Author: mantulin

Department of Biology hosts second annual Science Slam

Eight biology contestants get one slide and three minutes to explain their research and impress their listeners.

Raleigh McElvery | Department of Biology
April 30, 2019

Trainees recently took over the Tuesday Biology Colloquium for the second annual Science Slam, hosted by MIT’s Department of Biology. Topics ranged from the science behind cancer metastasis to parasites, hangovers, and, notably, poop.

A science slam features a series of short presentations where researchers explain their work in a compelling manner, and — as the name suggests — make an impact. These presentations aren’t just talks, they’re performances geared towards a science-literate but non-specialized public audience. In this case, competitors were each given one slide and three minutes to tell their scientific tales and earn votes from audience members and judges.

The latter included Mary Carmichael, founder and CEO of the strategic communications consultancy Quark 4; John Pham, editor-in-chief of Cell; and Ari Daniel, an independent science reporter who crafts digital videos for PBS NOVA and co-produces the Boston branch of Story Collider.

Among the competitors were six graduate students and two postdocs who hailed from labs scattered throughout Building 68, the Whitehead Institute, and the Koch Institute for Integrative Cancer Research at MIT. In order of appearance:

  • Rebecca Silberman, from Angelika Amon’s lab, who spoke about how there is something special about cancer cells that allows them to thrive with the wrong number of chromosomes;
  • Tyler Smith, from Sebastian Lourido’s lab, who spoke about his organism of choice, Toxoplasma gondii, and how these parasites provide insights into fundamental biology that classic “model” organisms do not;
  • Jasmin Imran Alsous, from Adam Martin’s lab, who spoke about the coordinated cellular interactions required for fruit fly egg development;
  • Darren Parker, from Gene-Wei Li’s lab, who spoke about the ratio of ingredients needed to concoct nature’s winning recipe for the perfect cell;
  • Sophia Xu, from Jing-Ke Weng’s lab, who spoke about the molecules responsible for the kudzu flower’s capacity to alleviate hangovers;
  • Jay Thangappan, from Silvi Rouskin’s lab, who spoke about the importance of RNA structure in splicing and its consequences for many important biological processes;
  • Lindsey Backman, from Catherine Drennan’s lab, who spoke about the biochemical processes carried out by gut bacteria that make poop smell bad; and
  • Arish Shah, from Eliezer Calo’s lab, who spoke about how developing zebrafish clear maternally-contributed molecules and replace them with their own, thus becoming “independent from mom.”

The event was moderated by former Slammers, postdoc Monika Avello and graduate student Emma Kowal. The duo joined forces with the Building 68 communications team and Biology Graduate Student Council to publicize the event and host two pre-slam workshops and a practice session.

Kowal, last year’s winner, was motivated to mentor this year’s cohort because, as she puts it, most scientists either don’t recognize the importance of clear communication or don’t recognize the challenge of doing it well.

“It is rare to see graduate programs devote training time to this,” she says, “but I believe it’s worth the effort. Taking the time to distill what excites and motivates us in our research not only inspires people to value science and even become scientists, but also helps us connect with each other — and remember why we love doing science in the first place.”

Avello recalls signing up for last year’s slam at the last minute, and “loving the experience.”

“I wanted to facilitate the experience of thinking hard about science communication in a fun and inclusive way for other graduate students and postdocs,” she says. “I really enjoyed watching everyone wrestle with the challenge of presenting their science in such a tight, condensed format, and ultimately developing their own unique story and style.”

There were two prizes, one awarded by the three judges and another awarded by the audience. Silberman, a fifth-year graduate student whose talk was titled “Does Chromosome Imbalance Cause Cancer?,” took home the Judges’ Prize, while third-year graduate student Sophia Xu claimed the Audience Prize with her talk, “Plant Natural Products and Human Ethanol Metabolism.”

Silberman said her favorite part was watching her fellow participants’ talks develop over time during the consecutive practice sessions. “Getting the opportunity to workshop my ideas and get input from Emma, Moni, and the other participants made the final presentation much less terrifying than it would have been otherwise, and made my talk much better,” she says.

Xu saw the Slam as an opportunity to practice presenting her research in an engaging way, and take a small step toward conquering her fear of public speaking. “I was overwhelmed by the support I received, not only from the organizers, but also from the other speakers,” she says. “It felt much like what I imagine a collaborative, friendly British cooking show would be like.”

Silberman encourages Department of Biology trainees considering participating in next year’s slam to “go for it.” She adds: “As grad students, we often aren’t challenged to distill our research down to its simplest terms. It was both harder and more fun than I expected.”

The fluid that feeds tumor cells

The substance that bathes tumors in the body is quite different from the medium used to grow cancer cells in the lab, biologists report.

Anne Trafton | MIT News Office
April 16, 2019

Before being tested in animals or humans, most cancer drugs are evaluated in tumor cells grown in a lab dish. However, in recent years, there has been a growing realization that the environment in which these cells are grown does not accurately mimic the natural environment of a tumor, and that this discrepancy could produce inaccurate results.

In a new study, MIT biologists analyzed the composition of the interstitial fluid that normally surrounds pancreatic tumors, and found that its nutrient composition is different from that of the culture medium normally used to grow cancer cells. It also differs from blood, which feeds the interstitial fluid and removes waste products.

The findings suggest that growing cancer cells in a culture medium more similar to this fluid could help researchers better predict how experimental drugs will affect cancer cells, says Matthew Vander Heiden, an associate professor of biology at MIT and a member of the Koch Institute for Integrative Cancer Research.

“It’s kind of an obvious statement that the tumor environment is important, but I think in cancer research the pendulum had swung so far toward genes, people tended to forget that,” says Vander Heiden, one of the senior authors of the study.

Alex Muir, a former Koch Institute postdoc who is now an assistant professor at the University of Chicago, is also a senior author of the paper, which appears in the April 16 edition of the journal eLife. The lead author of the study is Mark Sullivan, an MIT graduate student.

Environment matters

Scientists have long known that cancer cells metabolize nutrients differently than most other cells. This alternative strategy helps them to generate the building blocks they need to continue growing and dividing, forming new cancer cells. In recent years, scientists have sought to develop drugs that interfere with these metabolic processes, and one such drug was approved to treat leukemia in 2017.

An important step in developing such drugs is to test them in cancer cells grown in a lab dish. The growth medium typically used to grow these cells includes carbon sources (such as glucose), nitrogen, and other nutrients. However, in the past few years, Vander Heiden’s lab has found that cancer cells grown in this medium respond differently to drugs than they do in mouse models of cancer.

David Sabatini, a member of the Whitehead Institute and professor of biology at MIT, has also found that drugs affect cancer cells differently if they are grown in a medium that resembles the nutrient composition of human plasma, instead of the traditional growth medium.

“That work, and similar results from a couple of other groups around the world, suggested that environment matters a lot,” Vander Heiden says. “It really was a wake up call for us that to really know how to find the dependencies of cancer, we have to get the environment right.”

To that end, the MIT team decided to investigate the composition of interstitial fluid, which bathes the tissue and carries nutrients that diffuse from blood flowing through the capillaries. Its composition is not identical to that of blood, and in tumors, it can be very different because tumors often have poor connections to the blood supply.

The researchers chose to focus on pancreatic cancer in part because it is known to be particularly nutrient-deprived. After isolating interstitial fluid from pancreatic tumors in mice, the researchers used mass spectrometry to measure the concentrations of more than 100 different nutrients, and discovered that the composition of the interstitial fluid is different from that of blood (and from that of the culture medium normally used to grow cells). Several of the nutrients that the researchers found to be depleted in tumor interstitial fluid are amino acids that are important for immune cell function, including arginine, tryptophan, and cystine.

Not all nutrients were depleted in the interstitial fluid — some were more plentiful, including the amino acids glycine and glutamate, which are known to be produced by some cancer cells.

Location, location, location

The researchers also compared tumors growing in the pancreas and the lungs and found that the composition of the interstitial fluid can vary based on tumors’ location in the body and at the site where the tumor originated. They also found slight differences between the fluid surrounding tumors that grew in the same location but had different genetic makeup; however, the genetic factors tested did not have as big an impact as the tumor location.

“That probably says that what determines what nutrients are in the environment is heavily driven by interactions between cancer cells and noncancer cells within the tumor,” Vander Heiden says.

Scientists have previously discovered that those noncancer cells, including supportive stromal cells and immune cells, can be recruited by cancer cells to help remake the environment around the tumor to promote cancer survival and spread.

Vander Heiden’s lab and other research groups are now working on developing a culture medium that would more closely mimic the composition of tumor interstitial fluid, so they can explore whether tumor cells grown in this environment could be used to generate more accurate predictions of how cancer drugs will affect cells in the body.

The research was funded by the National Institutes of Health, the Lustgarten Foundation, the MIT Center for Precision Cancer Medicine, Stand Up to Cancer, the Howard Hughes Medical Institute, and the Ludwig Center at MIT.

The evolving definition of a gene

Professor Gerald Fink, a pioneer in the field of genetics, delivers the annual Killian Lecture.

MIT News Office
April 8, 2019

More than 50 years ago, scientists came up with a definition for the gene: a sequence of DNA that is copied into RNA, which is used as a blueprint for assembling a protein.

In recent years, however, with the discovery of ever more DNA sequences that play key roles in gene expression without being translated into proteins, this simple definition needed revision, according to Gerald Fink, the Margaret and Herman Sokol Professor in Biomedical Research and American Cancer Society Professor of Genetics in MIT’s Department of Biology.

Fink, a pioneer in the field of genetics, discussed the evolution of this definition during yesterday’s James R. Killian Jr. Faculty Achievement Award Lecture, titled, “What is a Gene?”

“In genetics, we’ve lost a simple definition of the gene — a definition that lasted over 50 years,” he said. “But loss of the definition has spawned whole new fields trying to understand the unknown information in non-protein-coding DNA.”

Established in 1971 to honor MIT’s 10th president, James Killian, the Killian Award recognizes extraordinary professional achievements by an MIT faculty member. Fink, who is also a member and former director of the Whitehead Institute, was honored for his achievements in developing brewer’s yeast as “the premier model for understanding the biology of eukaryotes” — organisms whose cells have nuclei.

“He is among the very few scientists who can be singularly credited with fundamentally changing the way we approach biological problems,” says the award citation, read by Susan Silbey, chair of the MIT faculty, who presented Fink with the award.

Genetic revolution

Growing in a “sleepy” town on Long Island, Fink had a keen interest in science, which spiked after the Soviets launched the first satellite to orbit the Earth.

“In 1957, when I went out in our backyard, I was hypnotized by the new star in the sky, as Sputnik slowly raced toward the horizon,” he said. “Overnight, science became a national priority, energized by the dread of Soviet technology and technological superiority.”

After earning his bachelor’s degree at Amherst College, Fink began studying yeast as a graduate student at Yale University, and in 1976, he developed a way to insert any DNA sequence into yeast cells.

This discovery transformed biomedical research by allowing scientists to program yeast to produce any protein they wanted, as long as they knew the DNA sequence of the gene that encoded it. It also proved industrially useful: More than half of all therapeutic insulin is now produced by yeast, along with many other drugs and vaccines, as well as biofuels such as ethanol.

At that time, scientists were operating with a straightforward definition of the gene, based on the “central dogma” of biology: DNA makes RNA, and RNA makes proteins. Therefore, a gene was defined as a sequence of DNA that could code for a protein. This was convenient because it allowed computers to be programmed to search the genome for genes by looking for specific DNA sequences bracketed by codons that indicate the starting and stopping points of a gene.

In recent decades, scientists have done just that, identifying about 20,000 protein-coding genes in the human genome. They have also discovered genetic mechanisms involved in thousands of human diseases. Using new tools such as CRISPR, which enables genome editing, cures for such diseases may soon be available, Fink believes.

“The definition of a gene as a DNA sequence that codes for a protein, coupled with the sequencing of the human genome, has revolutionized molecular medicine,” he said. “Genome sequencing, along with computational power to compare and analyze genomes, has led to important insights into basic science and disease.”

However, he pointed out, protein-coding genes account for just 2 percent of the entire human genome. What about the rest of it? Scientists have traditionally referred to the remaining 98 percent as “junk DNA” that has no useful function.

In the 1980s, Fink began to suspect that this junk DNA was not as useless as had been believed. He and others discovered that in yeast, certain segments of DNA could “jump” from one location to another, and that these segments appeared to regulate the expression of whatever genes were nearby. This phenomenon was later observed in human cells as well.

“That alerted me and others to the fact that ‘junk DNA’ might be making RNA but not proteins,” Fink said.

Since then, scientists have discovered many types of non-protein-coding RNA molecules, including microRNAs, which can block the production of proteins, and long non-coding RNAs (lncRNAs), which have many roles in gene regulation.

“In the last 15 years, it has been found that these are critical for controlling the gene expression of protein-coding genes,” Fink said. “We’re only now beginning to visualize the importance of this formerly invisible part of the genome.”

Such discoveries demonstrate that the traditional definition of a gene is inadequate to encompass all of the information stored in the genome, he said.

“The existence of these diverse classes of RNA is evidence that there is no single physical and functional unit of heredity that we can call the gene,” he said. “Rather, the genome contains many different categories of informational units, each of which may be considered a gene.”

“A community of scholars”

In selecting Fink for the Killian Award, the award committed also cited his contributions to the founding of the Whitehead Institute, which opened in 1982. At the time, forming a research institute that was part of MIT yet also its own entity was considered a “radical experiment,” Fink recalled.

Though controversial at the time, with heated debate among the faculty, establishing the Whitehead Institute laid the groundwork for many other research institutes that have been established at MIT, and also helped to attract biotechnology companies to the Kendall Square area, Fink said.

“As we now know, MIT made the right decision. The Whitehead turned out to be a successful pioneer experiment that in my opinion led to the blossoming of the Kendall Square area,” he said.

Fink was hired as one of the first faculty members of the Whitehead Institute, and served as its director from 1990 to 2001, when he oversaw the Whitehead’s contributions to the Human Genome Project. He recalled that throughout his career, he has collaborated extensively not only with other biologists, but with MIT colleagues in fields such as physics, chemical engineering, and electrical engineering and computer science.

“MIT is a community of scholars, and I was welcomed into the community,” he said.

School of Science announces 2019 Infinite Mile Awards

Ten staff members in the School of Science are recognized for going above and beyond their job descriptions to support a better Institute.

School of Science
April 2, 2019

The MIT School of Science has announced the winners of the 2019 Infinite Mile Award, which is presented annually to staff members within the school who demonstrate exemplary dedication to making MIT a better place.

Nominated by their colleagues, these winners are notable for their unrelenting and extraordinary hard work in their positions, which can include mentoring fellow community members, innovating new solutions to problems big and small, building their communities, or going far above and beyond their job descriptions to support the goals of their home departments, labs, and research centers.

The 2019 Infinite Mile Award winners are:

Christine Brooks, an administrative assistant in the Department of Chemistry, nominated by Mircea Dincă and several members of the Dincă, Schrock, and Cummins groups;

Annie Cardinaux, a research specialist in the Department of Brain and Cognitive Sciences, nominated by Pawan Sinha;

Kimberli DeMayo, a human resources consultant in the Department of Mathematics, nominated by Nan Lin, Dennis Porche, and Paul Seidel, with support from several other faculty members;

Arek Hamalian, a technical associate at the Picower Institute for Learning and Memory, nominated by Susumu Tonegawa;

Jonathan Harmon, an administrative assistant in the Department of Mathematics, nominated by Pavel Etingof and Kimberli DeMayo, with support from several other faculty members;

Tanya Khovanova, a lecturer in the Department of Mathematics, nominated by Pavel Etingof, David Jerison, and Slava Gerovitch;

Kelley Mahoney, an SRS financial staff member in the Kavli Institute for Astrophysics and Space Research, nominated by Sarah Brady, Michael McDonald, Anna Frebel, Jacqueline Hewitt, Jack Defandorf, and Stacey Sullaway;

Walter Massefski, the director of instrumentation facility in the Department of Chemistry, nominated by Timothy Jamison and Richard Wilk;

Raleigh McElvery, a communications coordinator in the Department of Biology, nominated by Vivian Siegel with support from Amy Keating, Julia Keller, and Erika Reinfeld; and

Kate White, an administrative officer in the Department of Brain and Cognitive Sciences, nominated by Jim DiCarlo, Michale Fee, Sara Cody-Larnard, Rachel Donahue, Federico Chiavazza, Matthew Regan, Gayle Lutchen, and William Lawson.

The recipients will receive a monetary award in addition to being honored at a celebratory reception, along with their peers, family and friends, and the recipients of the 2019 Infinite Kilometer Award this month.

Biologists find a way to boost intestinal stem cell populations

Study suggests that stimulating stem cells may protect the gastrointestinal tract from age-related disease.

Anne Trafton | MIT News Office
March 28, 2019

Cells that line the intestinal tract are replaced every few days, a high rate of turnover that relies on a healthy population of intestinal stem cells. MIT and University of Tokyo biologists have now found that aging takes a toll on intestinal stem cells and may contribute to increased susceptibility to disorders of the gastrointestinal tract.

The researchers also showed that they could reverse this effect in aged mice by treating them with a compound that helps boost the population of intestinal stem cells. The findings suggest that this compound, which appears to stimulate a pathway that involves longevity-linked proteins known as sirtuins, could help protect the gut from age-related damage, the researchers say.

“One of the issues with aging is organ dysfunction, accompanied by a decline in the activity of the stem cells that nurture and replenish that organ, so this is a potentially very useful intervention point to either slow or reverse aging,” says Leonard Guarente, the Novartis Professor of Biology at MIT.

Guarente and Toshimasa Yamauchi, a professor at the University of Tokyo, are the senior authors of the study, which appears online in the journal Aging Cell on March 28. The lead author of the paper is Masaki Igarashi, a former MIT postdoc who is now at the University of Tokyo.

Population growth

Guarente’s lab has long studied the link between aging and sirtuins, a class of proteins found in nearly all animals. Sirtuins, which have been shown to protect against the effects of aging, can also be stimulated by calorie restriction.

In a paper published in 2016, Guarente and Igarashi found that in mice, low-calorie diets activate sirtuins in intestinal stem cells, helping the cells to proliferate. In their new study, they set out to investigate whether aging contributes to a decline in stem cell populations, and whether that decline could be reversed.

By comparing young (aged 3 to 5 months) and older (aged 2 years) mice, the researchers found that intestinal stem cell populations do decline with age. Furthermore, when these stem cells are removed from the mice and grown in a culture dish, they are less able to generate intestinal organoids, which mimic the structure of the intestinal lining, compared to stem cells from younger mice. The researchers also found reduced sirtuin levels in stem cells from the older mice.

Once the effects of aging were established, the researchers wanted to see if they could reverse the effects using a compound called nicotinamide riboside (NR). This compound is a precursor to NAD, a coenzyme that activates the sirtuin SIRT1. They found that after six weeks of drinking water spiked with NR, the older mice had normal levels of intestinal stem cells, and these cells were able to generate organoids as well as stem cells from younger mice could.

To determine if this stem cell boost actually has any health benefits, the researchers gave the older, NR-treated mice a compound that normally induces colitis. They found that NR protected the mice from the inflammation and tissue damage usually produced by this compound in older animals.

“That has real implications for health because just having more stem cells is all well and good, but it might not equate to anything in the real world,” Guarente says. “Knowing that the guts are actually more stress-resistant if they’re NR- supplemented is pretty interesting.”

Protective effects

Guarente says he believes that NR is likely acting through a pathway that his lab previously identified, in which boosting NAD turns on not only SIRT1 but another gene called mTORC1, which stimulates protein synthesis in cells and helps them to proliferate.

“What we would hypothesize is that the NAD replenishment in old mice is driving this pathway of growth that’s working through SIRT1 and TOR to reverse the decline that has occurred with aging,” he says.

The findings suggest that NAD might have a protective effect against diseases of the gut, such as colitis, in older people, he says. Guarente and his colleagues have previously found that NAD precursors can also stimulate the growth of blood vessels and muscles and boost endurance in aged mice, and a 2016 study from researchers in Switzerland found that boosting NAD can help replenish muscle stem cell populations in aged mice.

In 2014, Guarente started a company called Elysium Health, which sells a dietary supplement containing NR combined with another natural compound called pterostilbene, which is an activator of SIRT1.

The research was funded, in part, by the National Institutes of Health and the Glenn Foundation for Medical Research.

Whitehead Institute’s David Page to conclude term as director

Search committee chaired by MIT President Emerita Susan Hockfield will identify new director for eminent biomedical institute.

Lisa Girard | Whitehead Institute
March 27, 2019

Whitehead Institute, the world-renowned nonprofit research institution dedicated to improving human health through basic biomedical research, has announced that Institute Director David C. Page — a Whitehead Institute member since 1988 and director since 2004 — will complete his current term as director and president in summer 2020. An international search has been launched for Page’s successor.

“David’s tenure as director has been a period of incredible richness for Whitehead Institute,” says Charles D. Ellis, chair of the Whitehead Institute Board of Directors. “It has been rich in the path-breaking science that our researchers have done; in the intellectual ferment and creative environment that Whitehead members have fostered; and in the sense of community and common purpose that David has nurtured. He has led us with great skill and vision through a dynamic period of growth and continuous exploration, and he will pass to his successor an organization primed to tackle the challenges offered by a swiftly evolving bioscience landscape.”

Since its founding in 1982, Whitehead Institute has been one of the world’s most influential biomedical research centers — producing a continual stream of significant discoveries and new research tools and approaches. Whitehead Institute is a legally and financially independent organization closely affiliated with MIT, and Whitehead Institute members hold MIT faculty appointments. The 17 Whitehead Institute members include two National Medal of Science winners, nine National Academy of Sciences members, four National Academy of Medicine members, and four Investigators of the Howard Hughes Medical Institute. In addition, the institute’s prestigious Whitehead Fellows Program has fostered generations of biomedical science leaders — including Harvard Medical School Dean George Daley, celebrated MIT cancer researcher and professor of biology Angelika Amon, Broad Institute President and Founding Director Eric Lander, and NASA astronaut and space biologist Kate Rubins.

Whitehead Institute and MIT have been Page’s professional home since he earned an MD from Harvard Medical School and the Harvard-MIT Health Sciences and Technology Program and completed research in David Botstein’s lab at MIT in 1984. After serving as the institute’s first Whitehead Fellow, he became a Whitehead member and MIT faculty member in 1988. Page was appointed associate director of the institute in 2002, interim director in 2004, and director in 2005.

Throughout his 35 years at Whitehead Institute, Page has run a thriving and productive research lab. His groundbreaking studies on the Y chromosome changed the way biomedical science views the function of sex chromosomes. That work earned him wide recognition, including a Macarthur Foundation Fellowship and a Searle Scholar Award; and he has been an Investigator of the Howard Hughes Medical Institute since 1990. His research twice earned inclusion in Science magazine’s “Top 10 Breakthroughs of the Year,” first for mapping a human chromosome and then for sequencing the human Y chromosome. Today, his lab is pursuing a deep understanding of the role of sex chromosomes in health and disease — work with the potential to fundamentally change the practice of medicine and improve the quality of care for women and men alike.

As director, Page has made a mark on all facets of the Whitehead Institute organization. During his tenure, he oversaw the creation of the Institute’s Intellectual Property Office; strengthened its core facilities; and established new platforms, such as the Metabolomics Center. He also enhanced the leadership structure by appointing three associate directors; and he supported the creation of the child care center. Perhaps most important for the long run, Page has guided a robust renewal of faculty and has helped to prepare the organization for the eventual retirement of the Institute’s founding generation of members.

The search for Page’s successor will be guided by a committee of noted leaders in education, biomedical research, and nonprofit organizations, including Susan Hockfield (chair), MIT professor of neuroscience and president emerita; Laurie H. Glimcher, president and CEO of the Dana-Farber Cancer Institute and former dean of Weill Cornell Medical College; Alan Grossman, the Praecis Professor of Biology and head of the MIT Department of Biology; Paul L. Joskow, former president and CEO of Alfred P. Sloan Foundation and the Elizabeth and James Killian Professor of Economics Emeritus at MIT; Amy E. Keating, professor in the departments of Biology and Biological Engineering at MIT; David Sabatini, Whitehead Institute member and associate director, and professor of biology at MIT; Phillip A. Sharp, Nobel laureate and MIT Institute professor and professor of biology; and Sarah Williamson, CEO of FCLT Global and former partner at Wellington Management Company (Joskow, Sharp, and Williamson are also members of the Whitehead Institute Board of Directors.)

The committee will be assisted by global executive search firm Russell Reynolds Associates.

“Whitehead Institute is one of the world’s premier research institutions,” says Hockfield. “It possesses an innovative and collaborative culture; rich talent and intellectual capital; a robust relationship with MIT; and a place at the heart of the Kendall Square innovation community. These factors make it an ideal opportunity for a director with vision, scientific courage, and a passion to address basic biomedical science’s most significant challenges.”

“The scientists of Whitehead Institute have helped to drive biomedical research forward and onto exciting new paths,” says Page. “In coming years, the Institute itself will experience a generational evolution, and my successor will help define the organization’s future — and by extension, help shape the direction of biomedical research for decades to come.”

The new director will have an impressive line of predecessors: Whitehead Institute’s founding director was Nobel laureate and former Caltech president David Baltimore; he was succeeded by globally respected researcher and science enterprise leader Gerald Fink, and then by National Medal of Science recipient Susan Lindquist — Page’s immediate predecessor.

Alana gift to MIT launches Down syndrome research center, technology program for disabilities

Foundation’s $28.6 million gift will fund science, innovation, and education to advance understanding, ability, and inclusion.

David Orenstein | Picower Institute for Learning and Memory
March 21, 2019

As part of its continued mission to help build a better world, MIT is establishing the Alana Down Syndrome Center, an innovative new research endeavor, technology development initiative, and fellowship program launched with a $28.6 million gift from Alana Foundation, a nonprofit organization started by Ana Lucia Villela of São Paulo, Brazil.

In addition to multidisciplinary research across neuroscience, biology, engineering, and computer science labs, the gift will fund a four-year program with MIT’s Deshpande Center for Technological Innovation called “Technology to Improve Ability,” in which creative minds around the Institute will be encouraged and supported in designing and developing technologies that can improve life for people with different intellectual abilities or other challenges.

The Alana Down Syndrome Center, based out of MIT’s Picower Institute for Learning and Memory, will engage the expertise of scientists and engineers in a research effort to increase understanding of the biology and neuroscience of Down syndrome. The center will also provide new training and educational opportunities for early career scientists and students to become involved in Down syndrome research. Together, the center and technology program will work to accelerate the generation, development, and clinical testing of novel interventions and technologies to improve the quality of life for people with Down syndrome.

“At MIT, we value frontier research, particularly when it is aimed at making a better world,” says MIT President L. Rafael Reif. “The Alana Foundation’s inspiring gift will position MIT’s researchers to investigate new pathways to enhance and extend the lives of those with Down syndrome. We are grateful to the foundation’s leadership — President Ana Lucia Villela and Co-President Marcos Nisti — for entrusting our community with this critical challenge.”

With a $1.7 million gift to MIT in 2015, Alana funded studies to create new laboratory models of Down syndrome and to improve understanding of the mechanisms of the disorder and potential therapies. In creating the new center, MIT and the Alana Foundation officials say they are building on that partnership to promote discovery and technology development aimed at helping people with different abilities gain greater social and practical skills to enhance their participation in the educational system, in the workforce, and in community life.

“We couldn’t be happier and more hopeful as to the size of the impact this center can generate,” Villela says. “It’s an innovative approach that doesn’t focus on the disability but, instead, focuses on the barriers that can prevent people with Down syndrome from thriving in life in their own way.”

Marcos Nisti, co-president of Alana, adds, “This grant represents all the trust we have in MIT especially because the values our family hold are so aligned with MIT’s own values and its mission.”

Villela and Nisti have two daughters, one with Down syndrome. MIT Executive Vice President and Treasurer Israel Ruiz has had a personal connection to the foundation.

“It is an extraordinary day,” Ruiz says. “It has been a pleasure getting to know Ana Lucia, Marcos and their family over the past few years. Their work to advance the needs of the Down syndrome community is truly exemplary, and I look forward to future collaborations. Today, MIT celebrates their generosity in recognizing all abilities and working to provide opportunities to all.”

Down syndrome, also known as trisomy 21, is characterized by extra genetic material from some or all of chromosome 21 in many or all of an individual’s cells and occurs in one out of every 700 babies in the United States. Though the chromosomal hallmark of Down syndrome has been well known for decades, and advances in research, health care and social services have doubled lifespans over the past 25 years, significant challenges remain for individuals with different abilities and their families because the underlying neurobiology of the disorder is complex.

The center will be co-directed by Angelika Amon, the Kathleen and Curtis Marble Professor in Cancer Research, and Li-Huei Tsai, the Picower Professor of Neuroscience. Amon is an expert in understanding the health impacts of chromosomal instability and aneuploidy, the presence of an abnormal chromosome number, while Tsai is renowned for her work in the field of neurodegenerative disorders, including Alzheimer’s disease, which shares important underlying similarities with Down syndrome.

In the first four years, the new center will employ cutting-edge techniques to study Down syndrome in the brain with two main focuses: systems and circuits as well as genes and cells.

With the support of the previous Alana Foundation gift, Hiruy Meharena, senior fellow in Tsai’s neuroscience lab, has already been deeply engaged in studying Down syndrome’s impact in the brain at the cellular and genomic level, examining key differences in gene expression in cultures of neurons and glia created from patient-derived induced pluripotent stem cells.

To further advance research at that molecular scale, Tsai’s lab will collaborate with computer science Professor Manolis Kellis, director of MIT’s Computational Biology Group and a leader in creating sophisticated methods for big-data integration and analysis of genomic and gene expression data.

At the systems and circuits level, Ed Boyden, the Y. Eva Tan Professor in Neurotechnology will lead efforts to conduct high-resolution 3-D brain mapping and will collaborate with Tsai to examine the potential of using her emerging non-invasive, sensory-based therapy for Alzheimer’s in Down syndrome.

Amon’s lab will bring its deep expertise from their study of cancer to the new center. Researchers there have made important discoveries about how aneuploidy may undermine overall health, for instance by causing stresses within cells. It is their hope that identifying genetic alterations that suppress the stresses associated with trisomy 21 could lead to the development of therapeutics that improve cell function in individuals with Down syndrome.

To further support these research endeavors and to increase the long-term global pipeline of scientists trained in the study of Down syndrome, the Alana Down Syndrome Center will fund postdoctoral Alana Fellowships and graduate fellowships.

The Alana Center will also convene an annual symposium on Down syndrome research, the first of which is tentatively scheduled for this fall.

The Alana Foundation gift supports the MIT Campaign for a Better World, which was publicly launched in 2016 with a mission to advance MIT’s work in education, research, and innovation to address humanity’s urgent challenges. A joint statement guiding the gift’s purpose is available at alana.mit.edu/statement.

How tumors behave on acid

Acidic environment triggers genes that help cancer cells metastasize.

Anne Trafton | MIT News Office
March 21, 2019

Scientists have long known that tumors have many pockets of high acidity, usually found deep within the tumor where little oxygen is available. However, a new study from MIT researchers has found that tumor surfaces are also highly acidic, and that this acidity helps tumors to become more invasive and metastatic.

The study found that the acidic environment helps tumor cells to produce proteins that make them more aggressive. The researchers also showed that they could reverse this process in mice by making the tumor environment less acidic.

“Our findings reinforce the view that tumor acidification is an important driver of aggressive tumor phenotypes, and it indicates that methods that target this acidity could be of value therapeutically,” says Frank Gertler, an MIT professor of biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the study.

Former MIT postdoc Nazanin Rohani is the lead author of the study, which appears in the journal Cancer Research.

Mapping acidity

Scientists usually attribute a tumor’s high acidity to the lack of oxygen, or hypoxia, that often occurs in tumors because they don’t have an adequate blood supply. However, until now, it has been difficult to precisely map tumor acidity and determine whether it overlaps with hypoxic regions.

In this study, the MIT team used a probe called pH (Low) Insertion Peptide (pHLIP), originally developed by researchers at the University of Rhode Island, to map the acidic regions of breast tumors in mice. This peptide is floppy at normal pH but becomes more stable at low, acidic pH. When this happens, the peptide can insert itself into cell membranes. This allows the researchers to determine which cells have been exposed to acidic conditions, by identifying cells that have been tagged with the peptide.

To their surprise, the researchers found that not only were cells in the oxygen-deprived interior of the tumor acidic, there were also acidic regions at the boundary of the tumor and the structural tissue that surrounds it, known as the stroma.

“There was a great deal of tumor tissue that did not have any hallmarks of hypoxia that was quite clearly exposed to acidosis,” Gertler says. “We started looking at that, and we realized hypoxia probably wouldn’t explain the majority of regions of the tumor that were acidic.”

Further investigation revealed that many of the cells at the tumor surface had shifted to a type of cell metabolism known as aerobic glycolysis. This process generates lactic acid as a byproduct, which could account for the high acidity, Gertler says. The researchers also discovered that in these acidic regions, cells had turned on gene expression programs associated with invasion and metastasis. Nearly 3,000 genes showed pH-dependent changes in activity, and close to 300 displayed changes in how the genes are assembled, or spliced.

“Tumor acidosis gives rise to the expression of molecules involved in cell invasion and migration. This reprogramming, which is an intracellular response to a drop in extracellular pH, gives the cancer cells the ability to survive under low-pH conditions and proliferate,” Rohani says.

Those activated genes include Mena, which codes for a protein that normally plays a key role in embryonic development. Gertler’s lab had previously discovered that in some tumors, Mena is spliced differently, producing an alternative form of the protein known as MenaINV (invasive). This protein helps cells to migrate into blood vessels and spread though the body.

Another key protein that undergoes alternative splicing in acidic conditions is CD44, which also helps tumor cells to become more aggressive and break through the extracellular tissues that normally surround them. This study marks the first time that acidity has been shown to trigger alternative splicing for these two genes.

Reducing acidity

The researchers then decided to study how these genes would respond to decreasing the acidity of the tumor microenvironment. To do that, they added sodium bicarbonate to the mice’s drinking water. This treatment reduced tumor acidity and shifted gene expression closer to the normal state. In other studies, sodium bicarbonate has also been shown to reduce metastasis in mouse models.

Sodium bicarbonate would not be a feasible cancer treatment because it is not well-tolerated by humans, but other approaches that lower acidity could be worth exploring, Gertler says. The expression of new alternative splicing genes in response to the acidic microenvironment of the tumor helps cells survive, so this phenomenon could be exploited to reverse those programs and perturb tumor growth and potentially metastasis.

“Other methods that would more focally target acidification could be of great value,” he says.

The research was funded by the Koch Institute Support (core) Grant from the National Cancer Institute, the Howard Hughes Medical Institute, the National Institutes of Health, the KI Quinquennial Cancer Research Fellowship, and MIT’s Undergraduate Research Opportunities Program.

Other authors of the paper include Liangliang Hao, a former MIT postdoc; Maria Alexis and Konstantin Krismer, MIT graduate students; Brian Joughin, a lead research modeler at the Koch Institute; Mira Moufarrej, a recent graduate of MIT; Anthony Soltis, a recent MIT PhD recipient; Douglas Lauffenburger, head of MIT’s Department of Biological Engineering; Michael Yaffe, a David H. Koch Professor of Science; Christopher Burge, an MIT professor of biology; and Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science.

Meenakshi Chakraborty named 2019 Churchill Scholar

Senior majoring in computer science and molecular biology will pursue an MPhil at Cambridge University.

Office of Distinguished Fellowships
March 18, 2019

Meenakshi Chakraborty, a senior from Cambridge, Massachusetts, has been named a 2019 Churchill Scholar and will pursue an MPhil at Cambridge University.

Chakraborty is expected to graduate this spring with a BS in computer science and molecular biology. As a Churchill scholar she aims to pursue a master’s degree in genetics at Cambridge. When she returns to the U.S. she plans to pursue a PhD in biology with a focus on genetics.

Chakraborty realized a passion for scientific research when still in high school. After a trip to a South African hospital, she realized the devastation caused by the AIDS epidemic, and discovered a desire to participate in scientific research that could lead to medical breakthroughs. Upon her return, she learned of the work of Bruce Walker, director of the Ragon Institute of MGH, MIT, and Harvard, and a professor at MIT’s Institute for Medical Engineering and Science. Despite the fact that Chakraborty was still in high school, Walker agreed to mentor her work on a study of epidemiology of HIV.

Chakraborty next began research under the tutelage of Institute Professor Phil Sharp. Jeremy Wilusz, a former Sharp Lab postdoc and current professor of biochemistry at the University of Pennsylvania, says, “It was clear long ago that Meena was a superstar in the making. As a 15-year-old, she reached out to Phil about writing an independent report on RNA over the summer. (I believe you had to be at least 16 to do actual research in a lab at MIT, so this was her way of getting her feet wet.) She asked to meet with one of the postdocs in the lab every couple of weeks to make sure she was heading in the right direction, and I became that postdoc. We decided to have her write a report on the history and functions of circular RNAs, which had recently been the subject of several prominent papers in Nature. She would go off, read a ton of papers, write extensive outlines, and bring very thoughtful questions to my attention that we would talk about. This effort ultimately resulted in the first Wikipedia page on circular RNAs (completely her idea) that others have built upon as the field has evolved.”

When Chakraborty matriculated at MIT, she began conducting research in the Sharp Lab at the Koch Institute for Integrative Cancer Research, as an Undergraduate Research Opportunities Program (UROP) student. During her time in the lab, she has investigated cell states, and how cells with identical genetic information and the same differentiation state vary. This issue is at the center of problems in developmental biology and the mechanisms of cancer. She has worked closely with research scientist Salil Garg on this work, who says, “Meena makes everything around her more fun. Her endless enthusiasm and positivity rub off on everyone in lab. Working with her has been an absolute joy. It’s hard to imagine what the lab will be like without her.”

Chakraborty has also participated in competitive summer research programs including MIT’s Johnson and Johnson UROP Scholars Program, which aims to support and increase the number of women in STEM, manufacturing, and design fields. With funding from Johnson and Johnson as part of its Women in Science, Technology, Engineering, Math, Manufacturing and Design (WiSTEM2D) initiative, Johnson and Johnson UROP Scholars conduct full-time summer research, in addition to attending faculty presentations, workshops, and networking events. Sarah Nelson, senior program coordinator of UROP and Johnson and Johnson UROP Scholars, says, “Meena was a great addition to this program not only because she is an outstanding student and researcher, but she is a true advocate for women in STEM.”

Chakraborty received a Goldwater scholarship last year due to her exceptional work as a student and researcher. She has continued to work in the Sharp lab while she finishes her degree at MIT.

During her time at MIT, she has also worked on science advocacy with MIT Effective Altruism (EA) Club. Chakraborty plans to explore working with Cambridge EA while studying in the U.K. She hopes to use this opportunity to develop her multidisciplinary approach to research and developing treatments for life-threatening conditions.

Chakraborty was advised in her application by Kim Benard in the Office of Distinguished Fellowships and by the Presidential Committee for Distinguished Fellowships, co-chaired by Professors William Broadhead and Rebecca Saxe. The Churchill Scholarship is a competitive program that annually offers 16 students an opportunity to pursue a funded graduate degree in science, mathematics or engineering at Churchill College within Cambridge University.

Committed to service and science

When senior Julia Ginder isn’t investigating the mystery of her own allergies, she’s volunteering to help young people reach their goals.

Gina Vitale | MIT News correspondent
February 25, 2019

Julia Ginder has to avoid a lot of foods due to allergies. From a young age, she got used to bringing her own snacks to birthday parties and group outings. But she didn’t really know the science behind her allergies until high school, when she read a chapter for class on immunology.

“I read it, and then I read it again, and I went running downstairs to tell my mom, ‘This is what’s wrong with me!’” she recalls.

From them on, Ginder was driven to learn about what made her body react so severely to certain stimuli. Now a biology major, she does research in the lab of Christopher Love, in the Koch Institute for Integrative Cancer Research, where she studies peanut allergies — one of the few food allergies she actually doesn’t have.

“I really enjoy figuring out, what’s the perspective from the biology side? What is the contributing chemistry? And how do those fit together?” she says. “And then, when you take a step back, how do you use that knowledge and perhaps the technology that comes out of it, and actually apply that in the real world?”

Nuts about research

In the Love lab, researchers look at how individual immune cells from people with peanut allergies react when stimulated with peanut extracts. More recently, they’ve been analyzing how the stimulated cells change over the course of treatment, evolving from one state to the next.

“You can watch the activation signals change over time in individual cells from peanut-allergic patients compared to healthy ones,” Ginder explains. “You can then dig deeper and look at distinct populations of cells at a single time point. With all of this information, you can start to get a sense of what critical cell types and signals are making the allergic person maintain a reaction.”

The researchers aim to figure out which cell types are associated with the development of tolerance so that more effective treatments can be developed. For instance, allergic people are sometimes given peanuts in small doses as a sort of biological exposure therapy, but perhaps if more key cell states are identified, targeted drug treatments can be added on top of that to induce those cell states.

Further pursuing her interest in health, Ginder spent the Independent Activities Period of her sophomore year volunteering for Boston Medical Center. The program she worked for helped families learn how to be advocates for their children with autism. For instance, it provided guidance on how to negotiate an appropriate accommodations agreement with their child’s school for their individual needs.

“It [the BMC experience] made it clear to me that for a child to succeed, they need to have support from both the educational side and the health side,” she says. “And it might seem obvious, but, especially for a child who might be coming from a less privileged background, those are two really important angles for ensuring that they are given the opportunity to reach their full potential.”

“The most helpful thing you can do is simply be there.”

Ginder became a swim coach and tutor for Amphibious Achievement in the fall of her first year, almost immediately after arriving at MIT. It’s a program that aims to help high schoolers reach both their athletic and academic goals. The high schoolers, often known as Achievers, are assigned a mentor like Ginder who helps with the academic and the athletic activities.

Local students come to MIT early Sunday morning to practice swimming or rowing, head to the Maseeh dining hall for lunch, participate in an afternoon academics lesson, reflect on their goals, and then spend a half an hour one-on-one with their mentor. It’s a big commitment for both the Achievers and mentors to spend almost six hours every Sunday with the program, but Ginder, who completed her two-year term as one of the co-executive directors this fall, has seen the importance of showing up week after week.

“The most helpful thing you can do is simply be there. Listen if they want to tell you anything, but really just being consistent — every single Sunday, being there.”

Ginder played on the field hockey team during her first year. However, when a practice during her sophomore year left her with a concussion and unable to play, she used the newfound spare time to start volunteering for Camp Kesem (CK). Having really enjoyed her experience at Amphibious Achievement, she was eager to be a counselor for the camp, which serves children whose parents are affected by cancer.

“Being there for someone, whether they are having a tough time or a great day, is really important to me. I felt that CK really aligned with that value I hold, and I hoped to meet even more people at MIT who felt that way. And so I joined, and I’ve loved it,” she says.

Management and moving west

Eventually, Ginder would like to become a physician, possibly in the fields of pediatrics and allergies. However, with a minor in public policy, she’s interested in developing areas outside of science as well. So, for the next couple of years, she’ll be moving westward to work as an associate consultant for Bain and Company in San Francisco.

“The reason I’m most interested in consulting is that there is this strong culture of learning and feedback. I want to improve my ability to be a strong team member, leader, and persuader. I think these are areas where I can continue to grow a lot,” she says. “It may sound silly, but I think for me, as someone who is 5’2” and hoping to become a pediatrician, it’s important to cultivate those professional skills early. I want to also serve as a leader and advocate outside of the clinic.”

As Ginder admits, the move is quite the geographic leap. Right now, her entire family is between a 20-minute and two-hour drive away. Moving to the opposite side of the country will be difficult, but she isn’t one to shy away from a challenge.

“I think it’ll be a bit sad because I’m not going to be as close to my family, but I think that it’ll really push me to be as independent as possible. I’ll need to look for my own opportunities, meet new people, build my network, and be my own person,” she says. “I’m really excited about that.”