Research Area: Immunology

Department of Biology hosts its first Science Slam

Eight biology trainees had just three minutes to explain their research and earn favor with the judges and audience in new yearly event.

Raleigh McElvery | Department of Biology
October 5, 2017

Nearly 300 spectators crowded into a lecture hall at the Ray and Maria Stata Center on a recent Tuesday to witness the first annual Science Slam, hosted by MIT’s Department of Biology.

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. The 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 jury included Ellen Clegg, editorial page editor of The Boston Globe and co-author of two award-winning books, “ChemoBrain” and “The Alzheimer’s Solution;” Emilie Marcus, CEO of Cell Press and editor-in-chief of the flagship journal, Cell; and Ari Daniel, an independent science reporter who produces digital videos for PBS NOVA and co-produces the Boston branch of Story Collider.

Among the competitors were five graduate students and three postdocs who hailed from labs scattered throughout Building 68, the Whitehead Institute, the Broad Institute, the Koch Institute for Integrative Cancer Research, and the Picower Institute for Learning and Memory. The storytellers were:

  • Sahin Naqvi, from David Page’s lab, who spoke about the evolution of genetic sex differences in mammals, as well as how these differences impact the likelihood of developing certain diseases based on gender;
  • Sudha Kumari, from Darrell Irvine’s lab, who spoke about her work investigating immune cell interactions — specifically how T cells communicate using physical contact;
  • Deniz Atabay, from Peter Reddien’s lab, who spoke about the ways cells in flatworms self-organize during regeneration to re-form organs, tissues, and even neural circuits;
  • Emma Kowal, from Christopher Burge’s lab, who spoke about her goals to demystify the ways in which certain noncoding regions of genetic sequence, known as introns, contribute to protein production;
  • Xin Tang, from Rudolf Jaenisch’s lab, who spoke about a technique to illuminate the seemingly invisible changes in brain cells that trigger disease, using a glowing enzyme from a firefly;
  • Nicole Aponte, from Troy Littleton’s lab, who spoke about her ability to manipulate brain cell activity in the fruit fly, and study how defects in neuronal connections contribute to developmental disorders;
  • Karthik Shekhar, from Aviv Regev’s lab, who spoke about his efforts to identify and manipulate different types of brain cells, understanding how they assemble into complex networks to facilitate learning, memory, and — in some cases — disease; and
  • Monika Avello, from Alan Grossman’s lab, who spoke about “bacterial sexology,” that is, how and why these organisms choose to block unwanted sexual advances from fellow bacteria.

Vivian Siegel, who oversees the department’s communications efforts, moderated the event. Siegel and the Building 68 communications team joined forces with three members of the Building 68 MIT Postdoctoral Association — Ana Fiszbein, Isabel Nocedal, and Peter Sudmant — to publicize the event and to host two pre-slam workshops, as well as one-on-one training sessions with individual participants.

“Participating in a Science Slam seemed like a great way for our trainees to learn how to communicate to a nonspecialized audience, which is something they will need to be able to do throughout their careers,” Siegel said. “We really wanted to develop a camaraderie among the participants, and bring trainees together from across the department to help each other tell compelling stories about their science.”

Kowal — whose talk was titled “Gone but Not Forgotten: How Do Introns Enhance Gene Expression?”  — ultimately took home both the audience and jury cash prizes. Kowal completed her undergraduate degree in chemical and physical biology at Harvard before coming to MIT for graduate school. Her dream is to write science fiction, so she decided she’d better study science so she’d know what to write about.

“I really enjoyed seeing people get stoked about introns, and the fact that they enhance gene expression,” she said. “It’s a great way to get comfortable explaining your project in a compelling way to a broad audience. Since you’ll probably be telling people about your work for a while, I think it’s a very good use of time to practice doing that.”

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.”

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.