Author: mantulin

Why cancer cells waste so much energy

MIT study sheds light on the longstanding question of why cancer cells get their energy from fermentation.

Anne Trafton | MIT News Office
January 19, 2021

In the 1920s, German chemist Otto Warburg discovered that cancer cells don’t metabolize sugar the same way that healthy cells usually do. Since then, scientists have tried to figure out why cancer cells use this alternative pathway, which is much less efficient.

MIT biologists have now found a possible answer to this longstanding question. In a study appearing in Molecular Cell, they showed that this metabolic pathway, known as fermentation, helps cells to regenerate large quantities of a molecule called NAD+, which they need to synthesize DNA and other important molecules. Their findings also account for why other types of rapidly proliferating cells, such as immune cells, switch over to fermentation.

“This has really been a hundred-year-old paradox that many people have tried to explain in different ways,” says Matthew Vander Heiden, an associate professor of biology at MIT and associate director of MIT’s Koch Institute for Integrative Cancer Research. “What we found is that under certain circumstances, cells need to do more of these electron transfer reactions, which require NAD+, in order to make molecules such as DNA.”

Vander Heiden is the senior author of the new study, and the lead authors are former MIT graduate student and postdoc Alba Luengo PhD ’18 and graduate student Zhaoqi Li.

Inefficient metabolism

Fermentation is one way that cells can convert the energy found in sugar to ATP, a chemical that cells use to store energy for all of their needs. However, mammalian cells usually break down sugar using a process called aerobic respiration, which yields much more ATP. Cells typically switch over to fermentation only when they don’t have enough oxygen available to perform aerobic respiration.

Since Warburg’s discovery, scientists have put forth many theories for why cancer cells switch to the inefficient fermentation pathway. Warburg originally proposed that cancer cells’ mitochondria, where aerobic respiration occurs, might be damaged, but this turned out not to be the case. Other explanations have focused on the possible benefits of producing ATP in a different way, but none of these theories have gained widespread support.

In this study, the MIT team decided to try to come up with a solution by asking what would happen if they suppressed cancer cells’ ability to perform fermentation. To do that, they treated the cells with a drug that forces them to divert a molecule called pyruvate from the fermentation pathway into the aerobic respiration pathway.

They saw, as others have previously shown, that blocking fermentation slows down cancer cells’ growth. Then, they tried to figure out how to restore the cells’ ability to proliferate, while still blocking fermentation. One approach they tried was to stimulate the cells to produce NAD+, a molecule that helps cells to dispose of the extra electrons that are stripped out when cells make molecules such as DNA and proteins.

When the researchers treated the cells with a drug that stimulates NAD+ production, they found that the cells started rapidly proliferating again, even though they still couldn’t perform fermentation. This led the researchers to theorize that when cells are growing rapidly, they need NAD+ more than they need ATP. During aerobic respiration, cells produce a great deal of ATP and some NAD+. If cells accumulate more ATP than they can use, respiration slows and production of NAD+ also slows.

“We hypothesized that when you make both NAD+ and ATP together, if you can’t get rid of ATP, it’s going to back up the whole system such that you also cannot make NAD+,” Li says.

Therefore, switching to a less efficient method of producing ATP, which allows the cells to generate more NAD+, actually helps them to grow faster. “If you step back and look at the pathways, what you realize is that fermentation allows you to generate NAD+ in an uncoupled way,” Luengo says.

Solving the paradox

The researchers tested this idea in other types of rapidly proliferating cells, including immune cells, and found that blocking fermentation but allowing alternative methods of NAD+ production enabled cells to continue rapidly dividing. They also observed the same phenomenon in nonmammalian cells such as yeast, which perform a different type of fermentation that produces ethanol.

“Not all proliferating cells have to do this,” Vander Heiden says. “It’s really only cells that are growing very fast. If cells are growing so fast that their demand to make stuff outstrips how much ATP they’re burning, that’s when they flip over into this type of metabolism. So, it solves, in my mind, many of the paradoxes that have existed.”

The findings suggest that drugs that force cancer cells to switch back to aerobic respiration instead of fermentation could offer a possible way to treat tumors. Drugs that inhibit NAD+ production could also have a beneficial effect, the researchers say.

The research was funded by the Ludwig Center for Molecular Oncology, the National Science Foundation, the National Institutes of Health, the Howard Hughes Medical Institute, the Medical Research Council, NHS Blood and Transplant, the Novo Nordisk Foundation, the Knut and Alice Wallenberg Foundation, Stand Up 2 Cancer, the Lustgarten Foundation, and the MIT Center for Precision Cancer Medicine.

Neuroscientists identify brain circuit that encodes timing of events

Findings suggest this hippocampal circuit helps us to maintain our timeline of memories.

Anne Trafton | MIT News Office
January 12, 2021

When we experience a new event, our brain records a memory of not only what happened, but also the context, including the time and location of the event. A new study from MIT neuroscientists sheds light on how the timing of a memory is encoded in the hippocampus, and suggests that time and space are encoded separately.

In a study of mice, the researchers identified a hippocampal circuit that the animals used to store information about the timing of when they should turn left or right in a maze. When this circuit was blocked, the mice were unable to remember which way they were supposed to turn next. However, disrupting the circuit did not appear to impair their memory of where they were in space.

The findings add to a growing body of evidence suggesting that when we form new memories, different populations of neurons in the brain encode time and place information, the researchers say.

“There is an emerging view that ‘place cells’ and ‘time cells’ organize memories by mapping information onto the hippocampus. This spatial and temporal context serves as a scaffold that allows us to build our own personal timeline of memories,” says Chris MacDonald, a research scientist at MIT’s Picower Institute for Learning and Memory and the lead author of the study.

Susumu Tonegawa, the Picower Professor of Biology and Neuroscience at the RIKEN-MIT Laboratory of Neural Circuit Genetics at the Picower Institute, is the senior author of the study, which appears this week in the Proceedings of the National Academy of Sciences.

Time and place

About 50 years ago, neuroscientists discovered that the brain’s hippocampus contains neurons that encode memories of specific locations. These cells, known as place cells, store information that becomes part of the context of a particular memory.

The other critical piece of context for any given memory is the timing. In 2011, MacDonald and the late Howard Eichenbaum, a professor of psychological and brain sciences at Boston University, discovered cells that keep track of time, in a part of the hippocampus called CA1.

In that study, MacDonald, who was then a postdoc at Boston University, found that these cells showed specific timing-related firing patterns when mice were trained to associate two stimuli — an object and an odor — that were presented with a 10-second delay between them. When the delay was extended to 20 seconds, the cells reorganized their firing patterns to last 20 seconds instead of 10.

“It’s almost like they’re forming a new representation of a temporal context, much like a spatial context,” MacDonald says. “The emerging view seems to be that both place and time cells organize memory by mapping experience to a representation of context that is defined by time and space.”

In the new study, the researchers wanted to investigate which other parts of the brain might be feeding CA1 timing information. Some previous studies had suggested that a nearby part of the hippocampus called CA2 might be involved in keeping track of time. CA2 is a very small region of the hippocampus that has not been extensively studied, but it has been shown to have strong connections to CA1.

To study the links between CA2 and CA1, the researchers used an engineered mouse model in which they could use light to control the activity of neurons in the CA2 region. They trained the mice to run a figure-eight maze in which they would earn a reward if they alternated turning left and right each time they ran the maze. Between each trial, they ran on a treadmill for 10 seconds, and during this time, they had to remember which direction they had turned on the previous trial, so they could do the opposite on the upcoming trial.

When the researchers turned off CA2 activity while the mice were on the treadmill, they found that the mice performed very poorly at the task, suggesting that they could no longer remember which direction they had turned in the previous trial.

“When the animals are performing normally, there is a sequence of cells in CA1 that ticks off during this temporal coding phase,” MacDonald says. “When you inhibit the CA2, what you see is the temporal coding in CA1 becomes less precise and more smeared out in time. It becomes destabilized, and that seems to correlate with them also performing poorly on that task.”

Memory circuits

When the researchers used light to inhibit CA2 neurons while the mice were running the maze, they found little effect on the CA1 “place cells” that allow the mice to remember where they are. The findings suggest that spatial and timing information are encoded preferentially by different parts of the hippocampus, MacDonald says.

“One thing that’s exciting about this work is this idea that spatial and temporal information can operate in parallel and might merge or separate at different points in the circuit, depending on what you need to accomplish from a memory standpoint,” he says.

MacDonald is now planning additional studies of time perception, including how we perceive time under different circumstances, and how our perception of time influences our behavior. Another question he hopes to pursue is whether the brain has different mechanisms for keeping track of events that are separated by seconds and events that are separated by much longer periods of time.

“Somehow the information that we store in memory preserves the sequential order of events across very different timescales, and I’m very interested in how it is that we’re able to do that,” he says.

The research was funded by the RIKEN Center for Brain Science, the Howard Hughes Medical Institute, and the JPB Foundation.

Turning microbiome research into a force for health

A diverse group of researchers is working to turn new discoveries about the trillions of microbes in the body into treatments for a range of diseases.

Zach Winn | MIT News Office
January 8, 2021

The microbiome comprises trillions of microorganisms living on and inside each of us. Historically, some researchers have guessed at its role in human health, but in the last decade or so genetic sequencing techniques have illuminated this galaxy of microorganisms enough to study it in detail.

As researchers unravel the complex interplay between our bodies and microbiomes, they are beginning to appreciate the full scope of the field’s potential for treating disease and promoting health.

For instance, the growing list of conditions that correspond with changes in the microbes of our gut includes type 2 diabetes, inflammatory bowel disease, Alzheimer’s disease, and a variety of cancers.

“In almost every disease context that’s been investigated, we’ve found different types of microbial communities, divergent between healthy and sick patients,” says professor of biological engineering Eric Alm. “The promise [of these findings] is that some of those differences are going to be causal, and intervening to change the microbiome is going to help treat some of these diseases.”

Alm’s lab, in conjunction with collaborators at the Broad Institute of MIT and Harvard, did some of the early work characterizing the gut microbiome and showing its relationship to human health. Since then, microbiome research has exploded, pulling in researchers from far-flung fields and setting new discoveries in motion. Startups are now working to develop microbiome-based therapies, and nonprofit organizations have also sprouted up to ensure these basic scientific advances turn into treatments that benefit the maximum number of people.

“The first chapter in this field, and our history, has been validating this modality,” says Mark Smith PhD ’14, a co-founder of OpenBiome, which processes stool donations for hospitals to conduct stool transplants for patients battling gut infection. Smith is also currently CEO of the startup Finch Therapeutics, which is developing microbiome-based treatments. “Until now, it’s been about the promise of the microbiome. Now I feel like we’ve delivered on the first promise. The next step is figuring out how big this gets.”

An interdisciplinary foundation

MIT’s prominent role in microbiome research came, in part, through its leadership in a field that may at first seem unrelated. For decades, MIT has made important contributions to microbial ecology, led by work in the Parsons Laboratory in the Department of Civil and Environmental Engineering and by scientists including Institute Professor Penny Chisholm.

Ecologists who use complex statistical techniques to study the relationships between organisms in different ecosystems are well-equipped to study the behavior of different bacterial strains in the microbiome.

Not that ecologists — or anyone else — initially had much to study involving the human microbiome, which was essentially a black box to researchers well into the 2000s. But the Human Genome Project led to faster, cheaper ways to sequence genes at scale, and a group of researchers including Alm and visiting professor Martin Polz began using those techniques to decode the genomes of environmental bacteria around 2008.

Those techniques were first pointed at the bacteria in the gut microbiome as part of the Human Microbiome Project, which began in 2007 and involved research groups from MIT and the Broad Institute.

Alm first got pulled into microbiome research by the late biological engineering professor David Schauer as part of a research project with Boston Children’s Hospital. It didn’t take much to get up to speed: Alm says the number of papers explicitly referencing the microbiome at the time could be read in an afternoon.

The collaboration, which included Ramnik Xavier, a core institute member of the Broad Institute, led to the first large-scale genome sequencing of the gut microbiome to diagnose inflammatory bowel disease. The research was funded, in part, by the Neil and Anna Rasmussen Family Foundation.

The study offered a glimpse into the microbiome’s diagnostic potential. It also underscored the need to bring together researchers from diverse fields to dig deeper.

Taking an interdisciplinary approach is important because, after next-generation sequencing techniques are applied to the microbiome, a large amount of computational biology and statistical methods are still needed to interpret the resulting data — the microbiome, after all, contains more genes than the human genome. One catalyst for early microbiome collaboration was the Microbiology Graduate PhD Program, which recruited microbiology students to MIT and introduced them to research groups across the Institute.

As microbiology collaborations increased among researchers from different department and labs, Neil Rasmussen, a longtime member of the MIT Corporation and a member of the visiting committees for a number of departments, realized there was still one more component needed to turn microbiome research into a force for human health.

“Neil had the idea to find all the clinical researchers in the [Boston] area studying diseases associated with the microbiome and pair them up with people like [biological engineers, mathematicians, and ecologists] at MIT who might not know anything about inflammatory bowel disease or microbiomes but had the expertise necessary to solve big problems in the field,” Alm says.

In 2014, that insight led the Rasmussen Foundation to support the creation of the Center for Microbiome Informatics and Therapeutics (CMIT), one of the first university-based microbiome research centers in the country.

Tami Lieberman, the Hermann L. F. von Helmholtz Career Development Professor at MIT, whose background is in ecology, says CMIT was a big reason she joined MIT’s faculty in 2018. Lieberman has developed new genomic approaches to study how bacteria mutate in healthy and sick individuals, with a particular focus on the skin microbiome.

Laura Kiessling, a chemist who has been recognized for contributions to our understanding of cell surface interactions, was also quick to joint CMIT. Kiessling, the Novartis Professor of Chemistry, has made discoveries relating to microbial mechanisms that influence immune function. Both Lieberman and Kiessling are also members of the Broad Institute.

Today, CMIT, co-directed by Alm and Xavier, facilitates collaborations between researchers and clinicians from hospitals around the country in addition to supporting research groups in the area. That work has led to hundreds of ongoing clinical trials that promise to further elucidate the microbiome’s connection to a broad range of diseases.

Fulfilling the promise of the microbiome

Researchers don’t yet know what specific strains of bacteria can improve the health of people with microbiome-associated diseases. But they do know that fecal matter transplants, which carry the full spectrum of gut bacteria from a healthy donor, can help patients suffering from certain diseases.

The nonprofit organization OpenBiome, founded by a group from MIT including Smith and Alm, launched in 2012 to help expand access to fecal matter transplants by screening donors for stool collection then processing, storing, and shipping samples to hospitals. Today OpenBiome works with more than 1,000 hospitals, and its success in the early days of the field shows that basic microbiome research, when paired with clinical trials like those happening at CMIT, can quickly lead to new treatments.

“You start with a disease, and if there’s a microbiome association, you can start a small trial to see if fecal transplants can help patients right away,” Alm explains. “If that becomes an effective treatment, while you’re rolling it out you can be doing the genomics to figure out how to make it better. So you can translate therapeutics into patients more quickly than when you’re developing small-molecule drugs.”

Another nonprofit project launched out of MIT, the Global Microbiome Conservancy, is collecting stool samples from people living nonindustrialized lifestyles around the world, whose guts have much different bacterial makeups and thus hold potential for advancing our understanding of host-microbiome interactions.

A number of private companies founded by MIT alumni are also trying to harness individual microbes to create new treatments, including, among others, Finch Therapeutics founded by Mark Smith; Concerto Biosciences, co-founded by Jared Kehe PhD ’20 and Bernardo Cervantes PhD ’20; BiomX, founded by Associate Professor Tim Lu; and Synlogic, founded by Lu and Jim Collins, the Termeer Professor of Medical Engineering and Science at MIT.

“There’s an opportunity to more precisely change a microbiome,” explains CMIT’s Lieberman. “But there’s a lot of basic science to do to figure out how to tweak the microbiome in a targeted way. Once we figure out how to do that, the therapeutic potential of the microbiome is quite limitless.”

Explained: Why RNA vaccines for Covid-19 raced to the front of the pack

Many years of research have enabled scientists to quickly synthesize RNA vaccines and deliver them inside cells.

Anne Trafton | MIT News Office
December 11, 2020

Developing and testing a new vaccine typically takes at least 12 to 18 months. However, just over 10 months after the genetic sequence of the SARS-CoV-2 virus was published, two pharmaceutical companies applied for FDA emergency use authorization of vaccines that appear to be highly effective against the virus.

Both vaccines are made from messenger RNA, the molecule that cells naturally use to carry DNA’s instructions to cells’ protein-building machinery. A vaccine based on mRNA has never been approved by the FDA before. However, many years of research have gone into RNA vaccines, which is one reason why scientists were able to start testing such vaccines against Covid-19 so quickly. Once the viral sequences were revealed in January, it took just days for pharmaceutical companies Moderna and Pfizer, along with its German partner BioNTech, to generate mRNA vaccine candidates.

“What’s particularly unique to mRNA is the ability to rapidly generate vaccines against new diseases. That I think is one of the most exciting stories behind this technology,” says Daniel Anderson, a professor of chemical engineering at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.

Most traditional vaccines consist of either killed or weakened forms of a virus or bacterium. These provoke an immune response that allows the body to fight off the actual pathogen later on.

Instead of delivering a virus or a viral protein, RNA vaccines deliver genetic information that allows the body’s own cells to produce a viral protein. Synthetic mRNA that encodes a viral protein can borrow this machinery to produce many copies of the protein. These proteins stimulate the immune system to mount a response, without posing any risk of infection.

A key advantage of mRNA is that it is very easy to synthesize once researchers know the sequence of the viral protein they want to target. Most vaccines for SARS-CoV-2 provoke an immune response that targets the coronavirus spike protein, which is found on the surface of the virus and gives the virus its characteristic spiky shape. Messenger RNA vaccines encode segments of the spike protein, and those mRNA sequences are much easier to generate in the lab than the spike protein itself.

“With traditional vaccines, you have to do a lot of development. You need a big factory to make the protein, or the virus, and it takes a long time to grow them,” says Robert Langer, the David H. Koch Institute Professor at MIT, a member of the Koch Institute, and one of the founders of Moderna. “The beauty of mRNA is that you don’t need that. If you inject nanoencapsulated mRNA into a person, it goes into the cells, and then the body is your factory. The body takes care of everything else from there.”

Langer has spent decades developing novel ways to deliver medicines, including therapeutic nucleic acids such as RNA and DNA. In the 1970s, he published the first study showing that it was possible to encapsulate nucleic acids, as well as other large molecules, in tiny particles and deliver them into the body. (Work by MIT Institute Professor Phillip Sharp and others on RNA splicing, which also laid groundwork for today’s mRNA vaccines, began in the ’70s as well.)

“It was very controversial at the time,” Langer recalls. “Everybody told us it was impossible, and my first nine grants were rejected. I spent about two years working on it, and I found over 200 ways to get it to not work. But then eventually I did find a way to get it to work.”

That paper, which appeared in Nature in 1976, showed that tiny particles made of synthetic polymers could safely carry and slowly release large molecules such as proteins and nucleic acids. Later, Langer and others showed that when polyethylene glycol (PEG) was added to the surface of nanoparticles, they could last in the body for much longer, instead of being destroyed almost immediately.

In subsequent years, Langer, Anderson, and others have developed fatty molecules called lipid nanoparticles that are also very effective at delivering nucleic acids. These carriers protect RNA from being broken down in the body and help to ferry it through cell membranes. Both the Moderna and Pfizer RNA vaccines are carried by lipid nanoparticles with PEG.

“Messenger RNA is a large hydrophilic molecule. It doesn’t naturally enter cells by itself, and so these vaccines are wrapped up in nanoparticles that facilitate their delivery inside of cells. This allows the RNA to be delivered inside of cells, and then translated into proteins,” Anderson says.

In 2018, the FDA approved the first lipid nanoparticle carrier for RNA, which was developed by Alnylam Pharmaceuticals to deliver a type of RNA called siRNA. Unlike mRNA, siRNA silences its target genes, which can benefit patients by turning off mutated genes that cause disease.

One drawback to mRNA vaccines is that they can break down at high temperatures, which is why the current vaccines are stored at such cold temperatures.  Pfizer’s SARS-CoV-2 vaccine has to be stored at -70 degrees Celsius (-94 degrees Fahrenheit), and the Moderna vaccine at -20 C (-4 F). One way to make RNA vaccines more stable, Anderson points out, is to add stabilizers and remove water from the vaccine through a process called lyophilization, which has been shown to allow some mRNA vaccines to be stored in a refrigerator instead of a freezer.

The striking effectiveness of both of these Covid-19 vaccines in phase 3 clinical trials (roughly 95 percent) offers hope that not only will those vaccines help to end the current pandemic, but also that in the future, RNA vaccines may help in the fight against other diseases such as HIV and cancer, Anderson says.

“People in the field, including myself, saw a lot of promise in the technology, but you don’t really know until you get human data. So to see that level of protection, not just with the Pfizer vaccine but also with Moderna, really validates the potential of the technology — not only for Covid, but also for all these other diseases that people are working on,” he says. “I think it’s an important moment for the field.”

3 Questions: Phillip Sharp on the discoveries that enabled RNA vaccines for Covid-19

Curiosity-driven basic science in the 1970s laid the groundwork for today’s leading vaccines against the novel coronavirus.

School of Science
December 11, 2020

Some of the most promising vaccines developed to combat Covid-19 rely on messenger RNA (mRNA) — a template cells use to carry genetic instructions for producing proteins. The mRNA vaccines take advantage of this cellular process to make proteins that then trigger an immune response that targets SARS-CoV-2, the virus that causes Covid-19.

Compared to other types of vaccines, recently developed technologies allow mRNA vaccines to be rapidly created and deployed on a large-scale — crucial aspects in the fight against Covid-19. Within the year since the identification and sequencing of the SARS-CoV-2 virus, companies such as Pfizer and Moderna have developed mRNA vaccines and run large-scale trials in the race to have a vaccine approved by the U.S. Food and Drug Administration — a feat unheard of with traditional vaccines using live attenuated or inactive viruses. These vaccines appear to have a greater than 90 percent efficacy in protecting against infection.

The fact that these vaccines could be rapidly developed within these last 10 months rests on more than four decades of study of mRNA. This success story begins with Institute Professor Phillip A. Sharp’s discovery of split genes and spliced RNA that took place at MIT in the 1970s — a discovery that would earn him the 1993 Nobel Prize in Physiology or Medicine.

Sharp, a professor within the Department of Biology and member of the Koch Institute for Integrative Cancer Research at MIT, commented on the long arc of scientific research that has led to this groundbreaking, rapid vaccine development — and looked ahead to what the future might hold for mRNA technology.

Q: Professor Sharp, take us back to the fifth floor of the MIT Center for Cancer Research in the 1970s. Were you and your colleagues thinking about vaccines when you studied viruses that caused cancer?

A: Not RNA vaccines! There was a hope in the ’70s that viruses were the cause of many cancers and could possibly be treated by conventional vaccination with inactivated virus. This is not the case, except for a few cancers such as HPV causing cervical cancer.

Also, not all groups at the MIT Center for Cancer Research (CCR) focused directly on cancer. We knew so little about the causes of cancer that Professor Salvador Luria, director of the CCR, recruited faculty to study cells and cancer at the most fundamental level. The center’s three focuses were virus and genetics, cell biology, and immunology. These were great choices.

Our research was initially funded by the American Cancer Society, and we later received federal funding from the National Cancer Institute, part of the National Institutes of Health and the National Science Foundation — as well as support from MIT through the CCR, of course.

At Cold Spring Harbor Laboratory in collaboration with colleagues, we had mapped the parts of the adenovirus genome responsible for tumor development. While doing so, I became intrigued by the report that adenovirus RNA in the nucleus was longer than the RNA found outside the nucleus in the cytoplasm where the messenger RNA was being translated into proteins. Other scientists had also described longer-than-expected nuclear RNA from cellular genes, and this seemed to be a fundamental puzzle to solve.

Susan Berget, a postdoc in my lab, and Claire Moore, a technician who ran MIT’s electron microscopy facility for the cancer center and would later be a postdoc in my lab, were instrumental in designing the experiments that would lead to the iconic electron micrograph that was the key to unlocking the mystery of this “heterogeneous” nuclear RNA. Since those days, Sue and Claire have had successful careers as professors at Baylor College of Medicine and Tufts Medical School, respectively.

The micrograph showed loops that would later be called “introns” — unnecessary extra material in between the relevant segments of mRNA, or “exons.” These exons would be joined together, or spliced, to create the final, shorter message for the translation to proteins in the cytoplasm of the cell.

This data was first presented at the Cancer Center fifth floor group meeting that included Bob Weinberg, David Baltimore, David Housman, and Nancy Hopkins. Their comments, particularly those of David Baltimore, were catalysts in our discovery. Our curiosity to understand this basic cellular mechanism drove us to learn more, to design the experiments that could elucidate the RNA splicing process. The collaborative environment of the MIT Cancer Center allowed us to share ideas and push each other to see problems in a new way.

Q: Your discovery of RNA splicing was a turning point, opening up new avenues that led to new applications. What did this foundation allow you to do that you couldn’t do before?

A: Our discovery in 1977 occurred just as biotechnology appeared with the objective of introducing complex human proteins as therapeutic agents, for example interferons and antibodies. Engineering genes to express these proteins in industrial tanks was dependent on this discovery of gene structure. The same is true of the RNA vaccines for Covid-19: By harnessing new technology for synthesis of RNA, researchers have developed vaccines whose chemical structure mimics that of cytoplasmic mRNA.

In the early 1980s, following isolation of many human mutant disease genes, we recognized that about one-fifth of these were defective for accurate RNA splicing. Further, we also found that different isoforms of mRNAs encoding different proteins can be generated from a single gene. This is “alternative RNA splicing” and may explain the puzzle that humans have fewer genes — 21,000 to 23,000 — than many less complex organisms, but these genes are expressed in more complex protein isoforms. This is just speculation, but there are so many things about biology yet to be discovered.

I liken RNA splicing to discovering the Rosetta Stone. We understood how the same letters of the alphabet could be written and rewritten to form new words, new meaning, and new languages. The new “language” of mRNA vaccines can be developed in a laboratory using a DNA template and readily available materials. Knowing the genetic code of the SARS-CoV-2 is the first step in generating the mRNA vaccine. The effective delivery of vaccines into the body based on our fundamental understanding of mRNA took decades more work and ingenuity to figure out how to evade other cellular mechanisms perfected over hundreds of millions of years of evolution to destroy foreign genetic material.

Q: Looking ahead 40 more years, where do you think mRNA technology might be?

A: In the future, mRNA vaccine technology may allow for one vaccine to target multiple diseases. We could also create personalized vaccines based on individuals’ genomes.

Messenger RNA vaccines have several benefits compared to other types of vaccines, including the use of noninfectious elements and shorter manufacturing times. The process can scaled up, making vaccine development faster than traditional methods. RNA vaccines can also be moved rapidly into clinical trials, which is critical for the next pandemic.

It is impossible to predict the future of RNA therapies, such as the new vaccines, but there are some signs that new advancements could happen very quickly. A few years ago, the first RNA-based therapy was approved for treatment of lethal genetic disease. This treatment was designed through the discovery of RNA interference. Messenger RNA-based therapies will also likely be used to treat genetic diseases, vaccinate against cancer, and generate transplantable organs. It is another tool at the forefront of modern medical care.

But keep in mind that all mRNAs in human cells are encoded by only 2 percent of the total genome sequence. Most of the other 98 percent is transcribed into cellular RNAs whose activities remain to be discovered. There could be many future RNA-based therapies.

MIT labs win top recognition for sustainable practices in cold storage management

Whitehead Institute and MIT named 2020 Organizational Winners in the fourth annual International Institute for Sustainable Laboratories International Laboratory Freezer Challenge.

Environment, Health and Safety Office
December 9, 2020

In its fourth year, the International Institute for Sustainable Laboratories (I2SL) International Laboratory Freezer Challenge drew 218 laboratory participants from around the world, from 88 research institutions. Three MIT laboratories participated in the challenge: the Department of Biology’s Barbara Imperiali Lab, Department of Biological Engineering’s Jacquin Niles Lab, and Department of Biology/Whitehead Institute for Biomedical Research’s David Sabatini Lab. MIT and the Whitehead Institute together received the Top Academic Organization Award. The Niles lab and the Imperiali lab are MIT Environment, Health & Safety (EHS) Green Lab Certified.

The Freezer Challenge, which is run by the nonprofit organizations My Green Labs and I2SL, is aimed at promoting efficient, effective sample storage for laboratories around the world, and using a spirit of friendly competition to increase sample accessibility, sample integrity, reduced costs, and energy efficiency.

Over a five-month period, challenge contestants implement optimal cold storage management practices, such as defrosting and removing dust from freezer intake or coils, regular cleanouts, organization of inventory on file, and high-density storage. Winners are then chosen based on the amount of energy saved. Additionally, in the spirit of friendly competition and collaboration that pervades the challenge, contestants can earn points for sharing tips about their own cold storage best practices.

This year, the 218 laboratory participants saved an estimated total of 3.2 million kilowatt-hours (kWh) per year, up from 2.4 million in 2019. The savings represents the equivalent of reducing carbon emissions by 2,260 metric tons per year, or removing 360 passenger vehicles from the road for a year. According to Christina Greever, operations manager at My Green Labs, the three participating MIT and Whitehead Institute labs saved an estimated 520 kWh/year.

Two of the three labs — Niles and Imperiali — have previously participated in MIT EHS’ Green Labs Freezer Challenge, and have consequently instituted good management practices surrounding cold storage. The Sabatini lab hasn’t previously participated in EHS’ challenge, but had also already implemented many of the practices the challenge encourages and rewards.

Edith Valeri, of the Sabatini lab, said that while her lab didn’t face any major difficulties, the challenge encouraged lab management staff to be “more aware of freezer usage” and “more mindful of wattage usage, turning down temperatures to a sustainable level, and defrosting the freezers.”

Similarly, both Sebastian Smick, a technical associate in the Niles lab, and Christine Arbour, an NIH postdoc in the Imperiali lab, found that participating in the challenge was not disruptive to operations, and the only difficulties they ran into came as a result of the Covid response. Because of their previous participation in  the MIT EHS’ Green Labs Freezer Challenge, efficient energy usage is already routine for the three labs.

Smick described the challenge as “a good incentive” for the Niles lab to practice regular thawing, and “a nice way to quantify what it means to the University’s power consumption.” He credits MIT Custodial Services for the invaluable support they provide on a regular basis. “Custodial Services is always there for us during our thaws to provide mopping and absorbent barriers while we thaw. Most of the ice is captured as a solid, but spillover is unavoidable. They’ve saved us thousands of paper towels!”

The Imperiali lab upgraded its cold storage in March, replacing its minus-80 degrees Celsius freezer with a newer, more energy efficient model, and entered the challenge ready to focus on maximizing that investment. “Our lab consistently cleans our freezer filters, -80 degree C freezer in particular, to prevent the compressor from overworking,” says Arbour. “We are also vigilant with appropriate chemical storage. We store chemicals at the temperature that the supplier/company recommends and nothing colder. This prevents overcrowding in –20 and –80 degree C freezers, which can start to add up!”

For Smick, a key takeaway from the challenge was the quantification of the power consumption of his lab’s cold storage. “I was so surprised when I first learned about the power consumption of our -80 C and -20 freezers,” he recalls. “It’s easy to see the impact of changing to a cheaper reagent or eliminating a wasteful process when it is something that comes directly out of your pocket, but electricity is something we take for granted; it should be conserved like any natural resource, and this challenge really shines an environmentally friendly, zero-energy consumption light on how easy it is to make a huge impact.”

Smick credits the challenge with inspiring his lab to conduct regular thaws, a major energy-saving practice. “I know for a fact that, prior to our regular freezer thaws which we started doing because of this competition, we were throwing away thousands of dollars of reagents away each year because they were lost in the glaciers that we were maintaining in our freezers.”

Similarly, Arbour says the Imperiali lab will continue to implement the practices recognized in the challenge. “Our lab practices will continue to evolve with new green practices,” she says. “Our entire lab is invested in doing better for the environment.”

“My hope is that competitions like this inspire MIT and the entire world to take a more serious look about how we deal with the resources available to us: from electricity to recyclable waste,” says Smick. “Science generates a huge amount of waste, and there is so much more that we can do to reduce environmental impact, and to offset the cost of generating meaningful data.”

MIT EHS has plans in the works for the enhancement and expansion of the Institute’s Green Labs program, and will be implementing them in the upcoming year. Labs interested in learning more about the Green Labs program, its benefits, and details on how to participate should contact environment@mit.edu.

Six MIT faculty elected 2020 AAAS Fellows

Choucri, Drennan, Fisher, Gershenfeld, Li, and Rus are recognized for their efforts to advance science.

MIT News Office
November 24, 2020

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

The new fellows are among a group of 489 AAAS members elected by their peers in recognition of their scientifically or socially distinguished efforts to advance science.

A virtual induction ceremony for the new fellows will be held on Feb. 13, 2021. 

Nazli Choucri is a professor of political science, a senior faculty member at the Center of International Studies (CIS), and a faculty affiliate at the Institute for Data, Science, and Society (IDSS). She works in the areas of international relations, conflict and violence, and the international political economy, with a focus on cyberspace and the global environment. Her current research is on cyberpolitics in international relations, focusing on linking integrating cyberspace into the fabric of international relations.

Catherine Drennan is a professor in the departments of Biology and Chemistry. Her research group seeks to understand how nature harnesses and redirects the reactivity of enzyme metallocenters in order to perform challenging reactions. By combining X-ray crystallography with other biophysical methods, the researchers’ goal is to “visualize” molecular processes by obtaining snapshots of enzymes in action.

Peter Fisher is a professor in the Department of Physics and currently serves as department head. He carries out research in particle physics in the areas of dark matter detection and the development of new kinds of particle detectors. He is also interested in compact energy supplies and wireless energy transmission.

Neil Gershenfeld is the director of MIT’s Center for Bits and Atoms, which works to break down boundaries between the digital and physical worlds, from pioneering quantum computing to digital fabrication to the “internet of things.” He is the founder of a global network of over 1,000 fab labs, chairs the Fab Foundation, and leads the Fab Academy.

Ju Li is the Battelle Energy Alliance Professor of Nuclear Science and Engineering and a professor of materials science and engineering. He studies how atoms and electrons behave and interact, to inform the design new materials from the atomic level on up. His research areas include overcoming timescale challenges in atomistic simulations, energy storage and conversion, and materials in extreme environments and far from equilibrium.

Daniela Rus is the Andrew and Erna Viterbi Professor of Electrical Engineering and Computer Science and director of the Computer Science and Artificial Intelligence Laboratory (CSAIL) at MIT. Her research interests include robotics, mobile computing, and data science. Rus is a Class of 2002 MacArthur Fellow, a fellow of ACM, AAAI and IEEE, and a member of the National Academy of Engineering, and the American Academy for Arts and Science.

This year’s fellows will be formally announced in the AAAS News and Notes section of Science on Nov. 27.

Aspiring physician explores the many levels of human health

During her time at MIT, senior Ayesha Ng’s interests have expanded from cellular biology to the social systems that shape public health.

Alison Gold | School of Science
November 9, 2020

It was her childhood peanut allergy that first sparked senior Ayesha Ng’s fascination with the human body. “To see this severe reaction happen to my body and not know what was happening — that made me a lot more curious about biology and living systems,” Ng says.

She didn’t exactly plan it this way. But in her three and a half years at MIT, Ng, a biology and cognitive and brain sciences double major from the Los Angeles, California area, has conducted research and taken classes examining just about every level of human health — from cellular to societal.

Most recently, her passion for medicine and health equity led her to the National Foundation for the Centers for Disease Control and Prevention (CDC), where, this summer, she worked to develop guidelines for addressing health disparities on state and local health jurisdictions’ Covid-19 data dashboards. Now, as an aspiring physician amidst the medical school application process, Ng has a sense of how microbiological, physiological, and social systems interact to affect a person’s health.

Starting small

Throughout her entire first year at MIT, Ng studied the biology of health at a cellular level. Specifically, she researched the effects of fasting and aging on regeneration of intestinal stem cells, which are located in the human intestinal crypts and continuously self-divide and reproduce. Understanding these metabolic mechanisms is crucial, as their deregulation can lead to age-associated diseases such as cancer.

“That experience allowed me to broaden my technical skills, just getting used to so many different types of molecular biological techniques right away, which I really appreciated,” Ng says of her time at the Whitehead Institute for Biomedical Research in Professor David Sabatini’s lab.

“After some time, I realized that I also wanted to also study sciences at a broader, more macro level, instead of only the microbiology and molecular biology that we were studying in Course 7,” Ng says of her biology major.

In addition to studying the biology of cancer, Ng had developed a curiosity about the human brain and how it functions. “I was really interested in that, because my grandpa has dementia,” Ng says.

Seeing her grandfather’s cognitive decline, she was inspired to become involved in MIT BrainTrust, a student organization that offers a social support network for individuals from around the Boston, Massachusetts area who have brain injuries. “We have these meetings, in which I serve as one of only one or two students there to facilitate a safe space where we can have all these individuals with brain injury gather,” Ng says of the peer-support aspect of the program. “They can really share their mutual challenges and experiences.”

Investigating the brain

To pursue her interest in brain research and the societal impact of brain injuries, Ng traveled to the University of Hong Kong the summer after her first year as an MIT International Science and Technology Initiatives (MISTI) China Fung Scholar. Working with Professor Raymond Chang, she began to examine neurodegenerative disease and used tissue-clearing techniques to visualize 3D mouse brain structures at cellular resolution. “That was personally meaningful for me, to research about that and learn more about dementia,” Ng says.

Returning to MIT her sophomore year, Ng was certain that she wanted to continue studying the brain. She began working on Alzheimer’s research at the MIT Picower Institute for Learning and Memory in the lab of Professor Li-Huei Tsai, the Picower Professor of Neuroscience at MIT. Much existing research into Alzheimer’s disease has been at the bulk-tissue level, focusing on the neurons’ role in neurodegeneration associated with aging.

Ng’s work with Tsai considers the complexity of alterations across genes and less-abundant cell types, such as microglia, astrocytes, and other supporting glial cells that become dysregulated in the brains of patients with Alzheimer’s. Considering the interplay between and within cell types during neurodegeneration is most intriguing to her. While some molecular processes are protective, other damaging ones simultaneously occur and can exist even within the same cell type. This intricacy has made the mechanistic basis behind Alzheimer’s progression elusive and the research that much more crucial.

“It’s really interesting to see how heterogeneous and complex the responses are in Alzheimer’s brains,” Ng says of the research program with Tsai, a founding director of MIT’s Aging Brain Initiative. “I really think about these potential new drug targets to improve treatment for Alzheimer’s in the future because I have seen, with my grandpa especially, how treatment is really lacking in the neurodegeneration field. There’s no treatment that’s been able to stop or even slow the progression of Alzheimer’s disease.”

Her research project in the Tsai Lab relies on a technology called single-nucleus RNA sequencing (snRNA-seq), which extracts the genomic information contained in individual cells. This is followed by computational dimension reduction and clustering algorithms to examine how Alzheimer’s disease differentially affects genes and specific cell types.

“With that project, we’ve been able to use single-nucleus RNA sequencing to really look at the brains of human Alzheimer’s patients,” Ng says. “And with the single-cell technology, we’re able to look at brain tissue at a much higher resolution, allowing us to see that there’s so much heterogeneity within the brain.”

After conducting more than a year of Alzheimer’s research and then taking a human physiology class in her third year, Ng decided to add a second major in brain and cognitive sciences to gain deeper insight specifically into how the nervous system within the body functions.

“That class really allowed me to realize that I really love organ systems and wanted to study by looking at more physiological mechanisms,” Ng says. “It has been really great to, at the end of my college career, really delve more into a very specific system.”

Medicine and society

Having gained perspective on cellular and microbiology, and human organ systems, Ng decided to zoom out further, interning this past summer at the National Foundation for the CDC. She found the opportunity through MIT’s PKG Center, applied as one of 60 candidates, and was selected for a team of four. There, as a member of the CDC Foundation’s Health Equity Strike Team, she examined how to increase transparency of publicly available Covid-19 data on health disparities and how the narrative tied to health equity can be modified in public health messages. This involved harnessing data about the demographics of those most affected during Covid-19 — including how infection and mortality rates differ starkly based on social factors including housing conditions, socioeconomic status, race, and ethnicity.

“Thinking about all these factors, we compiled a set of best practices for how to present data about Covid-19, what data should be collected, and tried to push those out to help jurisdictions as best-practice recommendations,” Ng says. “That did really increase my interest in health equity and made me realize how important public health is as well.”

Amidst the Covid-19 pandemic, Ng is spending the first semester of her senior year at home with her family in the Los Angeles area. “I really miss the people and not being able to interact with not only other students and peers, but also faculty as well,” she says. “I really wanted to enjoy time with friends, and just explore more of MIT, too, which I didn’t always get the chance to do over the past few years.”

Still, she continues to participate in both BrainTrust and MIT’s Asian Dance team, remotely, through weekly practices on Zoom.

“I think dance is one of the biggest de-stressors for me; I had never done dance before going to college. Getting to meet this team and join this community allowed me not only to connect to my Asian cultural roots, but also just expose myself to this new art form where I could really learn how to express myself on stage,” Ng says. “And that really has been the source of relief for me to just liberate any worries that I have, and has increased my sense of self-awareness and self-confidence.”

Armed with the many experiences she has enjoyed at MIT, both in and out of the classroom, Ng plans to continue studying both medicine and public health. She’s excited to explore different potential specialties and is currently most intrigued by surgery. Whichever specialty she may choose, she is determined to include health equity and cultural sensitivity in her practice.

“Seeing surgeons, I personally think that being able to physically heal a patient with my own hands, that would be the most rewarding feeling,” Ng says. “I will strive to, as a physician, use whatever platform that I have to advocate for patients and really drive health-care systems to overcome disparities.”

Angelika Amon, cell biologist who pioneered research on chromosome imbalance, dies at 53

Professor and mentor for more than 20 years at MIT redefined scientists’ understanding of the biology of cell division and proliferation.

Bendta Schroeder | Koch Institute
October 30, 2020

Angelika Amon, professor of biology and a member of the Koch Institute for Integrative Cancer Research, died on Oct. 29 at age 53, following a two-and-a-half-year battle with ovarian cancer.

“Known for her piercing scientific insight and infectious enthusiasm for the deepest questions of science, Professor Amon built an extraordinary career – and in the process, a devoted community of colleagues, students and friends,” MIT President L. Rafael Reif wrote in a letter to the MIT community.

“Angelika was a force of nature and a highly valued member of our community,” reflects Tyler Jacks, the David H. Koch Professor of Biology at MIT and director of the Koch Institute. “Her intellect and wit were equally sharp, and she brought unmatched passion to everything she did. Through her groundbreaking research, her mentorship of so many, her teaching, and a host of other contributions, Angelika has made an incredible impact on the world — one that will last long into the future.”

A pioneer in cell biology

From the earliest stages of her career, Amon made profound contributions to our understanding of the fundamental biology of the cell, deciphering the regulatory networks that govern cell division and proliferation in yeast, mice, and mammalian organoids, and shedding light on the causes of chromosome mis-segregation and its consequences for human diseases.

Human cells have 23 pairs of chromosomes, but as they divide they can make errors that lead to too many or too few chromosomes, resulting in aneuploidy. Amon’s meticulous and rigorous experiments, first in yeast and then in mammalian cells, helped to uncover the biological consequences of having too many chromosomes. Her studies determined that extra chromosomes significantly impact the composition of the cell, causing stress in important processes such as protein folding and metabolism, and leading to additional mistakes that could drive cancer. Although stress resulting from aneuploidy affects cells’ ability to survive and proliferate, cancer cells — which are nearly universally aneuploid — can grow uncontrollably. Amon showed that aneuploidy disrupts cells’ usual error-repair systems, allowing genetic mutations to quickly accumulate.

Aneuploidy is usually fatal, but in some instances extra copies of specific chromosomes can lead to conditions such as Down syndrome and developmental disorders including those known as Patau and Edwards syndromes. This led Amon to work to understand how these negative effects result in some of the health problems associated specifically with Down syndrome, such as acute lymphoblastic leukemia. Her expertise in this area led her to be named co-director of the recently established Alana Down Syndrome Center at MIT.

“Angelika’s intellect and research were as astonishing as her bravery and her spirit. Her lab’s fundamental work on aneuploidy was integral to our establishment of the center,” say Li-Huei Tsai, the Picower Professor of Neuroscience and co-director of the Alana Down Syndrome Center. “Her exploration of the myriad consequences of aneuploidy for human health was vitally important and will continue to guide scientific and medical research.”

Another major focus of research in the Amon lab has been on the relationship between how cells grow, divide, and age. Among other insights, this work has revealed that once cells reach a certain large size, they lose the ability to proliferate and are unable to reenter the cell cycle. Further, this growth contributes to senescence, an irreversible cell cycle arrest, and tissue aging. In related work, Amon has investigated the relationships between stem cell size, stem cell function, and tissue age. Her lab’s studies have found that in hematopoetic stem cells, small size is important to cells’ ability to function and proliferate — in fact, she posted recent findings on bioRxiv earlier this week — and have been examining the same questions in epithelial cells as well.

Amon lab experiments delved deep into the mechanics of the biology, trying to understand the mechanisms behind their observations. To support this work, she established research collaborations to leverage approaches and technologies developed by her colleagues at the Koch Institute, including sophisticated intestinal organoid and mouse models developed by the Yilmaz Laboratory, and a microfluidic device developed by the Manalis Laboratory for measuring physical characteristics of single cells.

The thrill of discovery

Born in 1967, Amon grew up in Vienna, Austria, in a family of five. Playing outside all day with her three younger siblings, she developed an early love of biology and animals. She could not remember a time when she was not interested in biology, initially wanting to become a zoologist. But in high school, she saw an old black-and-white film from the 1950s about chromosome segregation, and found the moment that the sister chromatids split apart breathtaking. She knew then that she wanted to study the inner workings of the cell and decided to focus on genetics at the University of Vienna in Austria.

After receiving her BS, Amon continued her doctoral work there under Professor Kim Nasmyth at the Research Institute of Molecular Pathology, earning her PhD in 1993. From the outset, she made important contributions to the field of cell cycle dynamics. Her work on yeast genetics in the Nasmyth laboratory led to major discoveries about how one stage of the cell cycle sets up for the next, revealing that cyclins, proteins that accumulate within cells as they enter mitosis, must be broken down before cells pass from mitosis to G1, a period of cell growth.

Towards the end of her doctorate, Amon became interested in fruitfly genetics and read the work of Ruth Lehmann, then a faculty member at MIT and a member of the Whitehead Institute. Impressed by the elegance of Lehmann’s genetic approach, she applied and was accepted to her lab. In 1994, Amon arrived in the United States, not knowing that it would become her permanent home or that she would eventually become a professor.

While Amon’s love affair with  fruitfly genetics would prove short, her promise was immediately apparent to Lehmann, now director of the Whitehead Institute. “I will never forget picking Angelika up from the airport when she was flying in from Vienna to join my lab. Despite the long trip, she was just so full of energy, ready to talk science,” says Lehmann. “She had read all the papers in the new field and cut through the results to hit equally on the main points.”

But as Amon frequently was fond of saying, “yeast will spoil you.” Lehmann explains that “because they grow so fast and there are so many tools, ‘your brain is the only limitation.’ I tried to convince her of the beauty and advantages of my slower-growing favorite organism. But in the end, yeast won and Angelika went on to establish a remarkable body of work, starting with her many contributions to how cells divide and more recently to discover a cellular aneuploidy program.”

In 1996, after Lehmann had left for New York University’s Skirball Institute, Amon was invited to become a Whitehead Fellow, a prestigious program that offers recent PhDs resources and mentorship to undertake their own investigations. Her work on the question of how yeast cells progress through the cell cycle and partition their chromosomes would be instrumental in establishing her as one of the world’s leading geneticists. While at Whitehead, her lab made key findings centered around the role of an enzyme called Cdc14 in prompting cells to exit mitosis, including that the enzyme is sequestered in a cellular compartment called the nucleolus and must be released before the cell can exit.

“I was one of those blessed to share with her a ‘eureka moment,’ as she would call it,” says Rosella Visintin, a postdoc in Amon’s lab at the time of the discovery and now an assistant professor at the European School of Molecular Medicine in Milan. “She had so many. Most of us are lucky to get just one, and I was one of the lucky ones. I’ll never forget her smile and scream — neither will the entire Whitehead Institute — when she saw for the first time Cdc14 localization: ‘You did it, you did it, you figured it out!’ Passion, excitement, joy — everything was in that scream.”

In 1999, Amon’s work as a Whitehead Fellow earned her a faculty position in the MIT Department of Biology and the MIT Center for Cancer Research, the predecessor to the Koch Institute. A full professor since 2007, she also became the Kathleen and Curtis Marble Professor in Cancer Research, associate director of the Paul F. Glenn Center for Biology of Aging Research at MIT, a member of the Ludwig Center for Molecular Oncology at MIT, and an investigator of the Howard Hughes Medical Institute.

Her pathbreaking research was recognized by several awards and honors, including the 2003 National Science Foundation Alan T. Waterman Award, the 2007 Paul Marks Prize for Cancer Research, the 2008 National Academy of Sciences (NAS) Award in Molecular Biology, and the 2013 Ernst Jung Prize for Medicine. In 2019, she won the Breakthrough Prize in Life Sciences and the Vilcek Prize in Biomedical Science, and was named to the Carnegie Corporation of New York’s annual list of Great Immigrants, Great Americans. This year, she was given the Human Frontier Science Program Nakasone Award. She was also a member of the NAS and the American Academy of Arts and Sciences.

Lighting the way forward

Amon’s perseverance, deep curiosity, and enthusiasm for discovery served her well in her roles as teacher, mentor, and colleague. She has worked with many labs across the world and developed a deep network of scientific collaboration and friendships. She was a sought-after speaker for seminars and the many conferences she attended. In over 20 years as a professor at MIT, she has mentored more than 80 postdocs, graduate students, and undergraduates, and received the School of Science’s undergraduate teaching prize.

“Angelika was an amazing, energetic, passionate, and creative scientist, an outstanding mentor to many, and an excellent teacher,” says Alan Grossman, the Praecis Professor of Biology and head of MIT’s Department of Biology. “Her impact and legacy will live on and be perpetuated by all those she touched.”

“Angelika existed in a league of her own,” explains Kristin Knouse, one of Amon’s former graduate students and a current Whitehead Fellow. “She had the energy and excitement of someone who picked up a pipette for the first time, but the brilliance and wisdom of someone who had been doing it for decades. Her infectious energy and brilliant mind were matched by a boundless heart and tenacious grit. She could glance at any data and immediately deliver a sharp insight that would never have crossed any other mind. Her positive attributes were infectious, and any interaction with her, no matter how transient, assuredly left you feeling better about yourself and your science.”

Taking great delight in helping young scientists find their own “eureka moments,” Amon was a fearless advocate for science and the rights of women and minorities and inspired others to fight as well. She was not afraid to speak out in support of the research and causes she believed strongly in. She was a role model for young female scientists and spent countless hours mentoring and guiding them in a male-dominated field. While she graciously accepted awards for women in science, including the Vanderbilt Prize and the Women in Cell Biology Senior Award, she questioned the value of prizes focused on women as women, rather than on their scientific contributions.

“Angelika Amon was an inspiring leader,” notes Lehmann, “not only by her trailblazing science but also by her fearlessness to call out sexism and other -isms in our community. Her captivating laugh and unwavering mentorship and guidance will be missed by students and faculty alike. MIT and the science community have lost an exemplary leader, mentor, friend, and mensch.”

Amon’s wide-ranging curiosity led her to consider new ideas beyond her own field. In recent years, she has developed a love for dinosaurs and fossils, and often mentioned that she would like to study terraforming, which she considered essential for a human success to life on other planets.

“It was always amazing to talk with Angelika about science, because her interests were so deep and so broad, her intellect so sharp, and her enthusiasm so infectious,” remembers Vivian Siegel, a lecturer in the Department of Biology and friend since Amon’s postdoctoral days. “Beyond her own work in the lab, she was fascinated by so many things, including dinosaurs — dreaming of taking her daughters on a dig — lichen, and even life on Mars.”

“Angelika was brilliant; she illuminated science and scientists,” says Frank Solomon, professor of biology and member of the Koch Institute. “And she was intense; she warmed the people around her, and expanded what it means to be a friend.”

Amon is survived by her husband Johannes Weis, and her daughters Theresa and Clara Weis, and her three siblings and their families.

Tyler Jacks, founding director of MIT’s Koch Institute, to step down

A search committee chaired by Institute Professor Phillip Sharp will work to identify a new director for the MIT’s pioneering cancer research center.

Bendta Schroeder | Koch Institute
October 26, 2020

The Koch Institute for Integrative Cancer Research at MIT, a National Cancer Institute (NCI)-designated cancer center, has announced that Tyler Jacks will step down from his role as director, pending selection of his successor.

“An exceptionally creative scientist and a leader of great vision, Tyler also has a rare gift for launching and managing large, complex organizations, attracting exceptional talent and inspiring philanthropic support,” says MIT President L. Rafael Reif. “We are profoundly grateful for all the ways he has served MIT, including most recently his leadership on the Research Ramp Up Lightning Committee, which made it possible for MIT’s research enterprise to resume in safe ways after the initial Covid shutdown. I offer warmest admiration and best wishes as Tyler steps down from leading the Koch and returns full time to the excitement of the lab.”

Jacks, the David H. Koch Professor of Biology, has served as director for more than 19 years, first for the MIT Center for Cancer Research (CCR) and then for its successor, the Koch Institute. The CCR was founded by Nobel laureate Salvador Luria in 1974, shortly after the federal government declared “war on cancer,” with the mission of unravelling the molecular core of cancer. Jacks became the center’s fourth director in 2001, following Luria, Nobel laureate and Institute Professor Phillip Sharp, and Daniel K. Ludwig Professor for Cancer Research Richard Hynes.

Aided by the championship of then-MIT President Susan Hockfield and a gift of $100 million from MIT alumnus David H. Koch ’62, SM ’63, Jacks oversaw the evolution of the Center for Cancer Research into the Koch Institute in 2007 as well as the construction of a new home in Building 76, completed in 2010. The Koch Institute expands the mission of its predecessor by bringing life scientists and engineers together to advance understanding of the basic biology of cancer, and to develop new tools to better diagnose, monitor, and treat the disease.

Under the direction of Jacks, the institute has become an engine of collaborative cancer research at MIT. “Tyler’s vision and execution of a convergent cancer research program has propelled the Koch Institute to the forefront of discovery,” notes Maria Zuber, MIT’s vice president for research.

Bolstered by the Koch Institute’s associate directors Jacqueline Lees, Matthew Vander Heiden, Darrell Irvine, and Dane Wittrup, Jacks oversaw four successful renewals of the coveted NCI-designated cancer center stature, with the last two renewals garnering perfect scores. In 2015, Jacks was the recipient of the James R. Killian Jr. Faculty Achievement Award, the highest honor the MIT faculty can bestow upon one of its members, for his leadership in cancer research and for his role in establishing the Koch Institute.

“Tyler Jacks turned the compelling idea to accelerate progress against cancer by bringing together fundamental biology, engineering know-how, and clinical expertise, into the intensively collaborative environment that is now the Koch Institute for Integrative Cancer Research,” says Hockfield. “His extraordinary leadership has amplified the original idea into a paradigm-changing approach to cancer, which now serves as a model for research centers around the world.”

To support cross-disciplinary research in high-impact areas and expedite translation from the bench to the clinic, Jacks and his colleagues shepherded the creation of numerous centers and programs, among them the Ludwig Center for Molecular Oncology, the Marble Center for Cancer Nanomedicine, the MIT Center for Precision Cancer Medicine, the Swanson Biotechnology Center, the Lustgarten Lab for Pancreatic Cancer Research, and the MIT Stem Cell Initiative. In addition, Jacks has co-led the Bridge Project, a collaboration between the Koch Institute and Dana-Farber/Harvard Cancer Center that brings bioengineers, cancer scientists, and clinical oncologists together to solve some of the most challenging problems in cancer research. Jacks has raised nearly $375 million in support of these efforts, as well as the building of the Koch Institute facility, the Koch Institute Frontier Research Program, and other activities.

Jacks first became interested in cancer as a Harvard University undergraduate while attending a lecture by Robert Weinberg, the Daniel K. Ludwig Professor of Cancer Research and member of the Whitehead Institute, who is himself a pioneer in cancer genetics. After earning his PhD at the University of California at San Francisco under the direction of Nobel laureate Harold Varmus, Jacks joined Weinberg’s lab as a postdoctoral fellow. He joined the MIT faculty in 1992 with appointments in the Center for Cancer Research and the Department of Biology.

Jacks is widely considered a leader in the development of engineered mouse models of human cancers, and has pioneered the use of gene-targeting technology to construct mouse models and to study cancer-associated genes in mice. Strains of mice developed in his lab are used by researchers around the world, as well as by neighboring labs within the Koch Institute. Because these models closely resemble human forms of the disease, they have allowed researchers to track how tumors progress and to test new ways to detect and treat cancer. In more recent research, Jacks has been using mouse models to investigate how immune and tumor cells interact during cancer development and how tumors successfully evade immune recognition. This research is expected to lead to new immune-based therapies for human cancer.

Outside his research and MIT leadership, Jacks co-chaired the Blue Ribbon Panel for the National Cancer Moonshot Initiative, chaired the National Cancer Advisory Board of the National Cancer Institute, and is a past president of the American Association for Cancer Research. He is an elected member of the National Academy of Science, the National Academy of Medicine and the American Academy of Arts and Sciences. Jacks serves on the Board of Directors of Amgen and Thermo Fisher Scientific. He is also a co-founder of T2 Biosystems and Dragonfly Therapeutics, serves as an advisor to several other companies, and is a member of the Harvard Board of Overseers.

Sharp will lead the search for the next director of the Koch Institute, with guidance from noted leaders in MIT’s cancer research community, including Hockfield and Hynes, as well as Angela M. Belcher, head of the Department of Biological Engineering and Jason Mason Crafts Professor; Paula T. Hammond, head of the Department of Chemical Engineering and David H. Koch Professor of Engineering; Amy Keating, professor of biology; Robert S. Langer, David H. Koch Institute Professor; and David M. Sabatini, Professor of Biology and member, Whitehead Institute for Biomedical Research.

“Jacks is a renowned scientist whose personal research has changed the prevention and treatment of cancer,” says Sharp. “His contributions to the creation of the Koch Institute for Integrative Cancer Research and his leadership as its inaugural director have also transformed cancer research at MIT and nationally. By integrating engineers and cancer biologists into a community that shares knowledge and skills, and collaborates with clinical scientists and the private sector, this convergent institute represents the future of biological research in the MIT style.”

After Jacks steps down, he will continue his research in the areas of cancer genetics and immune-oncology and his teaching, while also stewarding the Bridge Project into its second decade.

“It has been a privilege for me to serve as director of the MIT Center for Cancer Research and the Koch Institute for the past two decades and to work alongside many of the brightest minds in cancer research,” says Jacks. “The Koch Institute is a powerhouse of research and innovation, and I look forward to the next generation of leadership in this very special place.”