Seth Bordenstein came to Penn State because he was impressed by the work being done, and by the potential to do so much more. Bordenstein, a biologist and entomologist who holds the J. Lloyd & Dorothy Foehr Huck Endowed Chair of Microbiome Sciences, was hired in 2022 as director of the One Health Microbiome Center, the massive, cross-disciplinary center within the Huck Institutes of the Life Sciences. The center combines two related areas of study that, outside of Penn State, hadn’t been unified under one roof: “one health,” which the CDC defines as “a collaborative, multisectoral, and transdisciplinary approach to achieving optimal health outcomes” that accounts for the interconnection between people, animals, plants, and their shared environment; and the microbiome, the collection of all microorganisms that naturally live in a particular environment. We spoke with Bordenstein about what that work entails, some of the center’s most promising research, and the factors that convinced him Penn State has “the best microbiome center in the world.”

PENN STATER: I want to start with the name of center, which I assume is intentionally broad given the scope of the work, and something I’m guessing you find yourself explaining a lot. How do you sum up the overall mission and work of the center?

SETH BORDENSTEIN: I love that you contextualized it—that’s exactly what we’re shooting for here. Really, it’s the big tent that we’re housing all microbiome scientists under. Our core mission is to un-silo the microbiome sciences; that means taking plant biologists, animal biologists, environmental biologists, soil biologists, and bringing them all into one tent. We actually underwent a strategic assessment of how we would rename our center when I got here two and a half years ago, and we spent nine months talking about what that term was going to be. And we ended up with One Health Microbiome Center, because “one health” encompasses the fact that the health of one ecosystem is dependent upon the health of another ecosystem. That’s it in a nutshell. In other words, environmental health is going to influence human health, agricultural health will influence environmental health and human health, and really, what meets in the middle is that aspirational aspect of research for us, which is, how can environmental and agricultural biologists work with human biologists to understand the flow of microbes through ecosystems, and how they shape the risks to health and disease.

PS: What was the center called before this?

BORDENSTEIN: Just the Microbiome Center, and it was one of 80 microbiome centers in the world. I thought we should name ourselves to brand and stand out. And in so doing, we have a mission to improve reputation and improve resources. And part of the way we’re improving our reputation is to say, “We’re not one of the 80, we are the only one health microbiome center in the world.” A lot of folks have followed up and told us they were going to try to take that name before we did, and we got to it first. It’s clear that there’s an emerging set of two areas: One is the rise of the microbiome sciences in the last decade or two, and the rise of one health in the last two decades. There are 80 centers in the world for microbiomes, and there’s about 100 one health academic units across the world; what we decided to do is merge them into the only One Health Microbiome Center, and that’s an intersection with intentionality, to bridge two emerging life science areas.

PS: You came to Penn State in 2022, after leading a similar center at Vanderbilt—was the chance to lead the microbiome center the primary draw? If so, can you expand on why?

BORDENSTEIN: I had led a microbiome center at Vanderbilt; I had moved it from a small boutique shop to a center, but it actually remained a boutique shop. It was sort of my lab and five other labs. I was attracted to Penn State because, instead of a boutique shop, it has a behemoth of a microbiome center. There’s 125 faculty, 550 members, and this was truly the playground that could be exemplary of the kind of center I would have liked to build at another place, and instead, we could enhance and build on it here. I became convinced it was the best microbiome center in the world through my interview process, and decided to join, and I have never been disappointed. It’s only been validatory that this is the best place for the microbiome sciences.

PS: Can you expand a bit on that? What makes it the best of its kind in the world?

BORDENSTEIN: What Penn State had done in the last decade was recruit and establish infrastructure for a very large microbiome center. And that was done by my predecessor, the previous director (Carolee Bull, professor of bacterial systematics and plant pathology). She had overseen recruitment of a lot of new faculty, as well as the establishment of an executive committee. What drew me to the One Health Microbiome Center was its depth of scale, its energy from young scientists on up, and its value to the world that hadn’t been appreciated in its fullest context. I thought that I could help unify the pieces that were there, add new components to it, and tell the world that this is one of the best places to do microbiome science, because the world hadn’t heard about it yet. I hadn’t heard about it yet; in fact, my interviews took me through the course of learning about the center. I knew it was there, but I didn’t know how special it was. As soon as I left my first and second interviews, it was clear that there was a large gravity pulling us to a place that I wanted to build myself, that was already being built at Penn State.

There was a simple design from my calculation about how to grow this center, a two-component design. It was, build your reputation, which will drive resources, which in turn will drive reputation—they start circling in a feedback loop. And it was clear the reputation had not been appreciated on the outside, and there was actually room to improve the reputation inside, because part of the leadership execution and strategy that we started to implement was to make sure everybody in the center knew that this was one of the best places to do microbiome science. I thought once people believed it inside, and once people heard it on the outside, there was no stopping the reality of this very large enterprise.

PS: The center was recently announced as the winner of the WH Pierce Global Impact in Microbiology Prize. Can you talk a bit about the significance of that, and how that aligns with building the center’s reputation?

BORDENSTEIN: At its simplest level, this award is bestowed by an international society called the Applied Microbiology International Group. So it’s an international award—that’s why it was important. The second thing was, there’s a prize culture in science that recognizes individuals over the collective, and it’s kind of an absurdity, because science is built off of collective effort. I was so proud of what the center had accomplished in its decade or more history that I thought this was a real chance to endorse an organization that truly earned the right to be awarded. We drafted a 10- page endorsement letter from the center that was signed by President [Neeli] Bendapudi and Senior Vice President [Andrew] Read, and in so doing, Applied Microbiology International recognized the endorsement of how good the center was. And it’s also, importantly, the first time in the 30-year history of the prize that a center or an organization has been awarded, rather than one or two individuals. I think we can be standard bearers not only for the science and education of the center through this international recognition, but also standard bearers for prize culture.

PS: Penn State has long had a reputation for supporting and valuing interdisciplinary collaboration, and the center seems to exemplify that—you’ve got more than 500 members, including hundreds of faculty and grad students, representing 10 Penn State colleges.

BORDENSTEIN: And multiple campuses, from Hershey to Altoona to University Park.

PS: Right, and I appreciate how significant that is. With that in mind, what are the biggest opportunities in that, and also the biggest challenges?

BORDENSTEIN: The biggest opportunity is the depth of scale, and the energy that comes from a large enterprise. We don’t necessarily have to build to be great; we just have to tap into leadership, execution, and momentum. And that truly is our mission, to define what a great microbiome center for the 21st century will be, and then be it. And fortunately, in our depth of scale, we didn’t really have to do much building, because it happened prior to me, and also it just comes from the fact that it’s a big university. So we’re going to dovetail with a lot. The other opportunity is, and this is really important: the cohort of assistant professor faculty who were here before me, who are growing in their impact and their energy of their science and education, is an essential interdisciplinary ingredient to why we’re successful. Because they’re not stretched too far as senior professors, they are building their research programs, and they’re building it with intent to be collaborative as part of the fabric of Penn State, but then as part of the fabric of the center, which many of these young faculty view as their first home, rather than their departments. Because we’re the glue that brings individuals from departments together—there isn’t a department of microbiome science—that young, assistant professor energy and opportunity at a large university really is part of the magic of why I think we’ve been so successful.

The challenges … I personally am not one who sees challenges. I really only see opportunities or solutions, so I have a difficult time answering those kinds of questions. The challenges for me really were maybe personally adapting from running a really small center at my previous institution to a very large one. In the first six months, my head was spinning around on my neck, but after that, I adapted, and I think I excelled at all the things that were going on. This is the best job I’ve ever had, so it really is hard to find those challenges, because opportunities abound.

PS: The membership of the center includes faculty, staff, post-docs—is there space for undergraduate research in this work?

BORDENSTEIN: In every lab that’s active in the microbiome sciences, there are very likely undergraduates doing research, for credit, for volunteership, including in my own lab. We also have an undergraduate microbiology club, so that’s part of the focus. I think in the future, our center is discussing what the future of undergraduate education might look like from a microbiome sciences perspective. For example, could there be a bachelor’s of science degree in microbiome sciences? Because we already have the first Ph.D. degree in the world in microbiome sciences. No other place is accredited to offer that. So as part of our leadership in that area, we’re also thinking about what a bachelor’s of science would look like. In theory, it’s also possible to have an interdisciplinary department of microbiome sciences, but that would require much more structural rearrangement of the life sciences—not something that I think is easy to chew on in your first couple of years. And not something that is maybe necessary either.

PS: What would a bachelor’s degree in microbiome sciences look like?

BORDENSTEIN: It could be an interdisciplinary program, actually. The Eberly College of Science does have an opportunity to do interdisciplinary, kind of make-your-own degrees, and with a little bit of oversight from us, I think we could orchestrate a microbiome sciences degree that’s independent of the departments, and in that sense we really could truly have interdisciplinary education going on for a science that is by definition interdisciplinary. It’s really hard to define—are we ecology? Are we genomics? Are we microbiology? We’re all of the above.

PS: The make-your-own nature of it—could that theoretically encompass pretty much any aspect of the work being done under this umbrella? I know there’s even an art component to the microbiome center.

BORDENSTEIN: I think so. In fact, we do have undergraduate artists working inside the labs of microbiome scientists to help them create cover art, or figures for papers. So there are opportunities for that, for sure.

I want to kind of give an overview of where this field is. The telescope is something humans use to look up and wonder about the world; we see stars and planets, and we wonder is life out there? But the microscope for us does the same thing, and it’s often overlooked, underneath our perception. And what we’re trying to do is really illuminate this enchantment about the microbial world through the microscope as much as we do through the telescope. And all of our biologists and beyond in this center are in fact feeling that; and part of our delivery back to the state, the nation, and the world is to make them as enchanted about the microbes as we are. And most of the microbes are helpful, not harmful, and that’s also part of our education.

PS: I’m guessing it’s a tough question to narrow down, but I wonder if you can highlight a few specific areas of research currently ongoing within the center that are particularly exciting?

BORDENSTEIN: I can answer that in broad strokes, and they all relate to what I call microbiome transplant therapy. Many people have heard of fecal microbiome transplants for things like C. difficile infections, and the idea is to restore good bacteria, good microbes, to an anatomical site that might be unhealthy or sick. In our human health range of the one health system, we have scientists doing oral microbiome transplant therapy research, as well as gut microbiome transplant therapy research for infections in both sites. In agricultural health, we have scientists working on microbiome transplant therapies for mushrooms, for wheat, for corn, for livestock. And in environmental health, we have scientists working on microbiome transplant research for protecting endangered species that are threatened by infectious diseases. One example of that is amphibians are experiencing some of the worst declines in animal biodiversity right now, they’re suffering from what’s called the chytrid fungus, and several of our scientists are working to understand how microbes naturally on the skin of these amphibians can protect them against this. So, transplant therapy across human, ag, and environmental health is what I’m most excited about for translating basic science into applied science that benefits humanity.

PS: Some of the collaborations really reach far beyond the hard sciences. Are there one or two that stick out for you, as far as how surprised folks might be that it falls under the microbiome center?

BORDENSTEIN: Well, for me it’s not a surprise, so I might have to take myself out of it. It sounds like the art is catching you—the art comes from this idea of fascination about looking down. Instead of looking up, we’re looking down. And we do have an executive committee member on the One Health Microbiome Center leadership; her name is Cynthia White, and she works in the Arts & Design Research Incubator, and she has facilitated multiple events of sci-art symposia, sci-art discussion groups, sci-art features in hallways and rooms around campus. And I really look to her for what else we can do. And one of our big visions is to create microbe museum features or art in the living campus. So, a student walks by a garden, we would have a display about how the microbes are helping that garden. When a student walks into a building, we would have a display about how microbes are flowing through the inside and shaping indoor health and their flow through those vent systems. I’d love to open people’s eyes in a sort of massive sci-art living campus approach. I think we’re serious about seeing if that’s a possibility in the future.

PS: President Bendapudi recently visited the center, and afterward, she said she was struck by how microbe science is “fundamental” to the university’s land-grant mission. Can you talk a bit about how the idea informs the work being done there?

BORDENSTEIN: The land-grant mission is obviously to give back to the community around you and beyond. It’s right in the fabric of our university, the land-grant mission. And we like to think about that through the lens of the microbes—that we are, quote-unquote, enhancing life from the microbes on up. Now, what does that mean? Well, that must mean that we’re doing research that has local and translational impact, which we are particularly strong in agricultural microbiome sciences. We have folks studying crops and livestock, and how microbes can make better output for the state of Pennsylvania and for the world. We also are interested in human health, and I mentioned the oral microbiome transplant and gut microbiome transplant research going on; another aspect of that is thinking about how microbiomes might vary between rural populations and city populations, and Pennsylvania is particularly well-suited for those kinds of studies, and we have them going on here as well. So, in effect, we could actually offer advice about dietary nutrition that optimizes microbiomes for either geographic area. Finally, I would say education is part of our mission, and we are doing a lot for science and outreach, to bring the science of the microbiome to local high schools and introductory college classrooms around the state and the world, and they can do biotechnology that allows them to discover microbes in their local fauna and flora. In fact, this program is active across the state already, and we’re working with the department of education to broaden it, and it’s much bigger than that. We work in 44 states and 20 countries to bring this biotechnology discovery series for microbes to high school students. They’re also learning biotech skills that prepare them for coming into the life sciences as an undergraduate, and we also hope that these programs will attract the best students to Penn State, because they’re learning about microbes and Penn State through this series that we offer.

PS: Who runs the educational outreach component?

BORDENSTEIN: My partner and wife, Sarah Bordenstein, directs it. It’s called “Discover the Microbes Within.” It’s all online at The Wolbachia Project, and it’s the major flagship science education part of our center. We brought it with us from Vanderbilt, we’ve been working on it for 15 years. We view Penn State and its campus network as a huge opportunity to tap into a large undergraduate population. She works with the Pennsylvania Department of Education, and with a number of faculty who are interested in bringing the research to the community.

Read more about how The Wolbachia Project provides students with real-world research opportunities.

PS: What’s on the horizon for the center? Are there specific areas of expansion or growth that are particular priorities?

BORDENSTEIN: I can think of resources, and I can think of financial opportunity. Let’s start with resources. We would like to have what’s called a biorepository for microbes, or what you could call the One Health Microbiome Ark. Which is to collect, store, and preserve microbes in a freezer bank so that if and when we need to resuscitate microbes for making health better, we have the largest repository, or largest biobank of microbes to do so. In fact, we already do. We’ve estimated the number of microbes that are stored at Penn State, and we’re at about 100,000 microbial strains or species stored at Penn State, which would make us one of the largest repositories. But we haven’t formalized it, and every lab is maintaining their microbes separately. So we’d like to unify an infrastructure with freezers and staff that would support it. The second would be that we’d like to establish what we call a One Health Microbiome Observatory with a long-term research field encompassing animals, plants, humans, soil, etc. We’d like to have, essentially, a high-resolution view of how microbes flow through that particular field site. Maybe it’s in The Arboretum, maybe it’s at a field site owned by Penn State, for example.

We have a couple other ideas, and a final, clear mission for us would also be that we’d like to have the center endowed in the short term. There are two endowed centers in the country, at Stanford and UCLA, and I think we’ve got a better center, frankly. I’d like us to be the third endowed center in the microbiome sciences, because I think we’re the best.

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