Author: mantulin

Three MIT biologists receive NIH Outstanding Investigator Awards

Graham Walker, Michael Yaffe, and Robert Weinberg earn support from the National Institutes of Health to further their research endeavors.

Raleigh McElvery | Department of Biology
September 19, 2017

This fall, two faculty members from the MIT Department of Biology received R35 Outstanding Investigator Awards sponsored by the National Institute of Environmental Health Sciences (NIEHS), while a third garnered the same distinction from the National Cancer Institute (NCI). These awards provide long-term support to experienced investigators with outstanding records of research productivity as they undertake lengthy projects with unusual potential.

Graham Walker, the American Cancer Society Professor in the Department of Biology at MIT, a member of the Center for Environmental Health Sciences, and affiliate member of the Koch Institute for Integrative Cancer Research, is one of two biology faculty to earn the R35 Outstanding Investigator Award from the NIEHS.

This award is supported by the NIEHS through the Revolutionizing Innovative, Visionary Environmental health Research (RIVER) program. The program recognizes outstanding investigators in the field of environmental health, potentially offering up to $750,000 per year over the next eight years.

The awardees include both mid-career and senior researchers, whose work spans many aspects environmental health science — including technology development, mechanistic, clinical, and epidemiological research. A total of eight investigators received the NIEHS RIVER R35 this year.

“The RIVER program is designed to fund people, not projects,” said David Balshaw, chief of the NIEHS Exposure, Response, and Technology Branch who leads the NIEHS team overseeing this initiative. “It gives outstanding environmental health scientists stable funding, time, and, importantly, flexibility to pursue creative scientific ideas, rather than constantly writing grants to support their research programs.”

Walker will use his award to continue investigating the fundamental mechanisms of mutagenesis and DNA repair, with a special emphasis on the Rev1/3/7-dependent pathway of mutagenic translation synthesis found in eukaryotes, including humans. He and his colleagues recently published evidence suggesting that inhibiting this pathway could potentially improve chemotherapy.

Michael Yaffe, the David H. Koch Professor of Science at MIT, a member of the Koch Institute and the Center for Environmental Health Sciences, and attending surgeon at the Beth Israel Deaconess Medical Center, also received a NIEHS RIVER R35 award.

Yaffe’s work concerns how cells respond to injury, including damage to DNA and RNA molecules arising because of the environment and in response to drugs used to treat cancer. He is also interested in the relationship between inflammation, blood clotting, and cancer. He employs multidisciplinary approaches harnessing techniques from biochemistry, structural and cell biology, computer science, and systems biology/engineering.

Yaffe will use his funds to further a project investigating the roles of protein kinases in coordinating cellular responses to damage to both DNA and RNA molecules.

Robert Weinberg, founding member of the Whitehead Institute, professor of biology at MIT, an affiliate member of the Koch Institute, and director of the MIT Ludwig Center for Molecular Oncology, has received his R35 Outstanding Investigator Award from the NCI.

The award provides up to $600,000 per year over seven years to accomplished cancer researchers, nominated by their institutions, who have served as principal investigators on an NCI grant for the last five years. A total of 18 investigators received the NCI Outstanding Investigator Award this year.

“The NCI Outstanding Investigator Award addresses a problem that many cancer researchers experience: finding a balance between focusing on their science while ensuring that they will have funds to continue their research in the future,” said Dinah Singer, director of NCI’s Division of Cancer Biology. “With seven years of uninterrupted funding, NCI is providing investigators the opportunity to fully develop exceptional and ambitious cancer research programs.”

Weinberg is a pioneer in cancer research, best known for his role in discovering the first human oncogene — a gene that, when activated, can spur tumor growth. His lab is also credited with isolating the first known tumor suppressor gene.

He will use his funds to delve into the mechanisms of metastasis — the process that allows cancer cells to spread. He aims to learn more about how these cells disseminate from primary tumors, as well as how they become established in distant tissues after they metastasize.

New faculty welcomed to Department of Biology

Assistant professors Joey Davis and Rebecca Lamason will spearhead research initiatives into fundamental cellular processes.

Raleigh McElvery | Department of Biology
September 11, 2017

MIT’s Department of Biology is welcoming two new assistant professors, Joey Davis and Rebecca Lamason, this September. The duo will augment the department’s efforts in basic research, probing fundamental facets of cellular processes like molecular degradation and bacterial infection.

“I am thrilled that Becky and Joey have joined our department,” says Alan Grossman, department head. “They bring new research areas and approaches that fit well with our overarching goals to help solve fundamental biological problems. I anticipate that their expertise and interests will enable collaborations within MIT and beyond.”

The arrival of Davis and Lamason brings the number of recent biology faculty additions to five since January.

Joey Davis

Joey Davis investigates how cells maintain a delicate internal balance of assembling and dismantling their own machinery, particularly macromolecules. A cell’s ability to keep the precarious balance of this process in check often diminishes with age, and when it goes awry, disease can ensue.

Born in Durango, Colorado, but raised in Long Beach, California, Davis became interested in how things were built by emulating his construction worker father. Assembling bicycles and other objects spurred Davis’ curiosity about the nuts and bolts of the natural world and he soon realized that, unlike bikes, biological systems were not so easily parsed.

Davis went on to earn dual bachelor’s degrees in biological engineering and computer science from the University of California at Berkeley. He arrived at MIT as a graduate student shortly thereafter, jointly advised by professors Robert Sauer and Tania Baker, both of whom are based in Building 68, where Davis will now run his own lab. He also served as a teaching assistant for 7.51 (Principles of Biochemical Analysis), and as an advisor to MIT’s team for the International Genetically Engineered Machines (iGEM) competition.

Davis became enthralled by molecular disassembly, particularly in bacteria. After a brief foray into the biotechnology sector, he returned to his California roots to pursue his postdoctoral training at the Scripps Research Institute in La Jolla. He brought with him his MIT-inspired fervor for large cellular machinery, and in doing so encountered his macromolecule of choice: the ribosome. Sometimes referred to by researchers as the “construction workers” of cells, ribosomes play a key role in building molecules from genetic blueprints. After three years, he was awarded a K99/R00 Pathway to Independence Award from the National Institute of Aging, which included an affiliation at the Sanford Burnham Prebys Medical Discovery Institute. The award will also help fund his first several years of research at MIT.

In his own lab, Davis seeks to determine how cells assemble and destroy ribosomes and other macromolecules, as well as how they remove harmful protein aggregates and dysfunctional organelles. These functions are often compromised due to age, genetic mutations, and environmental stresses, leading to diseases like cancer, diabetes, and neurodegenerative disorders. Davis says he is excited to further examine these processes at MIT.

“The questions I’m asking about how the degradation system is constructed and how it targets substrates are similar to those I pursued in graduate school — but the answers will likely be completely different,” Davis says. “The members of the MIT research community truly want to know how the natural world works, and that mindset draws me in today as much as it did 13 years ago.”

Davis has been hard at work developing a series of new research techniques, some involving cryo-electron microscopy, a method to image large macromolecules at high resolution. His discoveries could ultimately assist pharmaceutical development — improving antibiotics and anti-cancer therapeutics — and perhaps enabling scientists to one day engineer their own bigger and better molecules.

Rebecca Lamason

Rebecca Lamason investigates what happens when cellular functions are hijacked by unwanted interlopers — namely, the bacteria that cause diseases such as spotted fever and meningitis. Her interdisciplinary work spans multiple fields, including immunology, genetics, biochemistry, cell biology, and microbiology.

Growing up in a family that was interdisciplinary in its own right, composed of both artists and mechanics, Lamason has always sought to examine fundamental questions from multiple perspectives.

After earning a bachelor’s degree in molecular biology from Millersville University in Pennsylvania, she went on to graduate school at the Johns Hopkins University School of Medicine, where she immersed herself in the field of immunology. There she demonstrated how a molecule called CARD11 regulates immune cell activation, a discovery with potential applications for cancer therapeutics. She also served as a teaching assistant for the school’s graduate immunology course and co-founded the Immunology Student Journal Club.

It wasn’t until her postdoctoral training at the University of California at Berkeley, however, that Lamason found her model systems: two species of bacteria called Rickettsia parkeri and Listeria monocytogenes.

The two pathogens lay siege to cells in much the same way, entering and leveraging preexisting internal structures to build tails for rapid migration to neighboring cells. Lamason hypothesized that to do so, the intruders must also take over the complex communication systems between cells. Common scientific consensus held for years that Rickettsia, Listeria, and several other species of bacteria spread in a similar manner — using their tails to propel themselves and ram into the host’s cell wall to gain access to neighboring cells. Lamason, however, demonstrated this isn’t always the case and that Rickettsia tend to lose their tails and must then rely on the host cell’s internal machinery instead to invade neighboring cells.

Lamason was drawn to MIT by the diverse array of research efforts that are unified by a collaborative desire to explore the mechanistic details of cellular systems. Like Davis, she received a K99/R00 Pathway to Independence Award in 2015 — in her case from the National Institute of General Medical Sciences. Her lab will continue to investigate the interplay between invasive bacteria and their hosts, aiming to clarify how cell-to-cell spread varies between species. She plans to leverage advanced imaging platforms with tools from cell biology, microbiology, genetics, and biophysics to gain a deeper understanding of how these pathogens manipulate their hosts.

“My goal is to understand this virulence mechanism in order to prevent disease, and to use pathogens as tools to better understand host cell biology,” Lamason says. “This type of study lends itself naturally to interdisciplinary work. I love the challenge of learning new things and using multiple approaches to clarify important biological questions.”

Gene Brown, professor emeritus of biology, dies at 91

A pioneer in the field of intermediary metabolism and former dean of the School of Science, Brown’s deepest passion was teaching.

Vivian Siegel | Department of Biology
August 18, 2017

Gene M. Brown, MIT professor emeritus of biology, former department head, and former dean of the School of Science, passed away on Aug. 4 at the age of 91.

“He was really the heart and soul of the department for a very long time, devoted to undergraduates and to teaching,” says MIT Professor Lisa Steiner. Steiner, an expert in the evolution and development of the immune system, was hosted by Brown during her recruitment visit to MIT and became the first female faculty member hired in the Department of Biology. “The idea of the department without him is quite shocking.”

A pioneer in the field of intermediary metabolism, Brown’s research career focused on how living systems carry out chemical reactions in order to survive. He trained himself in enzymology after arriving at MIT, and he and his students and postdocs focused primarily on the enzymatic synthesis of several B vitamins, including thiamine, folic acid, riboflavin, and coenzyme A. He is best known for his work on the biosynthesis of folic acid and related compounds both in microorganisms and in the fruit fly Drosophila melanogaster, publishing over 100 research papers in his career.

“Gene was a wonderful research advisor and teacher,” says Linda Spremulli, professor emerita of chemistry at the University of North Carolina at Chapel Hill, who was a graduate student with Brown from 1969 to 1973. “He transformed my life, instilling in me a love for the beauty of metabolic pathways with their complex mechanisms.”

Growing up in rural Missouri and Idaho, Brown was the first member of his family to finish high school, and the only person in his graduating class to attend college. After a year as a college student in Idaho, Brown enlisted in the Army Air Forces, where he taught defensive measures against chemical warfare. After his term in the Army Air Forces, he returned to college at Colorado A & M College, where he majored in chemistry, graduating in 1949. He completed his graduate work at the University of Wisconsin in 1953 under the direction of Esmond Snell, isolating and characterizing the enzymatic synthesis of pantetheine, an analog of vitamin B5, and an intermediary in the production of coenzyme A.

Brown continued working with Snell as a postdoc at the University of Texas until he was recruited by Professor Jack Buchanan to join the newly forming biochemistry division of the MIT Department of Biology in 1954. Brown served as executive officer of the department from 1967 to 1972; as associate department head under Professor Boris Magasanik from 1972 to 1977; as department head from 1977 to 1985; and as dean of the School of Science from 1985 to 1991. While serving as dean of science, Brown closed his research program. He officially retired from MIT in 1996, but continued teaching until 2014.

Brown’s deepest passion was teaching. “As dean, he would leave meetings with the president of MIT to go teach,” recalls Professor Tom RajBhandary, who co-taught 7.05 (Introductory Biochemistry) with Brown for over 20 years. He was legendary for teaching intermediary metabolism without any notes, filling the boards of Room 10-250 with detailed pathways in meticulous handwriting. Brown got his first taste of teaching in high school, when his math and chemistry teachers would routinely call him to the board to explain the material. He was the first person in the Department of Biology to give open book and open note examinations, promoting the view that students should not have to memorize, but rather should be assessed for their ability to think and to solve problems. He was involved in teaching 7.05 for 60 years.

“I loved teaching with Gene and will miss him,” says Professor Matthew vander Heiden, who currently teaches 7.05. “The privilege to see how he taught the class has had a tremendous impact on my own approach to teaching. I think he would be pleased to know that the unique insights he provided continue to be passed on each spring, and will continue to be passed on as long as I am involved in the course.”

Teaching undergraduates was a value that extended throughout his career. As dean of science, he made it clear that the quality of teaching would be an important consideration for tenure decisions. He also co-chaired the committee that instituted the undergraduate communications requirement aimed at improving skills in both written and oral communications. The Department of Biology gives two teaching awards in his honor: The Gene Brown Prize, funded by Brown himself, recognizes teaching excellence among undergraduates; and the Gene Brown-Merck Teaching Award, funded by Merck and by Brown’s former graduate students and postdocs, recognizes teaching excellence among graduate students.

During Brown’s administrative tenure in biology, the MIT Center for Cancer Research (the predecessor of the Koch Institute for Integrative Cancer Research) and the Whitehead Institute were established with Department of Biology faculty leadership (Professor Salvador Luria for the Center for Cancer Research in 1974, and Professor David Baltimore for the Whitehead Institute in 1982).

A longtime resident of Concord, Massachusetts, Brown is survived by his children, James, Lindsey, and Holly, and his four grandchildren. He was predeceased by his wife, Shirley, and a brother, James.

Gifts in Brown’s name may be made to the Gene Brown Undergraduate Education Fund, fund No. 3839399. Donations in his memory will support undergraduates and undergraduate education in the MIT Department of Biology. For more information, contact Rebecca Chamberlain at 617-253-4729 or rchambe@mit.edu.

Department of Biology welcomes three new faculty members

Recent additions bring diverse expertise and cultural perspectives to research community.

Raleigh McElvery | Department of Biology
July 25, 2017

On July 1, MIT Department of Biology welcomed three new faculty members. Since they were all born outside the continental U.S., these newcomers add to the diversity of cultural experiences and contribute to the global face of science at MIT and its affiliated institutions around Kendall Square. The triad also enhances the department’s diverse array of research initiatives. Their interests are as far-reaching as their roots, and range from investigating genetic diseases and cancer immunotherapy to exploiting parasite vulnerabilities.

“When creative individuals with distinct perspectives and approaches come together in an innovative environment like MIT, the possibilities for scientific collaboration and accomplishment are exceptional,” says Alan Grossman, head of the department. “I couldn’t be more pleased to welcome three such outstanding and accomplished individuals into our research community.”

Eliezer Calo

Eliezer Calo is no stranger to MIT. Although he grew up on a farm more than a thousand miles away in the mountains of Carolina, Puerto Rico, Calo first set foot in MIT’s Building 68 11 years ago — and hasn’t wavered in his decision to become a biologist since. In 2006, as part of the MIT Summer Research Program (MSRP), Calo spent 10 weeks studying under Professor Stephen Bell, examining DNA replication. At the time, Calo was a chemistry major at the University of Puerto Rico, but returned post-graduation to MIT’s Department of Biology, earning his PhD while serving as both a teaching assistant for MIT’s course 7.01 (Introduction to Biology) and MSRP program assistant.

“MIT is very unique,” he says. “I’ve done research at multiple institutions, and yet nothing quite compares. Here, the impossible is made possible.”

After completing his postdoctoral training at Stanford University, Calo returned to Cambridge, Massachusetts, this past January as an assistant professor and extramural member at the Koch Institute to head his own lab — exploring the ways in which errors in cellular organelles called ribosomes can lead to disease.

Ribosomes are vital to the translation of genetic code into the molecules integral to life, but are far less often acknowledged for their role in embryonic development. Calo suggests that when ribosomes are not constructed correctly, they are unable to carry out their cellular duties, hindering cell growth and causing developmental disorders. Calo is interested in one condition specifically: Treacher Collins syndrome, which stems from a mutation in a single gene that impedes proper ribosomal assembly. He will soon transfer his experiments from cell cultures to a new model system — zebrafish — in order to further unravel the relationship between ribosome structure and disease.

“The research I do now is purely based on my interest in understanding how cells work,” Calo says. “Specifically, how the mechanisms controlling growth and proliferation operate. These are essential processes that led to the emergence of multicellular organisms, and thus to our own existence.”

Stefani Spranger

One building over in MIT’s Koch Institute, newly-appointed Assistant Professor Stefani Spranger will work to harness the body’s own defense force to pinpoint and eradicate cancer. Spranger carried her passion for immunotherapy across seas from Munich, Germany. As the daughter of two engineers, Spranger was raised on science. “My parents fostered my curiosity,” she says, “which led to my initial motivation to go into science: to figure out how things work.”

While earning her bachelor’s and master’s degrees from the Ludwig-Maximilians University of Munich, Spranger discussed publications focusing on two clinical trials that used engineered immune cells to combat malignant melanoma. These publications ignited Spranger’s enthusiasm for immune-based therapies, which in turn spurred her doctoral and postdoctoral training at the Helmholtz-Zentrum Munich in the Institute for Molecular Immunology and the University of Chicago, respectively.

While Spranger’s education helped hone her immunology research skills, she is excited to experience a more varied academic environment encompassing a range of disciplines. “I was drawn to MIT because of its diverse faculty and the breadth of research interests,” she says.

Spranger’s lab will employ tumor models in mice to determine how cancer and immune cells interact. In particular, she aims to discern the many factors related to the cells, tissues, and environment that could affect the immune system’s anti-tumor response. Ultimately, Spranger hopes to contribute to new treatments that trigger the body’s defense to thwart cancer.

Sebastian Lourido

Trained as both an artist and a scientist, Sebastian Lourido works to counter an entirely different kind of invader spreading biological mayhem: parasites. Originally from Colombia, he was recently named assistant professor of biology, joining the cohort of 15 faculty members at the Whitehead Institute for Biomedical Research — one of just 28 individuals to ever receive this appointment. The title may be new, but this is familiar turf for Lourido. He became a Whitehead Fellow in 2012, after receiving his PhD in microbiology from Washington University in St. Louis and a bachelor’s in studio art and cell and molecular biology from Tulane University. A pioneer in more ways than one, Lourido formed his own lab as a fellow rather than following a more conventional postdoc path.

Lourido spent much of his childhood exploring his mother’s genetics lab, where he analyzed practically anything he could fit under a microscope. “That experience solidified my excitement for the invisible mechanisms that make up the living world,” he says. “I can’t remember a time when I didn’t know that genetic information was carried in our cells in the form of DNA, and passed from one generation to the next.”

Constantly seeking ways to merge his artistic endeavors with scientific ones, Lourido leverages his creativity to glean insight into the systems and structures that constitute life.  He probes a group of microscopic invaders known as Apicomplexan parasites, revealing their weaknesses in order to devise potential treatments. Lourido’s team was the first to perform a genome-wide functional analysis of an apicomplexan — gaining deeper understanding of the genes and molecules key for the invasion process. In 2013, Lourido received the National Institutes of Health (NIH) Director’s Early Independence Award, and with it a five-year grant to investigate motility in one kind of parasite, Toxoplasma gondii. This same interloper is also the subject of Lourido’s two-year NIH-funded project, for which he is the principal investigator.

Lourido has found the MIT community both welcoming and inclusive. Even as he was interviewing for his new position, he was struck by the collaborative, collegial, and nurturing environment.

“This level of engagement permeates the other elements of our community — students, postdocs, and staff scientists — who drive the exciting research happening every day at MIT,” he says. “There are many forces that shape the diversity of our campus, and we need to be vigilant and work hard to continue to encourage and support scientists from different backgrounds, experiences, and cultures.”

A rose by any other name would smell as yeast

Emily Havens Greenhagen ’05 leads a team of scientists brewing perfume from yeast.

Justin Chen | Department of Biology
July 14, 2017

From afar, the multistory fermenters — towering metal cylinders encompassed by scaffolding, ladders, and pipes — look like rockets on a launch pad. Climbing to the top of the fermenter, visitors to the Mexico City manufacturing plant can peer down at a set of paddles churning 50,000 liters of frothy, golden broth. Within the mixture, genetically engineered yeast are synthesizing lactones — a family of molecules responsible for the aromas of fruits and flowers. MIT Department of Biology alumna Emily Havens Greenhagen ’05 has visited the plant over several weeks to monitor her company’s most promising project: a plan to make perfume from yeast cells.

Greenhagen is director of fermentation engineering at Ginkgo Bioworks, a Boston-based synthetic biology company seeking to turn microbes into customizable factories to produce products ranging from pesticides to perfumes. Scientists such as Greenhagen know that microbes can manufacture organic products more efficiently than any machine or production line. Instead of workers at an assembly line, yeast cells use enzymes — proteins that perform a specific task such as removing or adding a group of atoms to a molecule. Working together, teams of enzymes incrementally transform basic nutrients like sugar into other compounds such as alcohol and carbon dioxide. “By inserting DNA encoding for enzymes from different plants or animals into yeast cells,” Greenhagen says, “we can tailor microbes to produce different materials.”

Manipulating yeast cells is an old idea. For hundreds of years, people have been brewing beer through fermentation, a natural process where yeast consume sugar to create alcohol and different flavorings. In the 1930s, scientists began using microbes to create antibiotics and biofuels. “What makes Ginkgo cutting edge is the automation and scale,” Greenhagen explains of the company co-founded in 2008 by synthetic biologist Tom Knight ’69, SM ’79, PhD ’83. “Using robots, we can genetically modify hundreds of yeast strains and test how they perform in just one week.”

Ginkgo Bioworks’ automation played a critical role in creating the yeast strain that Greenhagen observed in the Mexico City manufacturing plant. These microbes, containing a set of enzymes needed to turn fatty acids into lactones, were engineered through thousands of trial-and-error experiments performed by robots. For each enzyme encoded in the final strain, a team of scientists and machines led by Greenhagen had tested hundreds of versions originating from diverse plant species and strategically mutated in different ways to work more efficiently in yeast cells.

During the testing process, researchers grew thousands of yeast strains, each genetically engineered for a single enzyme, in small tabletop fermenters before combining the most effective genetic modifications into a single cell to produce lactones. Ten years ago, when Greenhagen first started in industry, fermenting was a labor-intensive process done by hand, requiring a single researcher to manage four reactors at a time. In contrast, members of Greenhagen’s team — using robots to mix different concentrations of nutrients, add yeast extract, and monitor the output of desired molecules — routinely managed 24 experiments simultaneously. As a result of automation, the development process took six months instead of a year and half. After a purification process, the developed scent could then be delivered to Robertet, a French fragrance and flavor manufacturer and Ginkgo’s first commercial customer. “The robots don’t just speed up projects,” Greenhagen says, “they take care of the monotonous tasks so that we have more time to think about results and design new experiments — the fun stuff that scientists really want to do.”

Like Ginkgo Bioworks, Greenhagen embodies the convergence of biology and engineering. As a freshman at MIT, Greenhagen had decided to pursue chemical engineering but changed her plans when she learned about synthetic biology. “I couldn’t stop reading my textbook,” she recalls. “I was so excited by the idea that there are living organisms that we can modify to use as tools. That’s when I decided to become a scientist.”

Greenhagen credits one particular microbiology course, taught by Professor Graham Walker, for shaping her thinking as a biologist. While lecturing on organelles, Walker encouraged students to imagine the room as a cell and to point out where the nucleus or mitochondria might be located. “His teaching style inspired me to really visualize what’s going on in the fermentation vessel,” Greenhagen says. “Whereas fermentation engineers worry more about physical variables like oxygen transfer and think of organisms as black boxes, my training at MIT gave me an empathy for microbes. It’s an approach that a lot of chemical engineers don’t necessarily think about and has been key to my success.”

By harnessing biology and engineering, Greenhagen and others in the field of synthetic biology are beginning to transform manufacturing. Many consumer goods, from food to clothes to perfume, are produced using traditional ingredients and industrial processes that are increasingly unsustainable as planetary resources dwindle. By using microbes, companies can generate many of the raw resources they require with less energy and waste than factories.

In the case of flavors and fragrances, companies like Robertet had been extracting the majority of their starting compounds from plants and flowers, whose growth may vary dramatically from year to year. In contrast, Ginkgo Bioworks’s yeast feed on basic crops like corn and sugar cane, which are more economical to raise, and release their products in highly reliable reactions. Encouraged by its success with perfumes, Ginkgo Bioworks is using similar approaches to make organic pesticides, industrial enzymes, and products for human health.

For Greenhagen, scented yeast represent not only the potential of synthetic biology but also the culmination of years of work and education. Before joining Ginkgo Bioworks, Greenhagen had spent six years at another startup without seeing any of her projects commercialized. “When we were bought out by a larger company and taken off the commercialization path, I was told to sit back and relax but that’s not what I do,” she says.

Greenhagen traces her driving mentality back to MIT lab courses and an Undergraduate Research Opportunities Program (UROP) project in Professor Leona Samson’s laboratory. There, Greenhagen says, students were expected to read papers, design their own experiments, and place their findings in the context of published results. “This critical thinking and problem solving combined with real-life experience inspired me to think of my education as a gift that I should put to use,” she says. Years later, having traveled thousands of miles to see her first commercialized product, Greenhagen says she is still moved by MIT. “When I walk through campus, I get goosebumps from all the memories. It is such an amazing place.”

School of Science professors granted tenure

Seven award-winning faculty members represent the departments of Physics, Chemistry, and Biology.

Bendta Schroeder | School of Science
June 28, 2017

The School of Science has announced that seven of its faculty members have been granted tenure by MIT.

This year’s newly-tenured professors are:

Mircea Dincă, associate professor in the Department of Chemistry, addresses research challenges related to the storage and consumption of energy and global environmental concerns through the synthesis and characterization of new inorganic and organic materials. His work has applications in heterogeneous catalysis, energy conversion and storage, chemical sensing, gas separation, and water-based technologies including adsorption heat pumps and water production and purification. By designing and synthesizing new materials, Dincă aims to learn more about fundamental processes such as electron and ion transport through ordered solids, the reactivity and electrochemistry of low-coordinate metal ions in porous crystals, the effects of conformational changes on the electronic properties of molecules, and the behavior of materials at the interface with solid-state devices.

Dincă earned a BS in chemistry at Princeton University and a PhD in inorganic chemistry at the University of California at Berkeley. Following a postdoc appointment at MIT in the Department of Chemistry, he joined its faculty in 2010. Among Dincă’s awards and honors are an Alfred P. Sloan Research Fellowship, a Camille Dreyfus Teacher-Scholar Award, and the Alan T. Waterman Award

Liang Fu, the Lawrence C. (1944) and Sarah W. Biedenharn Career Development Assistant Professor in the Department of Physics, is interested in novel topological phases of matter and their experimental realizations. He works on the theory of topological insulators and topological superconductors, with a focus on predicting and proposing their material realizations and experimental signatures. He is also interested in potential applications of topological materials, ranging from tunable electronics and spintronics, to quantum computation.

Fu obtained a BS in physics from the University of Science and Technology of China and a PhD in physics from the University of Pennsylvania. Following an appointment as a Junior Fellow at Harvard University, he joined the MIT faculty in 2012. Fu is the recipient of a Packard Fellowship for Science and Engineering and the New Horizons in Physics Prize.

Jeff Gore, associate professor in the Department of Physics, uses experimentally-tractable microcosms such as bacterial communities to explore the physics of complex living systems, examining how interactions between individuals drives the evolution and ecology of communities. Gore’s primary areas of research include the behavior of populations near tipping points that lead to collapse, the evolution of cooperative behaviors within a species or community, and the determining factors for multi-species diversity within a community.

Gore received a BS in physics, mathematics, economics, and electrical engineering from MIT and a PhD in physics from the University of California at Berkeley. He returned to MIT as a Pappalardo Postdoctoral Fellow in the Department of Physics and subsequently joined the faculty in 2010. Gore’s awards and honors include an Allen Distinguished Investigator Award, an NIH Director’s New Innovator Award, and a National Science Foundtion CAREER Award.

Jeremiah Johnson, the Firmenich Career Development Associate Professor in the Department of Chemistry, designs macromolecules and their syntheses to address problems in chemistry, medicine, biology, energy, and polymer physics. Johnson works with a range of materials and applications, including nano-scale, brush-arm star polymer architectures for in vivo drug delivery, imaging, and self-assembly; hydrogels for the analysis of how molecular network defects impact mechanics; and polymers for surface functionalization and energy storage.

Johnson completed a BS in biomedical engineering and chemistry at Washington University in St. Louis and a PhD in chemistry at Columbia University. Following an appointment as a Beckman Institute Postdoctoral Scholar at the Caltech, Johnson joined the MIT faculty in 2011. Johnson is the recipient of several awards including an Alfred P. Sloan Research Fellowship and a 3M Non-Tenured Faculty Award.

Brad Pentelute, the Pfizer-Laubach Career Development Associate Professor in the Department of Chemistry, modifies naturally occurring proteins to enhance their therapeutic properties for human medicine, focusing on the use of cysteine arylation to generate abiotic macromolecular proteins, the precision delivery of biomolecules into cells, and the development of fast flow platforms to rapidly produce polypeptides.

Pentelute earned a BS in chemistry and a BA in psychology at the University of Southern California, followed by a PhD in organic chemistry at the University of Chicago. After a postdoc fellowship at Harvard Medical School, Pentelute joined the MIT faculty in 2011. His awards and honors include an Alfred P. Sloan Research Fellowship, a Novartis Early Career Award, and an Amgen Young Investigator Award.

Jesse Thaler, associate professor of physics and member of the Laboratory for Nuclear Science, is a theoretical particle physicist whose research focus is the Large Hadron Collider (LHC) experiment at CERN. Thaler aims to maximize the discovery potential of the LHC by applying theoretical insights from quantum field theory. He is particularly interested in novel methods to test the properties of dark matter at the LHC and beyond, as well as the theoretical structures and experimental signatures of supersymmetry. Thaler also develops new methods to characterize jets, which are collimated sprays of particles that are copiously produced at the LHC. These techniques exploit the substructure of jets to enhance the search for new physics as well as to illuminate the structure of the standard model itself.

Thaler received his PhD in physics from Harvard University and his BS in mathematics and physics from Brown University. After a fellowship at the Miller Institute for Basic Research in Science at the University of California at Berkeley, he joined the MIT faculty in the Department of Physics in 2010. His awards and honors include an Early Career Research Award from the U.S. Department of Energy, a Presidential Early Career Award for Scientists and Engineers from the White House, an Alfred P. Sloan Research Fellowship, and an MIT Harold E. Edgerton Faculty Achievement Award.

Matthew Vander Heiden is the Eisen and Chang Career Development Associate Professor in the Department of Biology. His laboratory is studying how mammalian cell metabolism is adapted to support function, with a particular focus on the role metabolism plays in cancer. He uses mouse models to study how changes in metabolism impact all aspects of cancer progression with a goal of finding novel ways to exploit altered metabolism to help patients.

Vander Heiden earned a BS, an MD, and a PhD from the University of Chicago, and completed his clinical training in internal medicine and medical oncology at the Brigham and Women’s Hospital and the Dana-Farber Cancer Institute. After postdoctoral research at Harvard Medical School, Vander Heiden joined the faculty of the MIT Department of Biology and the Koch Institute in 2010. Among Vander Heiden’s awards and honors include a Burroughs Wellcome Fund Career Award for Medical Sciences, a Damon Runyon-Rachleff Innovation Award, a Stand Up To Cancer Innovative Research Grant, and being named a Howard Hughes Medical Institute Faculty Scholar.

STEX event showcases innovations in fitness technology and science

Entrepreneurs, researchers, and industry experts build connections at workshop.

Rob Matheson | MIT News Office
June 26, 2017

Many MIT-affiliated startups are innovating in the burgeoning fitness technology and science space, aiming to promote healthier lifestyles and help optimize athletic performance.

Novel products from these startups include a smart chair that fights back pain and diabetes, a sleeve that monitors muscle-movement data that users can share in the cloud, a wristband that tracks blood oxygen levels for greater performance, and even a so-called anti-aging pill.

A workshop hosted June 22 by the MIT Office Corporate Relations’ (OCR) MIT Startup Exchange (STEX) program brought together some of these MIT entrepreneurs and industry experts to showcase their innovations and foster connections that could lead to new business opportunities.

Held throughout the year, the three-hour STEX workshops include lightning presentations from MIT-connected startups; brief talks from academic innovators, industry experts, government representatives, and venture capitalists; startup presentation and demonstration sessions; and an interactive panel discussion.

At last week’s event, eight entrepreneurs pitched their fitness-tech products — several rooted in MIT research — to a crowd of around 80 entrepreneurs, researchers, and industry experts in the OCR headquarters on Main Street, in Cambridge, Massachusetts. The academic keynote speaker was MIT Novartis Professor of Biology Leonard Guarente, who took the opportunity to demystify the science behind his startup Elysium Health’s “anti-aging pill,” which is made of compounds that aim to thwart age-related cell damage, which can lead to inflammatory and heart diseases, osteoporosis, and diabetes.

STEX events aim to stimulate discussion, foster collaboration, and build partnerships between MIT-connected startups and member companies of MIT’s Industrial Liaison Program (ILP). The series covers a broad range of topics: a recent workshop focused on energy storage, while upcoming events will focus on synthetic biology, robotics and drones, cancer therapies, renewable energy, world water issues, and 3-D printing.

“Fitness, wellness and nutrition are very exciting areas, and MIT founders are very active in the space. We certainly have industry coming to campus interested in all of these technologies and products coming from them,” Trond Undheim, who directs STEX and is the organizer of the event, said in his opening remarks.

Presenter Simon Hong, a researcher in the McGovern Institute for Brain Research at MIT, and CEO of smart-chair startup Robilis, said last week’s STEX workshop provided “an opportunity to interact with potential stakeholders.”

Based on neuroscience research, Robilis developed StandX, a chair with two automated moving halves, side by side. The halves alternate — one dropping down and the other staying straight — making the user sit down on one half while standing on the opposite leg. The frequent alternation prevents stress on the spine caused by sitting in one position for extended periods, and the chair’s design encourages proper posture. The movement also interrupts prolonged sitting, which is associated with diabetes.

During a startup demonstration session midway through the event, Hong’s station was crowded with attendees looking to try out the chair. In the end, he walked away with a few contacts interested in helping with production and in introducing him to potential investors. “I was quite satisfied with the event,” Hong told MIT News. “It is in a way a networking event, and good things tend to happen quite unexpectedly during many, many interactions with people.”

Apart from providing a venue to spread the word about his wearables, the event enabled Alessandro Babini MBA ’15, co-founder of Humon, to connect with larger organizations in the space. Humon, a wearable targeted at endurance athletes, attaches to a muscle, where it monitors blood oxygen levels by shining a light into the skin and analyzing changes in the light that indicate less or more oxygen.

“It was interesting to get an understanding about what big brands seek in partners, what they’re looking to invest in, and what they’re working on now,” Babini told MIT News. “Big corporations have a lot of customers and a big influence on where the market is going.”

Another interesting MIT spinout, figure8, presented a wearable that captures 3-D body movement that can be analyzed by the user or shared with an online community — like a “YouTube” of movement data.

The wearable is a small sleeve made from novel sensor-woven fabric that fits over the arm or leg to track joint and muscle movement. It lets users map the movement of muscle, bone, and ligaments. Put on a knee, for instance, the wearable can map individual ligaments, which is valuable for, say, monitoring the anterior cruciate ligament (ACL). One application is in physical therapy, so athletes can track injuries as they heal.

Users can also map their movement to others. Dancers, for instance, can use the sensor to match their movements to those of others during training. The startup is also developing a platform that lets users upload and share that data in the cloud.

“Before YouTube, no one thought about video as something you can share, upload, and download as a commodity,” said co-founder and CEO Nan-Wei Gong, an MIT Media Lab researcher, during her presentation. “We’re trying to create a system for everyone to collect this motion [data] they can upload and download.”

Other startups that presented included: Kitchology, Fitnescity, Digital Nutrition, Food for Sleep, and SplitSage.

In his keynote, Guarente explained the science and history behind Elysium’s “anti-aging” pill, called Basis, which he himself has been taking for three years. He noted the pill doesn’t necessarily make people feel more youthful or healthier, especially if they’re already healthy. “You should just fall apart more slowly,” Guarente said to laughter from the audience.

Years ago, Guarente and other MIT researchers identified a group of genes called sirtuins that have been demonstrated to slow the aging process in microbes, fruit flies, and mice. For instance, calorie-restricted diets, long known to extend lifespans and prevent many diseases in mammals, is key in activating sirtuins. “It turns out there are compounds that can do the same thing,” Guarente said.

It was later discovered that one of those compounds is abundant in blueberries and that an enzyme called nicotinamide adenine dinucleotide (NAD) is essential in carrying out the activity of sirtuins. But NAD deteriorates with age. “If there’s not enough NAD, you don’t activate sirtuins. Metabolism and DNA-repair goes awry, and a lot of things go wrong,” he said.

However, in the NAD synthesis pathway, NAD’s precursor, called nicotinamide riboside (NR), can be injected into an organism, where it would move efficiently into cells and be converted into NAD.

Basis is a combination of NR and the sirtuin-activating compound from blueberries.

Last year, Elysium conducted a 120-person trial. The results indicated that the pills were safe and led to an increase and sustainability of NAD levels. More trials are on the way, and the startup is growing its pipeline of products. It has not yet been shown whether Basis can extend life-span in humans.

“We could really make a difference in people’s health,” Guarente said at the conclusion of his talk. “And it would add to all the … medical devices and DNA analysis and motion sensors, so that people can begin to do what they want to do, which is to take charge of their health.”

The investor speaker was David T. Thibodeau, managing director of Wellvest Capital, an investment banking company specializing in healthy living and wellness. The industry speaker was Matthew Decker, global technical leader in the Comfort and Biophysics Group of W.L. Gore and Associates, the manufacturing company best known for Gore-Tex fabrics.

Panelists were Guarente, Decker, Thibodeau, and Josh Sarmir, co-founder and CEO of SplitSage, an MIT spinout that is developing an analytics platform that can detect “sweet spots” and “blind spots” in people’s fields of vision to aid in sports performance, online advertising, and work safety, among other applications.

STEX has a growing database of roughly 1,200 MIT-affiliated startups. Last year, OCR, in close partnership with ILP, created STEX25, an accelerator for 25 startups at any time that focuses on high-level, high-quality introductions. The first cohort of 14 startups have gone through the accelerator, gaining industry partnerships that have led to several pilots, partnerships, and lead client relationships.

Microbe generates extraordinarily diverse array of peptides

In marine bacteria, evolution of new specialized molecules follows a previously unknown path.

David L. Chandler | MIT News Office
June 22, 2017

It’s one of the tiniest organisms on Earth, but also one of the most abundant. And now, the microscopic marine bacteria called Prochlorococcus can add one more superlative to its list of attributes: It evolves new kinds of metabolites called lanthipeptides, more abundantly and rapidly than any other known organism.

While most bacteria contain genes to pump out one or two versions of this peptide, Prochlorococcus varieties can each produce more than two dozen different peptides (molecules that are similar to proteins, but smaller). And though all of Earth’s Prochlorococcus varieties belong to just a single species, some of their localized varieties in different regions of the world’s oceans each produce a unique collection of thousands of these peptides, unlike those generated by terrestrial bacteria.

The startling findings, published this week in the journal Proceedings of the National Academy of Science, were discovered by former MIT graduate student Andres Cubillos-Ruiz, Institute Professor Sallie “Penny” Chisholm, University of Illinois chemistry professor Wilfred van der Donk, and two others.

“This is incredibly significant work,” says Eric Schmidt, professor of medicinal chemistry at the University of Utah, who was not involved in the research. “The authors show how nature has evolved methods to create chemical diversity. What really sets it apart is that it examines how this evolution takes place in nature, instead of in the lab. They examine a huge habitat, the open ocean. This is amazing,” he says.

“No one had seen the true extent of the diversity in these molecules” until this new study, Cubillos-Ruiz says. The first hints of this unexpected diversity surfaced in 2010, when Bo Li and Daniel Sher, members of van der Donk’s and Chisholm’s labs respectively, found that one variety of Prochlorococcus could produce as many as 29 different lanthipeptides. But the big surprise came when Cubillos-Ruiz looked at other populations and found that the same organisms, in a different location, produced similarly great numbers of the peptides, “and all of them were completely different,” he says.

After considerable study examining the genomes of many Prochlorococcus cultures and pieces of DNA from the wild, the researchers determined that the way the extraordinary numbers of lanthipeptides evolve is, in itself, something that hasn’t been observed before. While most evolution takes place through tiny incremental changes, while preserving the vast majority of the genetic structure, the genes that enable Prochlorococcus to produce these lanthipeptides do just the opposite. They somehow undergo dramatic, wholesale changes all at once, resulting in the production of thousands of new varieties of these metabolites.

Cubillos-Ruiz, who is now a postdoc at MIT’s Institute For Medical Engineering and Science, says the way these genes were changing “wasn’t following classic phylogenetic rules,” which dictate that changes should happen slowly and incrementally to avoid disruptive changes that impair function. But the story is a bit more complicated than that: The specific genes that encode for these lanthipeptides are composed of two parts, joined end to end. One part is actually very well-preserved across the lineages and different populations of the species. It’s the other end that goes through these major shakeups in structure. “The second half is amazingly variable,” he says. “The two halves of the gene have taken completely different evolutionary pathways, which is uncommon.”

The actual functions of most of these thousands of peptides, which are known as prochlorosins, remain unknown, as they are very difficult to study under laboratory conditions. Similar compounds produced by terrestrial bacteria can serve as chemical signaling devices between the organisms, while others are known to have antimicrobial functions, and many others serve purposes that have yet to be determined. Because of the known antimicrobial functions, though, the team thinks it will be useful to screen these compounds to see if they might be candidates for new antibiotics or other useful biologic products.

This evolutionary mechanism in Prochlorococcus represents “an intriguing mode of evolution for this kind of specialized metabolite,” Cubillos-Ruiz says. While evolution usually favors preservation of most of the genetic structure from the ancestor to the descendants, “in this organism, selection seems to favor cells that are able to produce many and very different lanthipeptides. So this built-in collective diversity appears to be part of its function, but we don’t yet know its purpose. We can speculate, but given their variability it’s hard to demonstrate.” Maybe it has to do with providing protection against attack by viruses, he says, or maybe it involves communicating with other bacteria.

“Prochlorococcus is trying to tell us something, but we don’t yet know what that is,” says Chisholm, who has joint appointments in MIT’s departments of Civil and Environmental Engineering and Biology. “What [Cubillos-Ruiz] uncovered through this molecule is an evolutionary mechanism for diversity.” And that diversity clearly must have very important survival value, she says: “It’s such a small organism, with such a small genome, devoting so much of its genetic potential toward producing these molecules must mean they are playing an important role. The big question is: What is that role?”

In fact, this kind of process may not be unique — it may be just that Prochlorococcus, an organism that Chisholm and her colleagues initially discovered in 1986 and have been studying ever since, has provided the wealth of data needed for such an analysis. “This might be happening in other kinds of bacteria,” Cubillos-Ruiz says, “so maybe if people start looking into other environments for that kind of diversity,” it may turn out not to be unique. “There are some hints it happens in other [biological] systems too,” he says.

Christopher Walsh, emeritus professor of biological chemistry and molecular pharmacology at Harvard University, who was not involved in this work, says “The dramatic diversity of prochlorosins assembled by a single enzyme … raises surprising questions about how evolution of thousands of cyclic peptide structures can be  accomplished by alterations that favor large changes rather than incremental ones.”

According to Schmidt, “There are many possible practical applications. The first is fairly clear: By using this natural variation, the same process can be used to design and build chemicals that might be drugs or other materials. More fundamentally, by understanding the natural process of generating chemical diversity, this will help to create methods to synthesize desired applications in cells.”

The research team also included former graduate student Jessie Berta-Thompson and postdoc Jamie Becker at MIT. The work was supported by the Gordon and Betty Moore Foundation, the National Science Foundation, and the Simons Foundation.

Pew recognizes four MIT researchers for innovation in biomedical science

Biophysicist Ibrahim Cissé and cell biologist Gene-Wei Li honored as Pew Scholars; postdocs Ana Fiszbein and María Inda are named Pew Latin American Fellows.

Julia C. Keller | School of Science
June 20, 2017

The Pew Charitable Trusts has named Ibrahim Cissé, assistant professor of physics, and Gene-Wei Li, assistant professor of biology, as 2017 Pew Scholars in the Biomedical Sciences. In addition, two postdocs, Ana Fiszbein and María E. Inda, were named to the 2017 class of Pew Latin American Fellows in the Biomedical Sciences in computational biology and synthetic biology, respectively.

The Pew Scholars program encourages early-career scientists to pursue innovative research to advance the understanding of human biology and disease. This year, 22 Pew Scholars will receive $240,000 over four years and gain inclusion into a select community of scientists that includes three Nobel Prize winners, five MacArthur Fellows, and five recipients of the Albert Lasker Medical Research Award. The applicants, who conduct research in all areas of biomedical sciences, must be nominated by one of 180 invited institutions. To date, the program has invested in more than 900 scholars.

“Pew’s biomedical programs not only provide young scientists with the flexibility to pursue creative ideas; they also spark interdisciplinary thinking and collaborations that can open new paths in the search for answers,” says Craig C. Mello, who won the 2006 Nobel Prize for physiology or medicine, was a 1995 Pew Scholar, and chairs the Pew Scholars National Advisory Committee.

Cissé, the MIT Class of 1922 Career Development Assistant Professor, says “support from Pew at an early stage is great encouragement in pushing my lab further at the frontiers of different fields.”

Cissé’s research group is investigating the fundamental processes involved in gene activation. Using a combination of techniques in cell and molecular biology, biochemistry, genomics, and super-resolution microscopy, he will continue his investigations of the behaviors of the enzyme involved in the transcription of DNA to RNA molecules. The enzyme, RNA polymerase II, has been well-studied in vitro, but Cissé’s work looks at these transient biological interactions within living cells. His findings will deepen the understanding of these processes, disruptions in which are linked to human disease, including most cancers.

Li’s research looks at evolution of cells’ production of proteins to answer a fundamental biological question of how cells specify how much of each type of protein to produce. In Li’s Quantitative Biology Lab, researchers have developed a technique for measuring the precise production rates of every protein in a cell. Combining this approach with other techniques in cell, molecular, and computational biology, Li is comparing a broad range of organisms across evolutionary distances to determine whether all of their proteins are maintained at some preferred level. By artificially perturbing the quantities of selected proteins, Li can explore the mechanisms cells use to reestablish the proper protein balance to better understand when misregulation occurs that leads to disease.

“The success of my research hinges on close integration between expertise in biological and physical sciences, as well as constant stimulation from both disciplines,” says Li, the Helen Sizer Career Development Assistant Professor. “The Pew scholarship will also provide a unique opportunity to interact with the brightest young minds in the biomedical sciences outside my field that will elevate my research to unanticipated levels.”

Each year, current scholars come together to discuss their research and learn from peers in fields outside of their own. “I am looking forward to interacting with other Pew scholars, many of whom are also working on paradigm-shifting ideas,” says Cissé.

Rebecca W. Rimel, president and CEO of The Pew Charitable Trusts calls the scholars an “impressive group” that has demonstrated “the curiosity and courage that drive great scientific advances, and we are excited to help them fulfill their potential.”

The Pew Latin American Fellows program, meanwhile, is intended to support postdocs from Latin America. Winners are awarded two years of funding to conduct research at laboratories and academic institutions in the United States.

The program also provides additional funding to awardees who return to Latin America to launch their own research labs after the completion of their fellowships. About 70 percent of program participants have taken advantage of this incentive and are conducting work on regional and global health challenges in nine Latin American countries, according to The Pew Charitable Trusts.

“Almost 150 young scientists have returned to their home countries and established independent research labs, providing critical groundwork for biomedical research across Latin America,” says Torsten N. Wiesel, the 1981 Nobel laureate in physiology or medicine and chair of the Latin American Fellows National Advisory Committee.

Ten Pew Latin American Fellows were named this year. The fellowship provides a $30,000 salary stipend to support two years of research, as well as an additional $35,000 for laboratory equipment should the fellow return to Latin America to start his or her own lab. Since the program’s inception in 1990, the program has supported almost 150 young Latin American scientists.

Ana Fiszbein is a postdoc working in the Burge Lab, where she researches the role that changes in gene splicing could play in the biology of normal and tumor cells, with the goal of revealing novel targets for cancer therapeutics. “I am very honored to receive this award, it is a privilege and also a responsibility,” she says. Fiszbein is working with Professor Christopher B. Burge, of the departments of Biology and Biological Engineering and the Broad Institute of MIT and Harvard.

“Ana is an exceptionally talented molecular biologist and independent thinker who came to my lab very well trained from her PhD in Alberto Kornblihtt’s lab,” Burge says. “She has developed very interesting hypotheses about the mechanistic connections between transcription and RNA splicing.”

The activity of genes can be regulated on many levels, including how often DNA is read to produce an RNA, where within the gene that reading begins, and which of the gene’s segments are represented in the RNA molecules that ultimately direct the formation of protein. Tumor cells harbor genetic changes that can alter all three of these points of control. However, little is known about the control of these regulatory processes or how they might be interconnected. Fiszbein is working on a sequence study of RNA in different species, with a sequence analysis of human cancer genomes to identify RNAs that may be present more often in cancer cells. She will then assess whether those RNA segments are co-regulated with the sites where the reading of a gene begins.

Inda is a postdoc working in the lab of Timothy Lu, an assistant professor leading the Synthetic Biology Group in the departments of Electrical Engineering and Computer Science and Biological Engineering. In the Lu Lab, she will work on the development of novel noninvasive strategies, for the early diagnosis and alleviation of inflammation in intestinal disorders, such as inflammatory bowel disease (IBD).

“The fellowship provides me a unique opportunity to learn the practical and theoretical underpinnings of cutting-edge research in the synthetic biology field for diagnosis and treatment of serious ailments,” she says.

A variety of bacteria inhabit healthy human intestines, and members of the Lu laboratory have been working to commandeer some of these microbes for use as sentinels that could patrol the gut and secrete therapeutic molecules in areas that appear inflamed. Inda plans to equip bacteria with biosensors that recognize the molecular markers of IBD — and then trigger the release of anti-inflammatory compounds. She will then assess the engineered microbes’ ability to distinguish between diseased and healthy tissue and to treat inflammation in an animal model of IBD.

Wiesel has high praise for the quality of this year’s Latin American Scholars. “The 2017 class is again made up of researchers of outstanding promise who will no doubt continue to enhance the growing biomedical research community in the region,” he says.

How cells combat chromosome imbalance

Biologists discover the immune system can eliminate cells with too many or too few chromosomes.

Anne Trafton | MIT News Office
June 19, 2017

Most living cells have a defined number of chromosomes: Human cells, for example, have 23 pairs. As cells divide, they can make errors that lead to a gain or loss of chromosomes, which is usually very harmful.

For the first time, MIT biologists have now identified a mechanism that the immune system uses to eliminate these genetically imbalanced cells from the body. Almost immediately after gaining or losing chromosomes, cells send out signals that recruit immune cells called natural killer cells, which destroy the abnormal cells.

The findings raise the possibility of harnessing this system to kill cancer cells, which nearly always have too many or too few chromosomes.

“If we can re-activate this immune recognition system, that would be a really good way of getting rid of cancer cells,” says Angelika Amon, the Kathleen and Curtis Marble Professor in Cancer Research in MIT’s Department of Biology, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the study.

Stefano Santaguida, a research scientist at the Koch Institute, is the lead author of the paper, which appears in the June 19 issue of Developmental Cell.

“A downward spiral”

Before a cell divides, its chromosomes replicate and then line up in the middle of the cell. As the cell divides into two daughter cells, half of the chromosomes are pulled into each cell. If these chromosomes fail to separate properly, the process leads to an imbalanced number of chromosomes in the daughter cells — a state known as aneuploidy.

When aneuploidy occurs in embryonic cells, it is almost always fatal to the organism. For human embryos, extra copies of any chromosome are lethal, with the exceptions of chromosome 21, which produces Down syndrome; chromosomes 13 and 18, which lead to developmental disorders known as Patau and Edwards syndromes; and the X and Y sex chromosomes, extra copies of which may cause various disorders but are not usually lethal.

In recent years, Amon’s lab has been exploring an apparent paradox of aneuploidy: When normal adult cells become aneuploid, it impairs their ability to survive and proliferate; however, cancer cells, which are nearly all aneuploid, can grow uncontrollably.

“Aneuploidy is highly detrimental in most cells. However, aneuploidy is highly associated with cancer, which is characterized by upregulated growth. So, a very important question is: If aneuploidy hampers cell proliferation, why are the vast majority of tumors aneuploid?” Santaguida says.

To try to answer that question, the researchers wanted to find out more about how aneuploidy affects cells. Over the past few years, Santaguida and Amon have been studying what happens to cells immediately after they experience a mis-segregation of chromosomes, leading to imbalanced daughter cells.

In the new study, they investigated the effects of this imbalance on the cell division cycle by interfering with the process of proper chromosome attachment to the spindle, the structure that holds chromosomes in place at the cell’s equator before division. This interference leads some chromosomes to lag behind and get shuffled into the two daughter cells.

The researchers found that after the cells underwent their first division, in which some of the chromosomes were unevenly distributed, they soon initiated another cell division, which produced even more chromosome imbalance, as well as significant DNA damage. Eventually, the cells stopped dividing altogether.

“These cells are in a downward spiral where they start out with a little bit of genomic mess, and it just gets worse and worse,” Amon says.

“This paper very convincingly and clearly shows that when chromosomes are lost or gained, initially cells can’t tell if their chromosomes have mis-segregated,” says David Pellman, a professor of pediatric oncology at Dana-Farber Cancer Institute who was not involved in the study. “Instead, the imbalance of chromosomes leads to cellular defects and an imbalance of proteins and genes that can significantly disrupt DNA replication and cause further damage to the chromosomes.”

Targeting aneuploidy

As genetic errors accumulate, aneuploid cells eventually become too unstable to keep dividing. In this senescent state, they start producing inflammation-inducing molecules such as cytokines. When the researchers exposed these cells to immune cells called natural killer cells, the natural killer cells destroyed most of the aneuploid cells.

“For the first time, we are witnessing a mechanism that might provide a clearance of cells with imbalanced chromosome numbers,” Santaguida says.

In future studies, the researchers hope to determine more precisely how aneuploid cells attract natural killer cells, and to find out whether other immune cells are involved in clearing aneuploid cells. They would also like to figure out how tumor cells are able to evade this immune clearance, and whether it may be possible to restart the process in patients with cancer, since about 90 percent of solid tumors and 75 percent of blood cancers are aneuploid.

“At some point, cancer cells, which are highly aneuploid, are able to evade this immune surveillance,” Amon says. “We have really no understanding of how that works. If we can figure this out, that probably has tremendous therapeutic implications, given the fact that virtually all cancers are aneuploid.”

The research was funded, in part, by the National Institutes of Health, the Kathy and Curt Marble Cancer Research Fund, the American Italian Cancer Foundation, a Fellowship in Cancer Research from Marie Curie Actions, the Italian Association for Cancer Research, and a Koch Institute Quinquennial Cancer Research Fellowship.