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    Study reveals the benefits and downside of fasting

    Low-calorie diets and intermittent fasting have been shown to have numerous health benefits: They can delay the onset of some age-related diseases and lengthen lifespan, not only in humans but many other organisms.Many complex mechanisms underlie this phenomenon. Previous work from MIT has shown that one way fasting exerts its beneficial effects is by boosting the regenerative abilities of intestinal stem cells, which helps the intestine recover from injuries or inflammation.In a study of mice, MIT researchers have now identified the pathway that enables this enhanced regeneration, which is activated once the mice begin “refeeding” after the fast. They also found a downside to this regeneration: When cancerous mutations occurred during the regenerative period, the mice were more likely to develop early-stage intestinal tumors.“Having more stem cell activity is good for regeneration, but too much of a good thing over time can have less favorable consequences,” says Omer Yilmaz, an MIT associate professor of biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the new study.Yilmaz adds that further studies are needed before forming any conclusion as to whether fasting has a similar effect in humans.“We still have a lot to learn, but it is interesting that being in either the state of fasting or refeeding when exposure to mutagen occurs can have a profound impact on the likelihood of developing a cancer in these well-defined mouse models,” he says.MIT postdocs Shinya Imada and Saleh Khawaled are the lead authors of the paper, which appears today in Nature.Driving regenerationFor several years, Yilmaz’s lab has been investigating how fasting and low-calorie diets affect intestinal health. In a 2018 study, his team reported that during a fast, intestinal stem cells begin to use lipids as an energy source, instead of carbohydrates. They also showed that fasting led to a significant boost in stem cells’ regenerative ability.However, unanswered questions remained: How does fasting trigger this boost in regenerative ability, and when does the regeneration begin?“Since that paper, we’ve really been focused on understanding what is it about fasting that drives regeneration,” Yilmaz says. “Is it fasting itself that’s driving regeneration, or eating after the fast?”In their new study, the researchers found that stem cell regeneration is suppressed during fasting but then surges during the refeeding period. The researchers followed three groups of mice — one that fasted for 24 hours, another one that fasted for 24 hours and then was allowed to eat whatever they wanted during a 24-hour refeeding period, and a control group that ate whatever they wanted throughout the experiment.The researchers analyzed intestinal stem cells’ ability to proliferate at different time points and found that the stem cells showed the highest levels of proliferation at the end of the 24-hour refeeding period. These cells were also more proliferative than intestinal stem cells from mice that had not fasted at all.“We think that fasting and refeeding represent two distinct states,” Imada says. “In the fasted state, the ability of cells to use lipids and fatty acids as an energy source enables them to survive when nutrients are low. And then it’s the postfast refeeding state that really drives the regeneration. When nutrients become available, these stem cells and progenitor cells activate programs that enable them to build cellular mass and repopulate the intestinal lining.”Further studies revealed that these cells activate a cellular signaling pathway known as mTOR, which is involved in cell growth and metabolism. One of mTOR’s roles is to regulate the translation of messenger RNA into protein, so when it’s activated, cells produce more protein. This protein synthesis is essential for stem cells to proliferate.The researchers showed that mTOR activation in these stem cells also led to production of large quantities of polyamines — small molecules that help cells to grow and divide.“In the refed state, you’ve got more proliferation, and you need to build cellular mass. That requires more protein, to build new cells, and those stem cells go on to build more differentiated cells or specialized intestinal cell types that line the intestine,” Khawaled says.Too much of a good thingThe researchers also found that when stem cells are in this highly regenerative state, they are more prone to become cancerous. Intestinal stem cells are among the most actively dividing cells in the body, as they help the lining of the intestine completely turn over every five to 10 days. Because they divide so frequently, these stem cells are the most common source of precancerous cells in the intestine.In this study, the researchers discovered that if they turned on a cancer-causing gene in the mice during the refeeding stage, they were much more likely to develop precancerous polyps than if the gene was turned on during the fasting state. Cancer-linked mutations that occurred during the refeeding state were also much more likely to produce polyps than mutations that occurred in mice that did not undergo the cycle of fasting and refeeding.“I want to emphasize that this was all done in mice, using very well-defined cancer mutations. In humans it’s going to be a much more complex state,” Yilmaz says. “But it does lead us to the following notion: Fasting is very healthy, but if you’re unlucky and you’re refeeding after a fasting, and you get exposed to a mutagen, like a charred steak or something, you might actually be increasing your chances of developing a lesion that can go on to give rise to cancer.”Yilmaz also noted that the regenerative benefits of fasting could be significant for people who undergo radiation treatment, which can damage the intestinal lining, or other types of intestinal injury. His lab is now studying whether polyamine supplements could help to stimulate this kind of regeneration, without the need to fast.“This fascinating study provides insights into the complex interplay between food consumption, stem cell biology, and cancer risk,” says Ophir Klein, a professor of medicine at the University of California at San Francisco and Cedars-Sinai Medical Center, who was not involved in the study. “Their work lays a foundation for testing polyamines as compounds that may augment intestinal repair after injuries, and it suggests that careful consideration is needed when planning diet-based strategies for regeneration to avoid increasing cancer risk.”The research was funded, in part, by a Pew-Stewart Trust Scholar award, the Marble Center for Cancer Nanomedicine, the Koch Institute-Dana Farber/Harvard Cancer Center Bridge Project, and the MIT Stem Cell Initiative. More

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    Angela Belcher delivers 2023 Dresselhaus Lecture on evolving organisms for new nanomaterials

    “How do we get to making nanomaterials that haven’t been evolved before?” asked Angela Belcher at the 2023 Mildred S. Dresselhaus Lecture at MIT on Nov. 20. “We can use elements that biology has already given us.”

    The combined in-person and virtual audience of over 300 was treated to a light-up, 3D model of M13 bacteriophage, a virus that only infects bacteria, complete with a pull-out strand of DNA. Belcher used the feather-boa-like model to show how her research group modifies the M13’s genes to add new DNA and peptide sequences to template inorganic materials.

    “I love controlling materials at the nanoscale using biology,” said Belcher, the James Mason Crafts Professor of Biological Engineering, materials science professor, and of the Koch Institute of Integrative Cancer Research at MIT. “We all know if you control materials at the nanoscale and you can start to tune them, then you can have all kinds of different applications.” And the opportunities are indeed vast — from building batteries, fuel cells, and solar cells to carbon sequestration and storage, environmental remediation, catalysis, and medical diagnostics and imaging.

    Belcher sprinkled her talk with models and props, lined up on a table at the front of the 10-250 lecture hall, to demonstrate a wide variety of concepts and projects made possible by the intersection of biology and nanotechnology.

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    2023 Mildred S. Dresselhaus Lecture: Angela BelcherVideo: MIT.nano

    Energy storage and environment

    “How do you go from a DNA sequence to a functioning battery?” posed Belcher. Grabbing a model of a large carbon nanotube, she explained how her group engineered a phage to pick up carbon nanotubes that would wind all the way around the virus and then fill in with different cathode or anode materials to make nanowires for battery electrodes.

    How about using the M13 bacteriophage to improve the environment? Belcher referred to a project by former student Geran Zhang PhD ’19 that proved the virus can be modified for this context, too. He used the phage to template high-surface-area, carbon-based materials that can grab small molecules and break them down, Belcher said, opening a realm of possibilities from cleaning up rivers to developing chemical warfare agents to combating smog.

    Belcher’s lab worked with the U.S. Army to produce protective clothing and masks made of these carbon-based virus nanofibers. “We went from five liters in our lab to a thousand liters, then 10,000 liters in the army labs where we’re able to make kilograms of the material,” Belcher said, stressing the importance of being able to test and prototype at scale.

    Imaging tools and therapeutics in cancer

    In the area of biomedical imaging, Belcher explained, a lot less is known in near-infrared imaging — imaging in wavelengths above 1,000 nanometers — than other imaging techniques, yet with near-infrared scientists can see much deeper inside the body. Belcher’s lab built their own systems to image at these wavelengths. The third generation of this system provides real-time, sub-millimeter optical imaging for guided surgery.

    Working with Sangeeta Bhatia, the John J. and Dorothy Wilson Professor of Engineering, Belcher used carbon nanotubes to build imaging tools that find tiny tumors during surgery that doctors otherwise would not be able to see. The tool is actually a virus engineered to carry with it a fluorescent, single-walled carbon nanotube as it seeks out the tumors.

    Nearing the end of her talk, Belcher presented a goal: to develop an accessible detection and diagnostic technology for ovarian cancer in five to 10 years.

    “We think that we can do it,” Belcher said. She described her students’ work developing a way to scan an entire fallopian tube, as opposed to just one small portion, to find pre-cancer lesions, and talked about the team of MIT faculty, doctors, and researchers working collectively toward this goal.

    “Part of the secret of life and the meaning of life is helping other people enjoy the passage of time,” said Belcher in her closing remarks. “I think that we can all do that by working to solve some of the biggest issues on the planet, including helping to diagnose and treat ovarian cancer early so people have more time to spend with their family.”

    Honoring Mildred S. Dresselhaus

    Belcher was the fifth speaker to deliver the Dresselhaus Lecture, an annual event organized by MIT.nano to honor the late MIT physics and electrical engineering Institute Professor Mildred Dresselhaus. The lecture features a speaker from anywhere in the world whose leadership and impact echo Dresselhaus’s life, accomplishments, and values.

    “Millie was and is a huge hero of mine,” said Belcher. “Giving a lecture in Millie’s name is just the greatest honor.”

    Belcher dedicated the talk to Dresselhaus, whom she described with an array of accolades — a trailblazer, a genius, an amazing mentor, teacher, and inventor. “Just knowing her was such a privilege,” she said.

    Belcher also dedicated her talk to her own grandmother and mother, both of whom passed away from cancer, as well as late MIT professors Susan Lindquist and Angelika Amon, who both died of ovarian cancer.

    “I’ve been so fortunate to work with just the most talented and dedicated graduate students, undergraduate students, postdocs, and researchers,” concluded Belcher. “It has been a pure joy to be in partnership with all of you to solve these very daunting problems.” More

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    Exploring the links between diet and cancer

    Every three to five days, all of the cells lining the human intestine are replaced. That constant replenishment of cells helps the intestinal lining withstand the damage caused by food passing through the digestive tract.

    This rapid turnover of cells relies on intestinal stem cells, which give rise to all of the other types of cells found in the intestine. Recent research has shown that those stem cells are heavily influenced by diet, which can help keep them healthy or stimulate them to become cancerous.

    “Low-calorie diets such as fasting and caloric restriction can have antiaging effects and antitumor effects, and we want to understand why that is. On the other hand, diets that lead to obesity can promote diseases of aging, such as cancer,” says Omer Yilmaz, the Eisen and Chang Career Development Associate Professor of Biology at MIT.

    For the past decade, Yilmaz has been studying how different diets and environmental conditions affect intestinal stem cells, and how those factors can increase the risk of cancer and other diseases. This work could help researchers develop new ways to improve gastrointestinal health, either through dietary interventions or drugs that mimic the beneficial effects of certain diets, he says. 

    “Our findings have raised the possibility that fasting interventions, or small molecules that mimic the effects of fasting, might have a role in improving intestinal regeneration,” says Yilmaz, who is also a member of MIT’s Koch Institute for Integrative Cancer Research.

    A clinical approach

    Yilmaz’s interest in disease and medicine arose at an early age. His father practiced internal medicine, and Yilmaz spent a great deal of time at his father’s office after school, or tagging along at the hospital where his father saw patients.

    “I was very interested in medicines and how medicines were used to treat diseases,” Yilmaz recalls. “He’d ask me questions, and many times I wouldn’t know the answer, but he would encourage me to figure out the answers to his questions. That really stimulated my interest in biology and in wanting to become a doctor.”

    Knowing that he wanted to go into medicine, Yilmaz applied and was accepted to an eight-year, combined bachelor’s and MD program at the University of Michigan. As an undergraduate, this gave him the freedom to explore areas of interest without worrying about applying to medical school. While majoring in biochemistry and physics, he did undergraduate research in the field of protein folding.

    During his first year of medical school, Yilmaz realized that he missed doing research, so he decided to apply to the MD/PhD program at the University of Michigan. For his PhD research, he studied blood-forming stem cells and identified new markers that allowed such cells to be more easily isolated from the bone marrow.

    “This was important because there’s a lot of interest in understanding what makes a stem cell a stem cell, and how much of it is an internal program versus signals from the microenvironment,” Yilmaz says.

    After finishing his PhD and MD, he thought about going straight into research and skipping a medical residency, but ended up doing a residency in pathology at Massachusetts General Hospital. During that time, he decided to switch his research focus from blood-forming stem cells to stem cells found in the gastrointestinal tract.

    “The GI tract seemed very interesting because in contrast to the bone marrow, we knew very little about the identity of GI stem cells,” Yilmaz says. “I knew that once GI stem cells were identified, there’d be a lot of interesting questions about how they respond to diet and how they respond to other environmental stimuli.”

    Dietary questions

    To delve into those questions, Yilmaz did postdoctoral research at the Whitehead Institute, where he began investigating the connections between stem cells, metabolism, diet, and cancer.

    Because intestinal stem cells are so long-lived, they are more likely to accumulate genetic mutations that make them susceptible to becoming cancerous. At the Whitehead Institute, Yilmaz began studying how different diets might influence this vulnerability to cancer, a topic that he carried into his lab at MIT when he joined the faculty in 2014.

    One question his lab has been exploring is why low-calorie diets often have protective effects, including a boost in longevity — a phenomenon that has been seen in many studies in animals and humans.

    In a 2018 study, his lab found that a 24-hour fast dramatically improves stem cells’ ability to regenerate. This effect was seen in both young and aged mice, suggesting that even in old age, fasting or drugs that mimic the effects of fasting could have a beneficial effect.

    On the flip side, Yilmaz is also interested in why a high-fat diet appears to promote the development of cancer, especially colorectal cancer. In a 2016 study, he found that when mice consume a high-fat diet, it triggers a significant increase in the number of intestinal stem cells. Also, some non-stem-cell populations begin to resemble stem cells in their behavior. “The upshot of these changes is that both stem cells and non-stem-cells can give rise to tumors in a high-fat diet state,” Yilmaz says.

    To help with these studies, Yilmaz’s lab has developed a way to use mouse or human intestinal stem cells to generate miniature intestines or colons in cell culture. These “organoids” can then be exposed to different nutrients in a very controlled setting, allowing researchers to analyze how different diets affect the system.

    Recently, his lab adapted the system to allow them to expand their studies to include the role of immune cells, fibroblasts, and other supportive cells found in the microenvironment of stem cells. “It would be remiss of us to focus on just one cell type,” Yilmaz says. “We’re looking at how these different dietary interventions impact the entire stem cell neighborhood.”

    While Yilmaz spends most of his time running his lab at MIT, he also devotes six to eight weeks per year to his work at MGH, where he is an associate pathologist focusing on gastrointestinal pathology.

    “I enjoy my clinical work, and it always reminds me about the importance of the research we do,” he says. “Seeing colon cancer and other GI cancers under the microscope, and seeing their complexity, reminds me of the importance of our mission to figure out how we can prevent these cancers from forming.” More

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    Paula Hammond wins faculty’s Killian Award for 2023-24

    Paula Hammond, a leading innovator in nanotechnology and head of MIT’s Department of Chemical Engineering, has been named the recipient of the 2023-2024 James R. Killian Jr. Faculty Achievement Award.

    Hammond, an MIT Institute Professor, was honored for her work designing novel polymers and nanomaterials, which have extensive applications in fields including medicine and energy.

    “Professor Hammond is a pioneer in nanotechnology research, with a program that spans from basic science to translational research in medicine and energy. She has introduced new approaches for the design and development of complex drug delivery systems for cancer treatment and non-invasive imaging,” according to the award citation, which was read at the May 17 faculty meeting by Laura Kiessling, the chair of the Killian Award Selection Committee and the Novartis Professor of Chemistry at MIT.

    Established in 1971 to honor MIT’s 10th president, James Killian, the Killian Award recognizes extraordinary professional achievements by an MIT faculty member.

    “I’ve been to past Killian Award lectures, and I’ve always thought these were the ultimate achievers at MIT in terms of their work and their science,” Hammond says. “I am incredibly honored and overwhelmed to be considered even close to a part of that group.”

    Hammond, who earned her bachelor’s degree from MIT in 1984, worked as an engineer before returning to the Institute four years later to earn a PhD, which she received in 1993. After two years as a postdoc at Harvard University, she returned to MIT again as a faculty member in 1995.

    “In a world where it isn’t always cool to be heavy into your science and your work, MIT was a place where I felt like I could just be completely myself, and that was an amazing thing,” she says.

    Since joining the faculty, Hammond has pioneered techniques for creating thin polymer films and other materials using layer-by-layer assembly. This approach can be used to build polymers with highly controlled architectures by alternately exposing a surface to positively and negatively charged particles.

    Hammond’s lab uses this technique to design materials for many different applications, including drug delivery, regenerative medicine, noninvasive imaging, and battery technology.

    Her accomplishments include designing nanoparticles that can zoom in on tumors and release their cargo when they associate with cancer cells. She has also developed nanoparticles and thin polymer films that can carry multiple drugs to a specific site and release the drugs in a controlled or staggered fashion. In recent years, much of that work has focused on potential treatments and diagnostics for ovarian cancer.

    “We’ve really had a focus on ovarian cancer over the past several years. My hope is that our work will move us in the direction of understanding how we can treat ovarian cancer, and, in collaboration with my colleagues, how we can detect it more effectively,” says Hammond, who is a member of MIT’s Koch Institute for Integrative Cancer Research.

    The award committee also cited Hammond’s record of service, both to MIT and the national scientific community. She currently serves on the President’s Council of Advisors on Science and Technology, and she is a former member of the U.S. Secretary of Energy Scientific Advisory Board. At MIT, Hammond chaired the Initiative on Faculty Race and Diversity, and co-chaired the Academic and Professional Relationships Working Group and the Implementation Team of the MIT response to the National Academies’ report entitled “Sexual Harassment of Women.”

    Among her many honors, Hammond is one of only 25 scientists who have been elected to the National Academies of Engineering, Sciences, and Medicine.

    Hammond has also been recognized for her dedication to teaching and mentoring. As a reflection of her excellence in those areas, Hammond was awarded the Irwin Sizer Award for Significant Improvements to MIT Education, the Henry Hill Lecturer Award in 2002, and the Junior Bose Faculty Award in 2000. She also co-chaired the recent Ad Hoc Committee on Faculty Advising and Mentoring, and has been selected as a “Committed to Caring” honoree for her work mentoring students and postdocs in her research group.

    “The Selection Committee is delighted to have this opportunity to honor Professor Paula Hammond, not only for her tremendous professional achievements and contributions, but also for her genuine warmth and humanity, her thoughtfulness and effective leadership, and her empathy and ethics. She is someone worth emulating. Indeed, simply put, she is the best of us,” the award committee wrote in its citation. More

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    Recycling plastics from research labs

    In 2019, MIT’s Environment, Health, and Safety (EHS) Office collaborated with several research labs in the Department of Biology to determine the feasibility of recycling clean lab plastics. Based on early successes with waste isolation and plastics collection, EHS collaborated with GreenLabs Recycling, a local startup, to remove and recycle lab plastics from campus. It was a huge success.

    Today, EHS spearheads the campus Lab Plastics Recycling Program, and its EHS technicians regularly gather clean lab plastics from 212 MIT labs, transferring them to GreenLabs for recycling. Since its pilot stage, the number of labs participating in the program has grown, increasing the total amount of plastic gathered and recycled. In 2020, EHS collected 170 pounds of plastic waste per week from participating labs. That increased to 250 pounds per week in 2021. In 2022, EHS collected a total of 19,000 pounds, or 280 pounds of plastic per week.

    Joanna Buchthal, a research assistant with the MIT Media Lab, indicates that, prior to joining the EHS Lab Plastics Recycling Program, “our laboratory was continuously troubled by the substantial volume of plastic waste we produced and disheartened by our inability to recycle it. We frequently addressed this issue during our group meetings and explored various ways to repurpose our waste, yet we never arrived at a viable solution.”

    The EHS program now provides a solution to labs facing similar challenges with plastics use. After pickup and removal, the plastics are shredded and sold as free stock for injection mold product manufacturing. Buchthal says, “My entire lab is delighted to recycle our used tip boxes and transform them into useful items for other labs!”

    Recently, GreenLabs presented EHS with a three-gallon bucket that local manufacturers produced from 100 percent recycled plastic gathered from MIT labs. No fillers or additives were used in its production.

    Keeping it clean

    The now-growing EHS service and operation started as a pilot. In June 2019, MIT restricted which lab-generated items could be placed in single-stream recycling. MIT’s waste vendors were no longer accepting possibly contaminated waste, such as gloves, pipette tip boxes, bottles, and other plastic waste typically generated in biological research labs. The waste vendors would audit MIT’s single-stream recycling and reject items if they observed any contamination.

    Facing these challenges, the EHS coordinator for biology, John Fucillo, and several EHS representatives from the department met with EHS staff to brainstorm potential recycling solutions. Ensuring the decontamination of the plastic and coordinating its removal in an efficient way were the primary challenges for the labs, says Fucillo, who shared his and lab members’ concerns about the amount of plastic being thrown away with Mitch Galanek, EHS associate director for the Radiation Protection Program. Galanek says, “I immediately recognized the frustration expressed by John and other lab contacts as an opportunity to collaborate.”

    In July 2019, Galanek and a team of EHS technicians began segregating and collecting clean plastic waste from several labs within the biology department. EHS provided the labs with collection containers, and its technicians managed the waste removal over a four-month period, which produced a snapshot of the volume and type of waste generated. An audit of the waste determined that approximately 80 percent of the clean plastic waste generated was empty pipette tip boxes and conical tube racks.

    Based on these data, EHS launched a lab plastics recycling pilot program in November 2019. Labs from the Department of Biology and the Koch Institute for Integrative Cancer Research were invited to participate by recycling their clean, uncontaminated pipette tip boxes and conical tube racks. In addition to providing these labs with collection boxes and plastic liners, EHS also developed an online waste collection request tool to submit plastic pickup requests. EHS also collected the waste containers once they were full.

    Assistant professor of biology Seychelle Vos joined the pilot program as soon as she started her lab in fall 2019. Vos shares that “we already use pipette tips boxes that produce minimal waste, and this program allows us to basically recycle any part of the box except for tips. Pipette boxes are a significant source of plastic waste. This program helps us to be more environmentally and climate friendly.” 

    Given the increased participation in the program, EHS technician Dave Pavone says that plastic pickup is now a “regular component of our work schedules.”

    Together, the EHS technicians, commonly known as “techs,” manage the pickup of nearly 300 plastic collection containers across campus. Normand Desrochers, one of the EHS techs, shares that each morning he plans his pickup route “to get the job done efficiently.” While weekly pickups are a growing part of their schedules, Desrochers notes that everyone has been “super appreciative in what we do for their labs. And what we do makes their job that much easier, being able to focus on their research.”

    Barbara Karampalas, a lab operations manager within the Department of Biological Engineering, is one of many to express appreciation for the program: “We have a fairly large lab with 35 researchers, so we generate a lot of plastic waste … [and] knowing how many tip boxes we were using concerned me. I really appreciate the effort EHS has made to implement this program to help us reduce our impact on the environment.” The program also “makes people in the lab more aware of the issue of plastic waste and MIT’s commitment to reduce its impact on the environment,” says Karampalas.

    Looking ahead

    MIT labs continue to enthusiastically embrace the EHS Lab Plastics Recycling Program: 112 faculty across 212 labs are currently participating in the program. While only empty pipette tip boxes and conical tube racks are currently collected, EHS is exploring which lab plastics could be manufactured into products for use in the labs and repeatedly recycled. Specifically, the EHS Office is considering whether recycled plastic could be used to produce secondary containers for collecting hazardous waste and benchtop transfer containers used for collecting medical waste. As Seychelle notes, “Most plastics cannot be recycled in the current schemes due to their use in laboratory science.”

    Says Fucillo, “Our hope is that this program can be expanded to include other products which could be recycled from the wet labs.” John MacFarlane, research engineer and EHS coordinator for civil and environmental engineering, echoes this sentiment: “With plastic recycling facing economic constraints, this effort by the Institute deserves to be promoted and, hopefully, expanded.”

    “Having more opportunities to recycle ’biologically clean’ plastics would help us have a smaller carbon footprint,” agrees Vos. “We love this program and hope it expands further!”

    MIT labs interested in participating in the EHS Lab Plastics Recycling Program can contact pipetip@mit.edu to learn more. More

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    Microparticles could help prevent vitamin A deficiency

    Vitamin A deficiency is the world’s leading cause of childhood blindness, and in severe cases, it can be fatal. About one-third of the global population of preschool-aged children suffer from this vitamin deficiency, which is most prevalent in sub-Saharan Africa and South Asia.

    MIT researchers have now developed a new way to fortify foods with vitamin A, which they hope could help to improve the health of millions of people around the world. In a new study, they showed that encapsulating vitamin A in a protective polymer prevents the nutrient from being broken down during cooking or storage.

    “Vitamin A is a very important micronutrient, but it’s an unstable molecule,” says Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research. “We wanted to see if our encapsulated vitamin A could fortify a food vehicle like bouillon cubes or flour, throughout storage and cooking, and whether the vitamin A could remain biologically active and be absorbed.”

    In a small clinical trial, the researchers showed that when people ate bread fortified with encapsulated vitamin A, the bioavailability of the nutrient was similar to when they consumed vitamin A on its own. The technology has been licensed to two companies that hope to develop it for use in food products.

    “This is a study that our team is really excited about because it shows that everything we did in test tubes and animals works safely and effectively in humans,” says Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute. “We hope this opens the door for someday helping millions, if not billions, of people in the developing world.”

    Jaklenec and Langer are the senior authors of the new study, which appears this week in the Proceedings of the National Academy of Sciences. The paper’s lead author is former MIT postdoc Wen Tang, who is now an associate professor at South China University of Technology.

    Nutrient stability

    Vitamin A is critical not only for vision but also the functioning of the immune system and organs such as the heart and lungs. Efforts to add vitamin A to bread or other foods such as bouillon cubes, which are commonly consumed in West African countries, have been largely unsuccessful because the vitamin breaks down during storage or cooking.

    In a 2019 study, the MIT team showed that they could use a polymer called BMC to encapsulate nutrients, including iron, vitamin A, and several others. They showed that this protective coating improved the shelf life of the nutrients, and that people who consumed bread fortified with encapsulated iron were able to absorb the iron.

    BMC is classified by the FDA as “generally regarded as safe,” and is already used in coatings for drugs and dietary supplements. In the new study, the researchers focused on using this polymer to encapsulate vitamin A, a nutrient that is very sensitive to temperature and ultraviolet light.

    Using an industrial process known as a spinning disc process, the researchers mixed vitamin A with the polymer to form particles 100 to 200 microns in diameter. They also coated the particles with starch, which prevents them from sticking to each other.

    The researchers found that vitamin A encapsulated in the polymer particles were more resistant to degradation by intense light, high temperatures, or boiling water. Under those conditions, much more vitamin A remained active than when the vitamin A was free or when it was delivered in a form called VitA 250, which is currently the most stable form of vitamin A used for food fortification.

    The researchers also showed that the encapsulated particles could be easily incorporated into flour or bouillon cubes. To test how well they would survive long-term storage, the researchers exposed the cubes to harsh conditions, as recommended by the World Health Organization: 40 degrees Celsius (104 degrees Fahrenheit) and 75 percent humidity. Under those conditions, the encapsulated vitamin A was much more stable than other forms of vitamin A. 

    “The enhanced stability of vitamin A with our technology can ensure that the vitamin A-fortified food does provide the recommended daily uptake of vitamin A, even after long-term storage in a hot humidified environment, and cooking processes such as boiling or baking,” Tang says. “People who are suffering from vitamin A deficiency and want to get vitamin A through fortified food will benefit, without changing their daily routines, and without wondering how much vitamin A is still in the food.”

    Vitamin absorption

    When the researchers cooked their encapsulated particles and then fed them to animals, they found that 30 percent of the vitamin A was absorbed, the same as free uncooked vitamin A, compared to about 3 percent of free vitamin A that had been cooked.

    Working with Biofortis, a company that does dietary clinical testing, the researchers then evaluated how well vitamin A was absorbed in people who ate foods fortified with the particles. For this study, the researchers incorporated the particles into bread, then measured vitamin A levels in the blood over a 24-hour period after the bread was consumed. They found that when vitamin A was encapsulated in the BMC polymer, it was absorbed from the food at levels comparable to free vitamin A, indicating that it is readily released in bioactive form.

    Two companies have licensed the technology and are focusing on developing products fortified with vitamin A and other nutrients. A benefit corporation called Particles for Humanity, funded by the Bill and Melinda Gates Foundation, is working with partners in Africa to incorporate this technology into existing fortification efforts. Another company called VitaKey, founded by Jaklenec, Langer, and others, is working on using this approach to add nutrients to a variety of foods and beverages.

    The research was funded by the Bill and Melinda Gates Foundation. Other authors of the paper include Jia Zhuang, Aaron Anselmo, Xian Xu, Aranda Duan, Ruojie Zhang, James Sugarman, Yingying Zeng, Evan Rosenberg, Tyler Graf, Kevin McHugh, Stephany Tzeng, Adam Behrens, Lisa Freed, Lihong Jing, Surangi Jayawardena, Shelley Weinstock, Xiao Le, Christopher Sears, James Oxley, John Daristotle, and Joe Collins. More

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    MIT PhD students shed light on important water and food research

    One glance at the news lately will reveal countless headlines on the dire state of global water and food security. Pollution, supply chain disruptions, and the war in Ukraine are all threatening water and food systems, compounding climate change impacts from heat waves, drought, floods, and wildfires.

    Every year, MIT’s Abdul Latif Jameel Water and Food Systems Lab (J-WAFS) offers fellowships to outstanding MIT graduate students who are working on innovative ways to secure water and food supplies in light of these urgent worldwide threats. J-WAFS announced this year’s fellowship recipients last April. Aditya Ghodgaonkar and Devashish Gokhale were awarded Rasikbhai L. Meswani Fellowships for Water Solutions, which are made possible by a generous gift from Elina and Nikhil Meswani and family. James Zhang, Katharina Fransen, and Linzixuan (Rhoda) Zhang were awarded J-WAFS Fellowships for Water and Food Solutions. The J-WAFS Fellowship for Water and Food Solutions is funded in part by J-WAFS Research Affiliate companies: Xylem, Inc., a water technology company, and GoAigua, a company leading the digital transformation of the water industry.

    The five fellows were each awarded a stipend and full tuition for one semester. They also benefit from mentorship, networking connections, and opportunities to showcase their research.

    “This year’s cohort of J-WAFS fellows show an indefatigable drive to explore, create, and push back boundaries,” says John H. Lienhard, director of J-WAFS. “Their passion and determination to create positive change for humanity are evident in these unique video portraits, which describe their solutions-oriented research in water and food,” Lienhard adds.

    J-WAFS funder Community Jameel recently commissioned video portraitures of each student that highlight their work and their inspiration to solve challenges in water and food. More about each J-WAFS fellow and their research follows.

    Play video

    Katharina Fransen

    In Professor Bradley Olsen’s lab in the Department of Chemical Engineering, Katharina Fransen works to develop biologically-based, biodegradable plastics which can be used for food packing that won’t pollute the environment. Fransen, a third-year PhD student, is motivated by the challenge of protecting the most vulnerable global communities from waste generated by the materials that are essential to connecting them to the global food supply. “We can’t ensure that all of our plastic waste gets recycled or reused, and so we want to make sure that if it does escape into the environment it can degrade, and that’s kind of where a lot of my research really comes in,” says Fransen. Most of her work involves creating polymers, or “really long chains of chemicals,” kind of like the paper rings a lot of us looped into chains as kids, Fransen explains. The polymers are optimized for food packaging applications to keep food fresher for longer, preventing food waste. Fransen says she finds the work “really interesting from the scientific perspective as well as from the idea that [she’s] going to make the world a little better with these new materials.” She adds, “I think it is both really fulfilling and really exciting and engaging.”

    Play video

    Aditya Ghodgaonkar

    “When I went to Kenya this past spring break, I had an opportunity to meet a lot of farmers and talk to them about what kind of maintenance issues they face,” says Aditya Ghodgaonkar, PhD candidate in the Department of Mechanical Engineering. Ghodgaonkar works with Associate Professor Amos Winter in the Global Engineering and Research (GEAR) Lab, where he designs hydraulic components for drip irrigation systems to make them water-efficient, off-grid, inexpensive, and low-maintenance. On his trip to Kenya, Ghodgaonkar gained firsthand knowledge from farmers about a common problem they encounter: clogging of drip irrigation emitters. He learned that clogging can be an expensive technical challenge to diagnose, mitigate, and resolve. He decided to focus his attention on designing emitters that are resistant to clogging, testing with sand and passive hydrodynamic filtration back in the lab at MIT. “I got into this from an academic standpoint,” says Ghodgaonkar. “It is only once I started working on the emitters, spoke with industrial partners that make these emitters, spoke with farmers, that I really truly appreciated the impact of what we’re doing.”

    Play video

    Devashish Gokhale

    Devashish Gokhale is a PhD student advised by Professor Patrick Doyle in the Department of Chemical Engineering. Gokhale’s commitment to global water security stems from his childhood in Pune, India, where both flooding and drought can occur depending on the time of year. “I’ve had these experiences where there’s been too much water and also too little water” he recalls. At MIT, Gokhale is developing cost-effective, sustainable, and reusable materials for water treatment with a focus on the elimination of emerging contaminants and low-concentration pollutants like heavy metals. Specifically, he works on making and optimizing polymeric hydrogel microparticles that can absorb micropollutants. “I know how important it is to do something which is not just scientifically interesting, but something which is impactful in a real way,” says Gokhale. Before starting a research project he asks himself, “are people going to be able to afford this? Is it really going to reach the people who need it the most?” Adding these constraints in the beginning of the research process sometimes makes the problem more difficult to solve, but Gokhale notes that in the end, the solution is much more promising.

    Play video

    James Zhang

    “We don’t really think much about it, it’s transparent, odorless, we just turn on our sink in many parts of the world and it just flows through,” says James Zhang when talking about water. Yet he notes that “many other parts of the world face water scarcity and this will only get worse due to global climate change.” A PhD student in the Department of Mechanical Engineering, Zhang works in the Nano Engineering Laboratory with Professor Gang Chen. Zhang is working on a technology that uses light-induced evaporation to clean water. He is currently investigating the fundamental properties of how light at different wavelengths interacts with liquids at the surface, particularly with brackish water surfaces. With strong theoretical and experimental components, his research could lead to innovations in desalinating water at high energy efficiencies. Zhang hopes that the technology can one day “produce lots of clean water for communities around the world that currently don’t have access to fresh water,” and create a new appreciation for this common liquid that many of us might not think about on a day-to-day basis.

    Play video

    Linzixuan (Rhoda) Zhang

    “Around the world there are about 2 billion people currently suffering from micronutrient deficiency because they do not have access to very healthy, very fresh food,” says chemical engineering PhD candidate Linzixuan (Rhoda) Zhang. This fact led Zhang to develop a micronutrient delivery platform that fortifies foods with essential vitamins and nutrients. With her advisors, Professor Robert Langer and Research Scientist Ana Jaklenec, Zhang brings biomedical engineering approaches to global health issues. Zhang says that “one of the most serious problems is vitamin A deficiency, because vitamin A is not very stable.” She goes on to explain that although vitamin A is present in different vegetables, when the vegetables are cooked, vitamin A can easily degrade. Zhang helped develop a group of biodegradable polymers that can stabilize micronutrients under cooking and storage conditions. With this technology, vitamin A, for example, could be encapsulated and effectively stabilized under boiling water. The platform has also shown efficient release in a simulation of the stomach environment. Zhang says it is the “little, tiny steps every day that are pushing us forward to the final impactful product.” More

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    How diet affects tumors

    In recent years, there has been some evidence that dietary interventions can help to slow the growth of tumors. A new study from MIT, which analyzed two different diets in mice, reveals how those diets affect cancer cells, and offers an explanation for why restricting calories may slow tumor growth.

    The study examined the effects of a calorically restricted diet and a ketogenic diet in mice with pancreatic tumors. While both of these diets reduce the amount of sugar available to tumors, the researchers found that only the calorically restricted diet reduced the availability of fatty acids, and this was linked to a slowdown in tumor growth.

    The findings do not suggest that cancer patients should try to follow either of these diets, the researchers say. Instead, they believe the findings warrant further study to determine how dietary interventions might be combined with existing or emerging drugs to help patients with cancer.

    “There’s a lot of evidence that diet can affect how fast your cancer progresses, but this is not a cure,” says Matthew Vander Heiden, director of MIT’s Koch Institute for Integrative Cancer Research and the senior author of the study. “While the findings are provocative, further study is needed, and individual patients should talk to their doctor about the right dietary interventions for their cancer.”

    MIT postdoc Evan Lien is the lead author of the paper, which appears today in Nature.

    Metabolic mechanism

    Vander Heiden, who is also a medical oncologist at Dana-Farber Cancer Institute, says his patients often ask him about the potential benefits of various diets, but there is not enough scientific evidence available to offer any definitive advice. Many of the dietary questions that patients have focus on either a calorie-restricted diet, which reduces calorie consumption by 25 to 50 percent, or a ketogenic diet, which is low in carbohydrates and high in fat and protein.

    Previous studies have suggested that a calorically restricted diet might slow tumor growth in some contexts, and such a diet has been shown to extend lifespan in mice and many other animal species. A smaller number of studies exploring the effects of a ketogenic diet on cancer have produced inconclusive results.

    “A lot of the advice or cultural fads that are out there aren’t necessarily always based on very good science,” Lien says. “It seemed like there was an opportunity, especially with our understanding of cancer metabolism having evolved so much over the past 10 years or so, that we could take some of the biochemical principles that we’ve learned and apply those concepts to understanding this complex question.”

    Cancer cells consume a great deal of glucose, so some scientists had hypothesized that either the ketogenic diet or calorie restriction might slow tumor growth by reducing the amount of glucose available. However, the MIT team’s initial experiments in mice with pancreatic tumors showed that calorie restriction has a much greater effect on tumor growth than the ketogenic diet, so the researchers suspected that glucose levels were not playing a major role in the slowdown.

    To dig deeper into the mechanism, the researchers analyzed tumor growth and nutrient concentration in mice with pancreatic tumors, which were fed either a normal, ketogenic, or calorie-restricted diet. In both the ketogenic and calorie-restricted mice, glucose levels went down. In the calorie-restricted mice, lipid levels also went down, but in mice on the ketogenic diet, they went up.

    Lipid shortages impair tumor growth because cancer cells need lipids to construct their cell membranes. Normally, when lipids aren’t available in a tissue, cells can make their own. As part of this process, they need to maintain the right balance of saturated and unsaturated fatty acids, which requires an enzyme called stearoyl-CoA desaturase (SCD). This enzyme is responsible for converting saturated fatty acids into unsaturated fatty acids.

    Both calorie-restricted and ketogenic diets reduce SCD activity, but mice on the ketogenic diet had lipids available to them from their diet, so they didn’t need to use SCD. Mice on the calorie-restricted diet, however, couldn’t get fatty acids from their diet or produce their own. In these mice, tumor growth slowed significantly, compared to mice on the ketogenic diet.

    “Not only does caloric restriction starve tumors of lipids, it also impairs the process that allows them to adapt to it. That combination is really contributing to the inhibition of tumor growth,” Lien says.

    Dietary effects

    In addition to their mouse research, the researchers also looked at some human data. Working with Brian Wolpin, an oncologist at Dana-Farber Cancer Institute and an author of the paper, the team obtained data from a large cohort study that allowed them to analyze the relationship between dietary patterns and survival times in pancreatic cancer patients. From that study, the researchers found that the type of fat consumed appears to influence how patients on a low-sugar diet fare after a pancreatic cancer diagnosis, although the data are not complete enough to draw any conclusions about the effect of diet, the researchers say.

    Although this study showed that calorie restriction has beneficial effects in mice, the researchers say they do not recommend that cancer patients follow a calorie-restricted diet, which is difficult to maintain and can have harmful side effects. However, they believe that cancer cells’ dependence on the availability of unsaturated fatty acids could be exploited to develop drugs that might help slow tumor growth.

    One possible therapeutic strategy could be inhibition of the SCD enzyme, which would cut off tumor cells’ ability to produce unsaturated fatty acids.

    “The purpose of these studies isn’t necessarily to recommend a diet, but it’s to really understand the underlying biology,” Lien says. “They provide some sense of the mechanisms of how these diets work, and that can lead to rational ideas on how we might mimic those situations for cancer therapy.”

    The researchers now plan to study how diets with a variety of fat sources — including plant or animal-based fats with defined differences in saturated, monounsaturated, and polyunsaturated fatty acid content — alter tumor fatty acid metabolism and the ratio of unsaturated to saturated fatty acids.

    The research was funded by the Damon Runyon Cancer Research Foundation, the National Institutes of Health, the Lustgarten Foundation, the Dana-Farber Cancer Institute Hale Family Center for Pancreatic Cancer Research, Stand Up to Cancer, the Pancreatic Cancer Action Network, the Noble Effort Fund, the Wexler Family Fund, Promises for Purple, the Bob Parsons Fund, the Emerald Foundation, the Howard Hughes Medical Institute, the MIT Center for Precision Cancer Medicine, and the Ludwig Center at MIT. More