterns. If you don’t, then what you start to see is that the plants develop some phenotypes that get worse over generational time,” she says.

Many of the epigenetic phenomena that Gehring studies in plants are similar to those seen in animals, including humans. Because of those similarities, plant biology has made significant contributions to scientists’ understanding of epigenetics. The phenomenon of epigenomic imprinting was first discovered in plants, in the 1970s, and many other epigenetic phenomena first seen in plants have also been found in mammals, although the molecular details often vary.

“There are a lot of similarities among epigenetic control in flowering plants and mammals, and fungi as well,” Gehring says. “Some of the pathways are plant-specific, like the noncoding RNA pathway that we study, where small noncoding RNAs direct DNA methylation, but small RNAs directing silencing via chromatin is something that happens in many other systems as well.”

A new way to regulate gene expression

Biologists uncover an evolutionary trick to control gene expression that reverses the flow of genetic information from RNA splicing back to transcription.

Raleigh McElvery | Department of Biology
December 9, 2019

Sometimes, unexpected research results are simply due to experimental error. Other times, it’s the opposite — the scientists have uncovered a new phenomenon that reveals an even more accurate portrayal of our bodies and our universe, overturning well-established assumptions. Indeed, many great biological discoveries are made when results defy expectation.

A few years ago, researchers in the Burge lab were comparing the genomic evolution of several different mammals when they noticed a strange pattern. Whenever a new nucleotide sequence appeared in the RNA of one lineage, there was generally an increase in the total amount of RNA produced from the gene in that lineage. Now, in a new paper, the Burge lab finally has an explanation, which redefines our understanding of how genes are expressed.

Once DNA is transcribed into RNA, the RNA transcript must be processed before it can be translated into proteins or go on to serve other roles within the cell. One important component of this processing is splicing, during which certain nucleotide sequences (introns) are removed from the newlymade RNA transcript, while others (the exons) remain. Depending on how the RNA is spliced, a single gene can give rise to a diverse array of transcripts.

Given this order of operations, it makes sense that transcription affects splicing. After all, splicing cannot occur without an RNA transcript. But the inverse theory — that splicing can affect transcription — is now gaining traction. In a recent study, the Burge lab showed that splicing in an exon near the beginning of a gene impacts transcription and increases gene expression, offering an explanation for the patterns in their previous findings.

“Rather than Step A impacting Step B, what we found here is that Step B, splicing, actually feeds back to influence Step A, transcription,” says Christopher Burge, senior author and professor of biology. “It seems contradictory, since splicing requires transcription, but there is actually no contradiction if — as in our model — the splicing of one transcript from a gene influences the transcription of subsequent transcripts from the same gene.”

The study, published on Nov. 28 in Cell, was led by Burge lab postdoc Ana Fiszbein.

Promoting gene expression

In order for transcription to begin, molecular machines must be recruited to a special sequence of DNA, known as the promoter. Some promoters are better at recruiting this machinery than others, and therefore initiate transcription more often. However, having different promoters available to produce slightly different transcripts from a gene helps boost expression and generates transcript diversity, even before splicing occurs mere seconds or minutes later. ​

At first, Fiszbein wasn’t sure how the new exons were enhancing gene expression, but she theorized that new promoters were involved. Based on evolutionary data available and her experiments at the lab bench, she could see that wherever there was a new exon, there was usually a new promoter nearby. When the exon was spliced in, the new promoter became more active.

The researchers named this phenomenon “exon-mediated activation of transcription starts” (EMATS). They propose a model in which the splicing machinery associated with the new exon recruits transcription machinery to the vicinity, activating transcription from nearby promoters. This process, the researchers predict, likely helps to regulate thousands of mammalian genes across species.

A more flexible genome

Fiszbein believes that EMATS has increased genome complexity over the course of evolution, and may have contributed to species-specific differences. For instance, the mouse and rat genomes are quite similar, but EMATS could have helped produce new promoters, leading to regulatory changes that drive differences in structure and function between the two. EMATS may also contribute to differences in expression between tissues in the same organism.

“EMATS adds a new layer of complexity to gene expression regulation,” Fiszbein says. “It gives the genome more flexibility, and introduces the potential to alter the amount of RNA produced.”

Juan Valcárcel, a research professor at the Catalan Institution for Research and Advanced Studies in the Center for Genomic Regulation in Barcelona, Spain, says understanding the mechanisms behind EMATS could also have biotechnological and therapeutic implications. “A number of human conditions, including genetic diseases and cancer, are caused by a defect or an excess of particular genes,” he says. “Reverting these anomalies through modulation of EMATS might provide innovative therapies.”

Researchers have already begun to tinker with splicing to control transcription. According to Burge, pharmaceutical companies like Ionis, Novartis, and Roche are concocting drugs to regulate splicing and treat diseases like spinal muscular atrophy. There are many ways to decrease gene expression, but it’s much harder to increase it in a targeted manner. “Tweaking splicing might be one way to do that,” he says.

“We found a way in which our cells change gene expression,” Fiszbein adds. “And we can use that to manipulate transcript levels as we want. I think that’s the most exciting part.”

This research was funded by the National Institutes of Health and the Pew Latin American Fellows Program in the Biomedical Sciences.

Three MIT seniors to join 2021 class of Schwarzman Scholars

Two alumni have also been selected; the scholars will study global affairs at Beijing’s Tsinghua University.

Julia Mongo | Distinguished Fellowships
December 4, 2019

Three MIT seniors, Mariam Dogar, Adedoyin Olateru-Olagbegi, and Jessica Quaye, and alumna Jessica Wang ’16, MEng ’17 are recipients of this year’s Schwarzman Scholarship distinguished fellowship. Another alumna was also awarded a scholarship but is waiting to make a public announcement until she has shared the news with her employer.

The five winners were selected from an applicant of pool over 4,700 candidates and will join fellow Schwarzman Scholars from around the world in China next August. Scholars complete a one-year master’s degree in global affairs at Beijing’s Tsinghua University. Their education is complemented by internships, career development mentors, high-profile speakers, and opportunities to travel throughout China.

Inspired by the Rhodes Scholarship, the Schwarzman Scholarship program began in 2015 to bring together talented young leaders and prepare them for the geopolitical and economic challenges of the 21st century by deepening their understanding of China. Since its inception, 18 MIT students and alumni have been named Schwarzman Scholars.

Kim Benard, assistant dean of distinguished fellowships in Career Advising and Professional Development prepares MIT’s applicants, with assistance from the Presidential Committee on Distinguished Fellowships’ faculty members. MIT students and recent alumni interested in learning more about the Schwarzman Scholarship program should contact fellowships@mit.edu.

Hailing from Northborough, Massachusetts, Mariam Dogar is majoring in biology and minoring in urban studies and planning. She aims to make health care more accessible and equitable through reworking outdated policies and utilizing technology. Dogar has worked at the World Bank developing telemedicine policy recommendations for lower middle-income countries. She has two years of experience on the teaching team of MIT’s negotiation and leadership classes, where she shaped pedagogy and co-taught a workshop for MBA students in Malaysia. She has taught humanitarian design in Greece with MIT D-Lab, worked in digital health care investing in the Middle East, and volunteered in refugee programs in Jordan. She is a co-president of MIT Mock Trial and GlobeMed@MIT. She is also an executive member of PaksMIT and counselor for Camp Kesem.

Jessica Quaye, an electrical engineering and computer science major, has conducted research with MIT.nano and the HCIE group in CSAIL. She has also sharpened her technical and business management skills through internships at Google, Microsoft, and Bain and Company. Quaye, a Tau Beta Pi Scholar, is president of the MIT African Students’ Association. She serves on MIT’s Undergraduate Association committees and the EECS Undergraduate Student Advisory Group. She founded the International Students of Color Working Group to support the needs of first-year international students, and she established the first MIT Global Teaching Lab initiative in Ghana. Quaye is from Accra, Ghana. As a Schwarzman Scholar, she hopes to deepen her understanding of public policy and dreams of one day driving policy change in Ghana.

Adedoyin Olateru-Olagbegi, from Hanover, Maryland, is majoring in computer science, economics, and data science. She envisions a world where quality health care is accessible to all, and plans to focus on health in developing countries with an emphasis on innovative digital tools. She has explored her interests in development and public health through classes that have taken her to South Africa and Colombia. As director of Camp Kesem at MIT, Olateru-Olagbegi organizes an annual summer camp for children affected by a parent’s cancer and oversees the MIT students who work with them. She has also held leadership roles with MIT Emergency Medical Services, the MIT Black Students’ Union, and Sigma Kappa Sorority, and has served on several MIT Institute Committees, including as a student advisor to President L. Rafael Reif.

Jessica Wang graduated from MIT in 2016 with a Bachelor of Science in computer science and engineering and received a Master of Engineering in 2017. She is passionate about utilizing technology for good and bringing her joint engineering and design background to shape technology policy. She currently lives in San Francisco, where she builds collaborative design software at Figma. She works on diversity and inclusion initiatives in the workplace and volunteers with Larkin Street, a nonprofit serving homeless youth, as a YCore Fellow. In the past, she’s worked at a machine learning startup, Facebook, and Uber. At MIT, Wang researched online sociopolitical discourse and misinformation, writing her thesis on digital systems to bridge ideological divides. She served as president of MIT Chinese Students’ Club and held leadership positions in MIT TechX and HackMIT.

Six MIT faculty elected 2019 AAAS Fellows

Baggereroer, Flynn, Harris, Klopfer, Lauffenburger, and Leonard are recognized for their efforts to advance science.

MIT News Office
November 26, 2019

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

The new fellows are among a group of 443 AAAS members elected by their peers in recognition of their scientifically or socially distinguished efforts to advance science. This year’s fellows will be honored at a ceremony on Feb. 15, at the AAAS Annual Meeting in Seattle.

Arthur B. Baggeroer is a professor of mechanical, ocean and electrical engineering, the Ford Professor of Engineering, Emeritus, and an international authority on underwater acoustics. Throughout his career he made significant advances to geophysical signal processing and sonar technology, in addition to serving as a long-time intellectual resource to the U.S. Navy.

Suzanne Flynn is a professor of linguistics and language acquisition, and a leading researcher on the acquisition of various aspects of syntax by children and adults in bilingual, second- and third-language contexts. She also works on the neural representation of the multilingual brain and issues related to language impairment, autism, and aging. Flynn is currently editor-in-chief and a co-founding editor of Syntax: A Journal of Theoretical, Experimental and Interdisciplinary Research.

Wesley L. Harris is the Charles Stark Draper Professor of Aeronautics and Astronautics and has served as MIT associate provost and head of the Department of Aeronautics and Astronautics. His academic research program includes unsteady aerodynamics, aeroacoustics, rarefied gas dynamics, sustainment of capital assets, and chaos in sickle cell disease. Prior to coming to MIT, he was a NASA associate administrator, responsible for all programs, facilities, and personnel in aeronautics.

Eric Klopfer is a professor and head of the Comparative Media Studies/Writing program and the director of the Scheller Teacher Education Program and The Education Arcade at MIT. His interests range from the design and development of new technologies for learning to professional development and implementation in schools. Much of Klopfer’s research has focused on computer games and simulations for building understanding of science, technology, engineering, and mathematics.

Douglas Lauffenburger, is the Ford Professor of Biological Engineering, Chemical Engineering, and Biology, and head of the Department of Biological Engineering. He and his research group investigate the interface of bioengineering, quantitative cell biology, and systems biology. The lab’s main focus has been on fundamental aspects of cell dysregulation, complemented by translational efforts in identifying and testing new therapeutic ideas.

John J. Leonard is the Samuel C. Collins Professor of Mechanical and Ocean Engineering and a leading expert in navigation and mapping for autonomous mobile robots. His research focuses on long-term visual simultaneous localization and mapping in dynamic environments. In addition to underwater vehicles, Leonard has applied his pursuit of persistent autonomy to the development of self-driving cars.

This year’s fellows will be formally announced in the AAAS News and Notes section of Science on Nov. 28.