70 influential creatives are set to take the stage.

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Jane Muschenetzs poems dont look like the sonnets you remember studying in high school English. If anything, theyre more likely to call to mind your statistics class.Flip through the pages of her poetry chapbook Power Point and youll see charts, graphs, and citations galore. One poem visually documents maternal mortality rates and womens unpaid domestic labor in such a way that the bar and pie graphs spell out the word MOM. Another tracks deaths from gun violence across the globe and is presented as a gun-shaped graph. Still others are written in more standard poetic form but include citations that reference documents put out by the US government, the United Nations, and news organizations.These poems are just a few of the many in Muschenetzs latest book that wrestle with contemporary social issues using a combination of data-driven insights and the poetic form. The format is a unique one: The first time Hayley Mitchell Haugen, founding editor in chief of Muschenetzs publisher Sheila-Na-Gig, saw the poems, she thought to herself, Ive never seen anything like this before.Point Blank13. Incidents of firearm mortality per 100K population for high income global economies with populations over 10M, Institute for Health Metrics Evaluation, United Nations. Graphics treatment by Ingo Muschenetz. 14. Child and Teen Firearm Mortality in the US and Peer Countries, per 100K population, KFF.org, July 2023; CDC. Detailed citations at technologyreview.com/Muschenetz.ORIGINALLY PUBLISHED BY WRITERS RESIST, WINTER 2023While cold, hard numbers and poetry might seem antithetical at first blush, from Muschenetzs perspective, the two couldnt be a better fit. A former business consultant at Bain & Company who received her MBA at the Sloan School of Management, she released her first poetry book in her 40s, and shes enjoyed uncovering what the artistic and scientific approaches to understanding the world have in common.Even though it maybe feels unintuitive that poetry and science are interrelated, they both make connections that are not immediately obvious, she says. They test out theories; they take risks. Theres a lot of nonlinear thinking that happens in both.Many of the poems in Power Point were inspired by watershed moments in global politics and culture, particularly ones that would shape the lives of women. From the partisan political theater on display at the confirmation hearing of US Supreme Court Justice Ketanji Brown Jackson to the passage of laws restricting womens freedoms in Iran and Afghanistan, these events often left Muschenetz overwhelmed with frustration at the state of womens rights today.But knowing that womens emotions are so often dismissed, she looked for a way to turn those feelings into something that she hoped would be harder to write off than standard poetry while still evoking the openheartedness with which people tend to approach art.I wanted something that listed just facts but expressed how angry I am, she says. I really wanted it to be fact-based. I wanted my sources to be publicly available and almost unassailable. Her hope was that by repackaging these facts in the form of statistics-driven poetry, she might allow readers to receive the information in a new wayand get them thinking.From Ukraine to CaliforniaMuschenetzs childhood primed her to understand how global currents can shape an individual life from an early age. Born Yevgenia Leonidovna Veitzman to a Jewish family in the Ukrainian city of Lviv, Muschenetz says her family began trying to leave the country before she was born, hoping to escape the discrimination they faced under the Soviet government. But it wasnt until she was 10 years old that the family was finally able to emigrate. When they were at last cleared to cross the border, they headed for San Diego, where she decided that Jane would be easier for Americans to pronounce than her given first name. (Ultimately, she would change her last name, too, when she married.)Muschenetz often felt out of place in her new home, even though she was surrounded by other immigrant kids whose parents had moved to California in search of a better life. In one way she was like many American teenage girls, though: She had a lot of feelings, especially about romantic relationships, whether real or imagined, and she often wrote poems about them. At age 16, she began submitting her poetry to magazines and publishers, which brought her first taste of writerly rejection. I was like, Oh, well, I tried. Clearly this isnt for me. Even though in my heart, since I was like four years old, I knew I was a writer and I loved literature, she says.Her parents were completely horrified about the prospect of her pursuing a career in writing, but they werent much more excited about what she eventually landed on instead: a degree in political science at UC San Diego. The response was always Poets get shot. Politicians get shot, she says.She might not have been able to articulate it at age 18, but looking back, Muschenetz makes sense of the decision to study political science as driven by her desire to understand the global forces that caused her family to emigrate. I wanted to know: How do we structure policy? Who makes these choices, and how can we change them and make them better? she says.STACY KECKBut the dream of writing was hard to let go of. By the time Muschenetz was a few years out of college, shed applied for two different programs: an MFA in writing and the MBA program at Sloan. And though she didnt get accepted to the MFA program, her time at Sloan ended up profoundly shaping the poetry she would write two decades later, giving her the statistical analysis and data interpretation skills that formed the backdrop for Power Point. Those were skills she sharpened even further in the years she spent working as a business consultant at Bain right after earning her MBA.I dont think the average joe could pull off [what she does in that book], because she knows how to present statistics well, says Haugen. She knows how to look at them analytically and offer them up in a way that a layperson can understand.Muschenetz left the business world after four years at Bain to focus on parenting her two children, as well as serving in various volunteer capacities at their schools and with local community organizations. It wasnt until the world shut down in 2020 with the onset of the covid-19 pandemic that she found herself getting back in touch with the creative impulses that had animated her previously. Those impulses manifested in part as visual art: Muschenetz began painting a menagerie of animals on the bases of palm fronds she would find on the ground after a big storm in San Diego. It just felt good, even though it made no sense, she says. At the same time, it was keeping me sane.Being willing to dip her toe into a creative endeavor that she knew she didnt have to be good at also helped open Muschenetz to the idea of getting back to the poetry writing that had made her heart sing as a girl.Through my high school and early college years, every margin of every notebook was covered with poems or rhymes, she says. And then it was just gone. It was scary for me to realize that I had cut that part out of myself, and how bad that was for me.Coming home to poetryWhen Muschenetz did start writing again, she thought she might write a collection of poems rooted in domesticity and home life. She was surprised to find that what started flowing out of her instead were poems about her immigrant experience, which had never been the subject of her poetry while she was living it as a teenager. I thought, Well, shouldnt I have gotten this out of my system? But here I was writing about this aspect of my identity that I never actually had written about before.She eventually had enough poems to pull together what became her first collection, titled All the Bad Girls Wear Russian Accents. The book reveals her propensity for weaving together dark and light, humor and tragedy, in a range of poems that cover everything from the war in Ukraine to the experience of being stereotyped for her ability to speak Russian, the language of many American movie villains.Muschenetz initially thought that writing a book of poetry might be a onetime thing, the kind of undertaking that would allow her to check a box and move on. But as she was promoting her first book, she found herself fixating on a poem she hadnt even written yetone in the form of data that would spell out a word. The idea was eventually realized in 100% MOM.100% MOM: A PowerPoint Poem about Women and LaborData sources include: Life Stages and Populations by Sex,CDC, NCHS; Most pregnancy-related deaths are preventable, Hear Her Campaign, CDC, 2022; The U.S. Maternal Mortality Crisis Continues to Worsen: An International Comparison, Commonwealth Fund, 2022; The Worlds Women 2020 Trends and Statistics, United Nations; Oxfam International Inequality Reports: 2020, 2021; Hard Work Is Not Enough: Women in Low-Paid Jobs, National Womens Law Center, July 2023. Detailed citations at technologyreview.com/Muschenetz.ORIGINALLY PUBLISHED IN WHALE ROAD REVIEW, SPRING 2023That poem was the seed that grew into Power Point, and Muschenetz, whose poetry has been nominated for the Pushcart Prize three times, hasnt looked back since. In addition to releasing that second volume of poetry, the product of what she calls the analytic and overachieving brain that helped her get through (and enjoy) business school, Muschenetz has used those same skills to help the poetry community in San Diego with some of the more practical needs, like grant writing, that are often lacking in communities of artists, says Katie Manning, a local poet and professor emeritus of poetry.Muschenetz is mostly just happy to have found a way to use poetry to keep integrating and honoring the many different parts of her identity, from immigrant to business consultant.It is a huge disservice to all humanity when we ask our scientists or mathematicians or poets to only be that one thing, as opposed to being their whole selves, she says.You Are 600% Hotter than the SunBy Jane MuschenetzA cup of the Suns core produces ~60 milliwattsof thermal energy. By volume less than that ofa human [350 mW]. In a sense, you are hotter thanthe Suntheres just not as much of you.Henry Reich, Minute PhysicsSpeaking roughly, in terms of heatgenerated per every human inch, you giveoff more milliwattssurge/energy. Onlythe Sun is bigger it matters.We are all blindedby love, the expanding/contractinguniverse is just another metaphorfor longing, and lifeits own purpose.How dazzling, this science!Consider falling for a physicistthe painstakingly slow way they undressmathematical mysteries,talk about bodies in motiongets me every timespacecontinuum, part, particleAtomic. Incandescent! Youare, pound-for-pound, more Life-Source,more Bomb, more Season-Spinning Searing CenterHeart/Engine/Radiating Nuclear Dynamicthan the Sun. Cant look directlyin the mirror? Small Wonder! Imaginenone of us powerless.Originally published by Cathexis Northwest Press, May 2024For Those of Us Forced to FleeBy Jane MuschenetzFor those of us forced to fleethe world is forever shrinking down to a single question:What can you carry?The suitcase of your heart closed tighton all the things there was no room to bringyour memories of home, the snowflake momentsof your youth, the blooming Lilac treeoutside your bedroom window a heavy burdensaps your strength on the long journey, bringonly what you need.Homes can be built again,a new tree can be rooted.Survive.When you have nothing left to plant, become the seed.Originally published in Issue 8, The Good Life Review, 2022. It received the 2022 Honeybee Poetry Prize and was nominated for a Pushcart Prize.Find more poetry by Jane Muschenetz at www.palmfrondzoo.com/janewriting.

Microbes that gobble up or break down environmental toxins can clean up oil spills, waste sites, and contaminated watersheds. But until his faculty mentor asked him for help with a project he was working on with doctors at Boston Childrens Hospital in 2009, Eric Alm had not thought much about their role in a very different environment: the human digestive system.David Schauer, a professor of biological engineering, was examining how microorganisms in the gut might be linked to inflammatory bowel disease (IBD), and he hoped advanced statistical analysis of the data he was collecting could make those connections clearer. Alm, whod joined the civil and environmental engineering faculty in 2006 as a computational biologist studying environmental uses of microbes, had the statistical experience needed and could apply machine-learning tools to help. But for him, the project was supposed to be a brief detour. In June of 2009, however, Schauerjust 48died unexpectedly, only two weeks after falling ill. Alm, heartbroken, worked to help push his mentors project over the finish line. As that effort was underway, Neil Rasmussen 76, SM 80, a longtime member of the MIT Corporation and the philanthropist funding the project, asked for a tour of his lab. That encounter would change the course of Alms career.At the end of the lab tour, Rasmussen, who has a family member with IBD, had a surprise: He asked Alm if hed be willing to pivot to researching inflammatory bowel diseaseand offered to fund his lab if he did so.Alm was game. He began shifting the main focus of his research away from harnessing microbes for the environment and turned most of his attention to exploring how they could be applied to human health. Then Rasmussen decided he wanted to do something really big, as Alm puts it, and make Boston a hub for microbiome research. So in 2014, with a $25 million grant from the Neil and Anna Rasmussen Foundation, the Center for Microbiome Informatics and Therapeutics (CMIT) was launched with Alm and Ramnik Xavier, chief of gastroenterology at Massachusetts General Hospital, as its co-directors.CMIT co-director Eric Alm is a professor of biological engineering and civil and environmental engineering and an Institute Member of the Broad Institute. His research uses data science, quantitative analysis, and novel molecular techniques toengineer the human microbiome.COURTESY OF ERIC ALMBy teaming up with Alm and others, Rasmussen hoped to create a research hub where scientists, engineers, doctors, and next-generation trainees would collaborate across scientific disciplines. They would build the tools needed to support a new research field and translate cutting-edge research into clinic-ready interventions for patients suffering from a wide range of inflammatory and autoimmune conditions influenced by the gut, including not only IBD but diabetes and Alzheimersand potentially autism, Parkinsons disease, and depression as well. In its first 10 years, CMIT has made remarkable progress.When the center started, Alm says, it was still a relatively novel idea that the human microbiomeparticularly the community of trillions of symbiotic microbes that reside in the gutmight play a key role in human health. Few serious research programs existed to study this idea. It was really this undiscovered territory, he recalls. [In] a lot of diseases where there seemed to be things that we couldnt explain, a lot of people thought maybe the microbiome plays a role either directly or indirectly. It has since become increasingly clear that the microbiome has a far greater impact on human health and development than previously thought. We now know that the human gutoften defined as the series of food-processing organs that make up the gastrointestinal tractis home to untold trillions of microorganisms, each one a living laboratory capable of ingesting nutrients, sugars, and organic materials, digesting them, and releasing various kinds of organic outputs. And the metabolic outputs of these gut-dwelling microbes are similar to those of the liver, Alm says. In fact, the gut microbiome can essentially mirror some of the livers functions, helping the body metabolize carbohydrates, proteins, and fats by breaking down complex compounds into simpler molecules it can process more easily. But the guts outputs can change in either helpful or harmful ways if different microbes establish themselves within it.I would love to have bacteria that live on my face and release sunscreen in response to light. Why cant I have that?Tami LiebermanOur exquisite immune defenses evolved in response to the microbiome and continue to adapt during our lifetime, Rasmussen says. I believe that advancing the basic science of human interactions with the microbiome is central to understanding and curing chronic immune-related diseases.By now, researchers affiliated with the center have published some 200 scientific papers, and it has found ways to advance microbiome research far beyond its walls. It funds a team at the Broad Institute (where Alm is now an Institute Member) that does assays and gene sequencing for scientists doing such research. Meanwhile, it has established one of the worlds most comprehensive microbiome strain libraries, facilitating studies around the globe.To create this librarywhich includes strains in both the Broad InstituteOpenBiome Microbiome Library and the Global Microbiome Conservancys Biobankresearchers have isolated more than 15,000 distinct strains of microbes that are found in the human gut. The library can serve as a reference for those hoping to gain information on microbes they have isolated on their own, but researchers can also use it if they need samples of specific strains to study. To supplement the strain library, CMIT-affiliated researchers have traveled to many corners of the globe to collect stool samples from far-flung indigenous populations, an effort that continues to this day through the Global Microbiome Conservancy. Were trying to build a critical mass and give folks working in different labs a central place where they can communicate and collaborate, says Alm. We also want to help them have access to doctors who might have samples they can use, or doctors who might have problems that need an engineering solution. The clinical applications produced by CMIT have already affected the lives of tens of thousands of patients. One of the most significant began making an impact even before the centers official launch.For decades, hospitals had been grappling with the deadly toll of bacterial infections caused by Clostridioides difficile (C. diff), a hardy, opportunistic bacterium that can colonize the gut of vulnerable patients, often after heavy doses of antibiotics wipe out beneficial microbes that usually keep C. diff at bay. The condition, which causes watery diarrhea, abdominal pain, fever, and nausea, can be resistant to conventional treatments. It kills roughly 30,000 Americans every year.By 2003, researchers had discovered that transplanting stool from a healthy donor into the colon of a sick patient could restore the healthy microbes and solve the problem. But even a decade later, there was no standardized treatment or protocolrelatives were often asked to bring in their own stool in ice cream containers. In 2013, Mark Smith, PhD 14, then a graduate student in Alms lab, cofounded the nonprofit OpenBiome, the nations first human stool bank. OpenBiome developed rigorous methods to screen donors (people joke that its harder to get approved than to get into MIT or Harvard) and standardized the procedures for sample processing and storage. Over the years, the nonprofit has worked with some 1,300 health-care facilities and research institutions and facilitated the treatment of more than 70,000 patientswork that OpenBiome says helped set the stage for the US Food and Drug Administration to approve the first microbiome-based therapeutic for recurrent C. diff infections. Today, CMITs flagship effort is a 100-patient clinical trial that it launched to study IBD, using a wide array of technologies to monitor two cohorts of patientsone in the US and the other in the Netherlandsover the course of a year. People with Crohns disease and ulcerative colitis typically experience periods of full or partial remission, but they currently have no way to predict when they will relapse. So researchers are tracking weekly changes in each patients microbiome and other biological indicators while amassing continuous physiological data from Fitbits and recording self-reported symptom scores along with other clinical data. The goal is to identify biomarkers and other indicators that might be used to predict flare-ups so that already approved therapies can be used more effectively.Although data is still being collected, early analysis suggests that a patients gut microbiome begins to change six to eight weeks before flare symptoms appear, and a few weeks later, genetic analysis of epithelial cells in their stool samples starts to show signs of increased inflammation. The team is planning to host a hackathon this summer to help speed analysis of the mountain of disparate types of data being collected. Meanwhile, the community of clinicians, engineers, and scientists CMIT has nurtured is undertaking projects that Alm could hardly have imagined when he first delved into research on the human microbiome.Survivor: Microbe editionRight below the photograph on the bio page of her Twitter/X account, Alyssa Haynes Mitchell has three emojis: a tiny laptop, a red and blue strand of DNA, and a smiling pile of poo. The digital hieroglyphics neatly sum up her area of focus as she pursues a doctorate in microbiology. A 2024 Neil and Anna Rasmussen fellow, Mitchell is attempting to understand precisely what it is that allows microbes to survive and thrive in the human gut.Mitchell fell in love with the study of microbes as an undergrad at Boston University. First, her mind was blown after she read a paper by researchers who could create a facsimile of a patients intestinal cell populationa gut on a chipand planned to culture a microbiome on it. She was fascinated by the idea that this might lead to personalized treatments for conditions like IBD. Then she cultured her first colony of a strain of the microbe Bacillus subtilis that had been genetically engineered to fluoresce.They form these really complex ridges, and the more you look at microscopy images, the more you realize that theres patterns of collective behavior of bacterial biofilms that we just dont understand, she says. Theyre super beautiful, and its really quite amazing to look at.In 2023, Mitchell joined the lab of Tami Lieberman, an associate professor of civil and environmental engineering and a member of both CMIT and MITs Institute for Medical Engineering and Science.Mitchell and others who study the microbiome think that probiotics, beneficial microbes that are applied to the skin or ingested in supplements or foods such as yogurt or kombucha, could have broad potential to help treat disease. But for reasons that still arent well understood, once probiotics are introduced into the gut, only a small percentage of them are able to survive and proliferate, a process known as engraftment. A probiotic with an engraftment rate of 30% (meaning its still detectable in 30% of subjects) six months after administration is considered good, says Mitchell. She and Lieberman, who also holds the title of Hermann L.F. von Helmholtz Professor, are studying the way individual strains of microbes evolve to survive in the microbiomea key mystery that needs to be solved to engineer more effective, longer-lasting therapies. Alyssa Haynes Mitchell, a PhD student pursuing a doctorate in microbiology, is working with Tami Lieberman, an assistant professor of civil and environmental engineering, to study how strains of microbes evolve to survive in the gut. Lieberman also studies how microbes survive and proliferate on the skin.Hopefully if we learn a little bit more about what drives evolution of the ones that stick around, we might be able to learn why some dont, she says.Mitchell has been working with samples collected by a local biotech company developing biotherapeutics for the gut. Its probiotic products, which are used to treat recurrent C. diff infections, contain eight closely related microbial strains belonging to the order known as Clostridiales. The company gave one of its products to 56 human subjects and collected stool samples over time. Mitchell is using genetic sequencing techniques to track how three of the microbial species evolved in 21 of the subjects. Identifying person-specific differences and similarities might reveal insights about the host environment and could help explain why some types of mutations allow some microbes to survive and thrive. The project is still in its early phases, but Mitchell has a working hypothesis.The model that I have in my mind is that people have different [gut] environments, and microbes are either compatible with them or not, she says. And theres a window in which, if youre a microbe, you might be able to stick around but maybe not thrive. And then evolution kind of gets you there. You might not be very fit when you land there, but youre close enough to hang around and get there. Whereas in other people, youre totally incompatible with whats already there, and the resident microbes beat you out.Her work is just one of many projects using new approaches developed by Lieberman, who worked as a postdoc in Alms lab before starting her own in 2018. As a graduate student at Harvard, Lieberman gained access to more than 100 frozen samples collected from the airways, blood, and chest tissue of 14 patients with cystic fibrosis, a genetic disease that causes mucus to build up in the lungs and creates conditions ripe for infections. The patients were among those who had developed bacterial infections during an outbreak in the 1990s. Lieberman and her colleagues recognized a perfect opportunity to use genetic sequencing technologies to study the way the genome of the Burkholderia dolosa bacterium evolved when she cultured those samples. What was it that allowed B. dolosa to adapt and survive? Many of the surviving microbes, she discovered, had developed similar mutations independently in different patients, suggesting that at least some of these mutations helped them to thrive. The research indicated which genes were worthy of further studyand suggested that this approach holds promise for understanding what it takes for microbes to grow well in the human body.Lieberman joined Alms lab in 2015, aiming to apply the same experimental paradigm and the statistical techniques she had developed to the emerging field of microbiome research. In her own lab, she has developed an approach to figuring out how the pressures of natural selection result in mutations that may help certain microbes to engraft. It involves studying colonies of bacteria that form on the human skin.The idea is to create a genetically engineered metabolite factory in the gut.Daniel PascalIn the gut, Lieberman explains, hundreds of different species of microbes coexist and coevolve, forming a heterogeneous community whose members interact with one another in ways that are not fully understood. This creates a wide array of confounding variables that make it more difficult to identify why some engraft and others dont. But on the skin, the metabolic environment is less complex, so fewer species of bacteria coexist. The smaller number of species makes it far easier to track the way the genomes of specific microbes change over time to facilitate survival, and the accessibility of the skin makes it easier to figure out how spatial structure and the presence of other microbes affect this process.One discovery from Liebermans lab is that each pore is dominated by just one random strain of a single species. Her group hypothesizes that survival may depend on the geometry of the pore and the location of the microbes. For example, as these anaerobic microbes typically thrive at the hard-to-access bottom of the pore, where there is less oxygen, the first to manage to get there can crowd out new migrants.My vision, and really a vision for the microbiome field in general, Lieberman says, is that one day therapeutic microbes could be added to the body to treat medical conditions. These could be microbes that are naturally occurring, or they could be genetically engineered microbes that have some property we want, she adds. But how to actually do that is really challenging because we dont understand the ecology of the system. Most bacteria introduced into a persons system, even those taken from another healthy human, will not persist in the new persons body, she notes, unless you first bomb it with antibiotics to get rid of most of the microbes that are already there. Why that is, she adds, is something we really dont understand.If Lieberman can solve the puzzle, the possible applications are tantalizing. I would love to have bacteria that live on my face and release sunscreen in response to light, she says. Why cant I have that? In the future, theres no reason we cant figure out how to do that in a safe and controlled manner. And it would be much more convenient than applying sunscreen every day.Harnessing light-sensitive, sunblock-producing microbes may sound like a distant fantasy. But its not beyond the realm of possibility. Other microbial products that sound straight out of a science fiction novel have already been invented in the lab.Molecular assassinWhen Daniel Pascal first landed in the lab of MIT synthetic biologist Christopher Voigt, he had no idea hed be staying on to make bacteria with superpowers. He was a first-year PhD student rotating through various labs, with little inkling of the potential contained in the microbes that live inside us.Pascal, a 2024 Neil and Anna Rasmussen fellow who is pursuing a doctorate in biological engineering, was originally paired with a graduate student doing a more materials-related synthetic biology project. But he came from a family of physicians and soon found himself speaking with other graduate students in the lab whose projects had to do with health.He then learned that two of the labs postdocs, Arash Farhadi and Brandon Fields, were receiving funding under a program sponsored by the Defense Advanced Research Projects Agency (DARPA), the Pentagons R&D organization, to develop solutions for common travelers ailments that result from problems like disrupted sleep cycles and limited access to safe food and water. When they explained that they hoped to harness microbes in the human body, they had his attention.Daniel Pascal, a graduate student pursuing a doctorate in biological engineering, is using synthetic biology to get microbes to carry out functions that they would not perform in the natural world.COURTESY OF DANIEL PASCALIts amazing how these tiny little organisms have so much control and can wreak so much havoc, he says. Intrigued, Pascal wound up officially joining Voigts lab, where he is working to create microbes that can carry out a wide array of functions they would not perform in the natural world. To do so, he is using a custom landing pad system developed in the lab. The system relies on synthetic biology to create a new region in the genome of a microbe that, using specific enzymes, can be filled with pieces of DNA designed to imbue the microbe with special new abilities. After engineering the landing pad into samples of an existing probiotic, Pascal and his collaborators on a project funded by the US Air Force and DARPA were able to deliver DNA that allows the probiotic to essentially set up a specialized drug production facility within the gut. First it absorbs two common amino acids, arginine and glycine. Then it converts them into a precursor compound that the body transforms into creatine, which can facilitate the production of muscle tissue from exercise and may help with memory. Pascal explains that creatine is often taken as an over-the-counter supplement by people doing weight training and other athletes who want to improve their fitness. But creatine has been shown to improve performance in fatigued humans, he says. So the motivation for this project was the idea that Air Force pilots that are traveling all over the world are jet-lagged, are working crazy hours and shifts. What if, the researchers wondered, those pilots could take a supplement that would improve some of their responsiveness, athletic accuracy, intelligence, and reasoning?A typical oral supplement delivers a spike of creatine in the bloodstream that largely dissipates relatively quickly. More useful to the pilots would be a probiotic engineered to produce a consistent amount of the creatine precursor that could be turned into creatine as needed.CMIT is also funding Pascals project using the landing pad system to get microbes to produce substances that target specific pathogens without disrupting the entire microbiome. Although Pascal cannot yet reveal any details about these molecular-level assassins, he notes that other researchers in the Voigt lab have recently used the landing pad system to redesign the Escherichia coli Nissle (EcN) microbe, which had previously been engineered to produce such things as antibiotics, enzymes that break down toxins, and chemotherapy drugs to fight cancer. The labs work made it possible to improve the efficacy of a treatment for phenylketonuria and perhaps of other EcN therapeutics as well. The lab has, in short, been able to get microbe strains (one of which he says is a commercially available probiotic that in some countries you can buy over the counter) to do some very useful things. Theyve figured out a way to take this mundane thing and give it these extraordinary capabilities, he says. The idea is to create a genetically engineered metabolite factory in the gut.Tackling childhood obesity Understanding the microbiome may also lead to new therapies for one of the greatest public health challenges currently facing the US: rising rates of obesity.Jason Zhang, a pediatric gastroenterologist at Boston Childrens Hospital, has received a CMIT clinical fellowship to study how gut bacteria may be linked to childhood obesity and diabetes. As a visiting scientist in Alms lab, he is using AI to predict peoples loss of control over what or how much they eat. His working hypothesis is that microbial metabolites are interacting with endocrine cells in the lining of the gut. Those endocrine cells in turn secrete hormones that travel to the brain and stimulate or suppress hunger.We believe that the microbiome plays a role in how we make choices around food, he says. The microbiome can send metabolites into the bloodstream that will maybe cross the blood-brain barrier. And there may be a direct connection. There is some evidence of that. But more likely theyre going to be interacting with cells in the epithelial layer in the gut.Jason Zhang, a pediatric gastroenterologist at Boston Childrens Hospital, studies the link between gut bacteria and childhood obesity and diabetes. As a visiting scientist in the lab of Eric Alm, he uses AI to model whats known as loss-of-control eating.COURTESY OF JASON ZHANGZhang has sequenced the microbes found in the stool of subjects who have exhibited loss-of-control eating and developed a machine-learning algorithm that can predict it in other patients on the basis of their stool samples. He and his colleagues have begun to home in on a specific microbe that appears to be deficient in kids who experience this eating pattern.The researchers have discovered that this particular microbe appears to respond to food in the gut by creating compounds that stimulate enteroendocrine cells to release a series of hormones signaling satiety to the brainamong them GLP-1, the hormone whose signal is turned up by weight-loss drugs like Ozempic. Zhang has already begun experimenting with therapies that artificially introduce the microbe into mice to treat obesity, diabetes, and food addiction. As with any single mechanism that treats a really complex disease, I would say its likely to make a difference, he says. But is it the silver bullet? Probably not. Still, Zhang isnt ruling it out: We dont know yet. Thats the ongoing work.All these projects provide a taste of whats to come. For more than a decade, CMIT has played a key role in building the fundamental infrastructure needed to develop the new field.But with as many as 100 trillion bacterial cells in the human microbiome, the efforts to explore it have only just begun.