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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

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    Institute Professor Paula Hammond named to White House science council

    Paula Hammond, an MIT Institute Professor and head of MIT’s Department of Chemical Engineering, has been chosen to serve on the President’s Council of Advisors on Science and Technology (PCAST), the White House announced today.

    The council advises the president on matters involving science, technology, education, and innovation policy. It also provides the White House with scientific and technical information that is needed to inform public policy relating to the U.S. economy, U.S. workers, and national security.

    “For me, this is an exciting opportunity,” Hammond says. “I have always been interested in considering how science can solve important problems in our community, in our country, and globally. It’s very meaningful for me to have a chance to have an advisory role at that level.”

    Hammond is one of 30 members named to the council, which is co-chaired by Frances Arnold, a professor at Caltech, and Maria Zuber, MIT’s vice president for research.

    “Paula is an extraordinary engineer, teacher, and colleague, and President Biden’s decision to appoint her to the council is an excellent one,” Zuber says. “I think about the work ahead of us — not just to restore science and technology to their proper place in policymaking, but also to make sure that they lead to real improvements in the lives of everyone in our country — and I can’t think of anyone better suited to the challenge than Paula.”

    Hammond, whose research as a chemical engineer touches on the fields of both medicine and energy, said she hopes to help address critical issues such as equal access to health care and efforts to mitigate climate change.

    “I’m very excited about the opportunities presented at the interface of engineering and health, and in particular, how we might be able to expand the benefits that we gain from our work to a broader set of communities, so that we’re able to address some of the disparities we see in health, which have been so obvious during the pandemic,” says Hammond, who is also a member of MIT’s Koch Institute for Integrative Cancer Research. “How we might be able to use everything from computational modeling and data science to technological innovation to equalize access to health is one area that I care a lot about.”

    Hammond’s research focuses on developing novel polymers and nanomaterials for a variety of applications in drug delivery, noninvasive imaging, solar cells, and battery technology. Using techniques for building polymers with highly controlled architectures, she has designed drug-delivering nanoparticles that can home in on tumors, as well as polymer films that dramatically improve the efficiency of methanol fuel cells.

    As an MIT faculty member and mentor to graduate students, Hammond has worked to increase opportunities for underrepresented minorities in science and engineering fields. That is a goal she also hopes to pursue in her new role.

    “There’s a lot of work to be done when we look at the low numbers of students of color who are actually going on to science and engineering fields,” she says. “When I think about my work related to increasing diversity in those areas, part of the reason I do it is because that’s where we gain excellence, and where we gain solutions and the foresight to work on the right problems. I also think that it’s important for there to be broad access to the power that science brings.”

    Hammond, who earned both her bachelor’s degree and PhD from MIT, has been a member of the faculty since 1995. She has been a full professor since 2006 and has chaired the Department of Chemical Engineering since 2015. Earlier this year, she was named an Institute Professor, MIT’s highest faculty honor. She is also one of only 25 people who have been elected to all three National Academies — Engineering, Science, and Medicine.

    She has previously served on the U.S. Secretary of Energy Scientific Advisory Board, the NIH Center for Scientific Review Advisory Council, and the Board of Directors of the American Institute of Chemical Engineers. She also chaired or co-chaired two committees that contributed landmark reports on gender and race at MIT: the Initiative for Faculty Race and Diversity, and the Academic and Organizational Relationships Working Group. More