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    Would you like that coffee with iron?

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    Around the world, about 2 billion people suffer from iron deficiency, which can lead to anemia, impaired brain development in children, and increased infant mortality.To combat that problem, MIT researchers have come up with a new way to fortify foods and beverages with iron, using small crystalline particles. These particles, known as metal-organic frameworks, could be sprinkled on food, added to staple foods such as bread, or incorporated into drinks like coffee and tea.“We’re creating a solution that can be seamlessly added to staple foods across different regions,” says Ana Jaklenec, a principal investigator at MIT’s Koch Institute for Integrative Cancer Research. “What’s considered a staple in Senegal isn’t the same as in India or the U.S., so our goal was to develop something that doesn’t react with the food itself. That way, we don’t have to reformulate for every context — it can be incorporated into a wide range of foods and beverages without compromise.”The particles designed in this study can also carry iodine, another critical nutrient. The particles could also be adapted to carry important minerals such as zinc, calcium, or magnesium.“We are very excited about this new approach and what we believe is a novel application of metal-organic frameworks to potentially advance nutrition, particularly in the developing world,” says Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute.Jaklenec and Langer are the senior authors of the study, which appears today in the journal Matter. MIT postdoc Xin Yang and Linzixuan (Rhoda) Zhang PhD ’24 are the lead authors of the paper.Iron stabilizationFood fortification can be a successful way to combat nutrient deficiencies, but this approach is often challenging because many nutrients are fragile and break down during storage or cooking. When iron is added to foods, it can react with other molecules in the food, giving the food a metallic taste.In previous work, Jaklenec’s lab has shown that encapsulating nutrients in polymers can protect them from breaking down or reacting with other molecules. In a small clinical trial, the researchers found that women who ate bread fortified with encapsulated iron were able to absorb the iron from the food.However, one drawback to this approach is that the polymer adds a lot of bulk to the material, limiting the amount of iron or other nutrients that end up in the food.“Encapsulating iron in polymers significantly improves its stability and reactivity, making it easier to add to food,” Jaklenec says. “But to be effective, it requires a substantial amount of polymer. That limits how much iron you can deliver in a typical serving, making it difficult to meet daily nutritional targets through fortified foods alone.”To overcome that challenge, Yang came up with a new idea: Instead of encapsulating iron in a polymer, they could use iron itself as a building block for a crystalline particle known as a metal-organic framework, or MOF (pronounced “moff”).MOFs consist of metal atoms joined by organic molecules called ligands to create a rigid, cage-like structure. Depending on the combination of metals and ligands chosen, they can be used for a wide variety of applications.“We thought maybe we could synthesize a metal-organic framework with food-grade ligands and food-grade micronutrients,” Yang says. “Metal-organic frameworks have very high porosity, so they can load a lot of cargo. That’s why we thought we could leverage this platform to make a new metal-organic framework that could be used in the food industry.”In this case, the researchers designed a MOF consisting of iron bound to a ligand called fumaric acid, which is often used as a food additive to enhance flavor or help preserve food.This structure prevents iron from reacting with polyphenols — compounds commonly found in foods such as whole grains and nuts, as well as coffee and tea. When iron does react with those compounds, it forms a metal polyphenol complex that cannot be absorbed by the body.The MOFs’ structure also allows them to remain stable until they reach an acidic environment, such as the stomach, where they break down and release their iron payload.Double-fortified saltsThe researchers also decided to include iodine in their MOF particle, which they call NuMOF. Iodized salt has been very successful at preventing iodine deficiency, and many efforts are now underway to create “double-fortified salts” that would also contain iron.Delivering these nutrients together has proven difficult because iron and iodine can react with each other, making each one less likely to be absorbed by the body. In this study, the MIT team showed that once they formed their iron-containing MOF particles, they could load them with iodine, in a way that the iron and iodine do not react with each other.In tests of the particles’ stability, the researchers found that the NuMOFs could withstand long-term storage, high heat and humidity, and boiling water.Throughout these tests, the particles maintained their structure. When the researchers then fed the particles to mice, they found that both iron and iodine became available in the bloodstream within several hours of the NuMOF consumption.The researchers are now working on launching a company that is developing coffee and other beverages fortified with iron and iodine. They also hope to continue working toward a double-fortified salt that could be consumed on its own or incorporated into staple food products.The research was partially supported by J-WAFS Fellowships for Water and Food Solutions.Other authors of the paper include Fangzheng Chen, Wenhao Gao, Zhiling Zheng, Tian Wang, Erika Yan Wang, Behnaz Eshaghi, and Sydney MacDonald. More

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      A new biodegradable material to replace certain microplastics

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      Microplastics are an environmental hazard found nearly everywhere on Earth, released by the breakdown of tires, clothing, and plastic packaging. Another significant source of microplastics is tiny beads that are added to some cleansers, cosmetics, and other beauty products.In an effort to cut off some of these microplastics at their source, MIT researchers have developed a class of biodegradable materials that could replace the plastic beads now used in beauty products. These polymers break down into harmless sugars and amino acids.“One way to mitigate the microplastics problem is to figure out how to clean up existing pollution. But it’s equally important to look ahead and focus on creating materials that won’t generate microplastics in the first place,” says Ana Jaklenec, a principal investigator at MIT’s Koch Institute for Integrative Cancer Research.These particles could also find other applications. In the new study, Jaklenec and her colleagues showed that the particles could be used to encapsulate nutrients such as vitamin A. Fortifying foods with encapsulated vitamin A and other nutrients could help some of the 2 billion people around the world who suffer from nutrient deficiencies.Jaklenec and Robert Langer, an MIT Institute Professor and member of the Koch Institute, are the senior authors of the paper, which appears today in Nature Chemical Engineering. The paper’s lead author is Linzixuan (Rhoda) Zhang, an MIT graduate student in chemical engineering.Biodegradable plasticsIn 2019, Jaklenec, Langer, and others reported a polymer material that they showed could be used to encapsulate vitamin A and other essential nutrients. They also found that people who consumed bread made from flour fortified with encapsulated iron showed increased iron levels.However, since then, the European Union has classified this polymer, known as BMC, as a microplastic and included it in a ban that went into effect in 2023. As a result, the Bill and Melinda Gates Foundation, which funded the original research, asked the MIT team if they could design an alternative that would be more environmentally friendly.The researchers, led by Zhang, turned to a type of polymer that Langer’s lab had previously developed, known as poly(beta-amino esters). These polymers, which have shown promise as vehicles for gene delivery and other medical applications, are biodegradable and break down into sugars and amino acids.By changing the composition of the material’s building blocks, researchers can tune properties such as hydrophobicity (ability to repel water), mechanical strength, and pH sensitivity. After creating five different candidate materials, the MIT team tested them and identified one that appeared to have the optimal composition for microplastic applications, including the ability to dissolve when exposed to acidic environments such as the stomach.The researchers showed that they could use these particles to encapsulate vitamin A, as well as vitamin D, vitamin E, vitamin C, zinc, and iron. Many of these nutrients are susceptible to heat and light degradation, but when encased in the particles, the researchers found that the nutrients could withstand exposure to boiling water for two hours.They also showed that even after being stored for six months at high temperature and high humidity, more than half of the encapsulated vitamins were undamaged.To demonstrate their potential for fortifying food, the researchers incorporated the particles into bouillon cubes, which are commonly consumed in many African countries. They found that when incorporated into bouillon, the nutrients remained intact after being boiled for two hours.“Bouillon is a staple ingredient in sub-Saharan Africa, and offers a significant opportunity to improve the nutritional status of many billions of people in those regions,” Jaklenec says.In this study, the researchers also tested the particles’ safety by exposing them to cultured human intestinal cells and measuring their effects on the cells. At the doses that would be used for food fortification, they found no damage to the cells.Better cleansingTo explore the particles’ ability to replace the microbeads that are often added to cleansers, the researchers mixed the particles with soap foam. This mixture, they found, could remove permanent marker and waterproof eyeliner from skin much more effectively than soap alone.Soap mixed with the new microplastic was also more effective than a cleanser that includes polyethylene microbeads, the researchers found. They also discovered that the new biodegradable particles did a better job of absorbing potentially toxic elements such as heavy metals.“We wanted to use this as a first step to demonstrate how it’s possible to develop a new class of materials, to expand from existing material categories, and then to apply it to different applications,” Zhang says.With a grant from Estée Lauder, the researchers are now working on further testing the microbeads as a cleanser and potentially other applications, and they plan to run a small human trial later this year. They are also gathering safety data that could be used to apply for GRAS (generally regarded as safe) classification from the U.S. Food and Drug Administration and are planning a clinical trial of foods fortified with the particles.The researchers hope their work could help to significantly reduce the amount of microplastic released into the environment from health and beauty products.“This is just one small part of the broader microplastics issue, but as a society we’re beginning to acknowledge the seriousness of the problem. This work offers a step forward in addressing it,” Jaklenec says. “Polymers are incredibly useful and essential in countless applications in our daily lives, but they come with downsides. This is an example of how we can reduce some of those negative aspects.”The research was funded by the Gates Foundation and the U.S. National Science Foundation. More

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      in Security

      Linzixuan (Rhoda) Zhang wins 2024 Collegiate Inventors Competition

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      Linzixuan (Rhoda) Zhang, a doctoral candidate in the MIT Department of Chemical Engineering, recently won the 2024 Collegiate Inventors Competition, medaling in both the Graduate and People’s Choice categories for developing materials to stabilize nutrients in food with the goal of improving global health.  The annual competition, organized by the National Inventors Hall of Fame and United States Patent and Trademark Office (USPTO), celebrates college and university student inventors. The finalists present their inventions to a panel of final-round judges composed of National Inventors Hall of Fame inductees and USPTO officials. No stranger to having her work in the limelight, Zhang is a three-time winner of the Koch Institute Image Awards in 2022, 2023, and 2024, as well as a 2022 fellow at the MIT Abdul Latif Jameel Water and Food Systems Lab.  “Rhoda is an exceptionally dedicated and creative student. Her well-deserved award recognizes the potential of her research on nutrient stabilization, which could have a significant impact on society,” says Ana Jaklenec, one of Zhang’s advisors and a principal investigator at MIT’s Koch Institute for Integrative Cancer Research. Zhang is also advised by David H. Koch (1962) Institute Professor Robert Langer. Frameworks for global healthIn a world where nearly 2 billion people suffer from micronutrient deficiencies, particularly iron, the urgency for effective solutions has never been greater. Iron deficiency is especially harmful for vulnerable populations such as children and pregnant women, since it can lead to weakened immune systems and developmental delays. The World Health Organization has highlighted food fortification as a cost-effective strategy, yet many current methods fall short. Iron and other nutrients can break down during processing or cooking, and synthetic additives often come with high costs and environmental drawbacks. Zhang, along with her teammate, Xin Yang, a postdoc associate at Koch Institute, set out to innovate new technologies for nutrient fortification that are effective, accessible, and sustainable, leading to the invention nutritional metal-organic frameworks (NuMOFs) and the subsequent launch of MOFe Coffee, the world’s first iron-fortified coffee. NuMOFs not only protect essential nutrients such as iron while in food for long periods of time, but also make them more easily absorbed and used once consumed.The inspiration for the coffee came from the success of iodized salt, which significantly reduced iodine deficiency worldwide. Because coffee and tea are associated with low iron absorption, iron fortification would directly address the challenge.However, replicating the success of iodized salt for iron fortification has been extremely challenging due to the micronutrient’s high reactivity and the instability of iron(II) salts. As researchers with backgrounds in material science, chemistry, and food technology, Zhang and Yang leveraged their expertise to develop a solution that could overcome these technical barriers. The fortified coffee serves as a practical example of how NuMOFs can help people increase their iron intake by engaging in a habit that’s already part of their daily routine, with significant potential benefits for women, who are disproportionately affected by iron deficiency. The team plans to expand the technology to incorporate additional nutrients to address a wider array of nutritional deficiencies and improve health equity globally.Fast-track to addressing global health improvementsLooking ahead, Zhang and Yang in the Jaklenec Group are focused on both product commercialization and ongoing research, refining MOFe Coffee to enhance nutrient stability and ensuring the product remains palatable while maximizing iron absorption.Winning the CIC competition means that Zhang, Yang, and the team can fast-track their patent application with the USPTO. The team hopes that their fast-tracked patent will allow them to attract more potential investors and partners, which is crucial for scaling their efforts. A quicker patent process also means that the team can bring the technology to market faster, helping improve global nutrition and health for those who need it most. “Our goal is to make a real difference in addressing micronutrient deficiencies around the world,” says Zhang.   More

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      in Security

      Study reveals the benefits and downside of fasting

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      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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      in Energy

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

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      “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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      in Security

      Exploring the links between diet and cancer

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      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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      in Energy

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

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      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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      in Environment

      Recycling plastics from research labs

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      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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      in Security

      Microparticles could help prevent vitamin A deficiency

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      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