Decoding the Double Helix Treating disease, improving food and advancing science SUMMER 2022
145 Reef Relief Probiotics for coral Summer 2022, Vol. 27, No. 2 Scan this code with your camera to: • Get more content for each story • View back issues 8 30207 Family Medicine A father’s illness inspires UF geneticist 12 Innovation is in His DNA Thomas Burris takes the reins at the UF Genetics Institute Turtle Tracks eDNA leads the way Byte Test Can artificial intelligence bring tastier produce to our tables? No Time to be Patient Grad student knows disease first hand Revealing the Ancestry ‘Blind Spot’ Genetic ancestry shapes health disparities, but most biomedical experiments ignore it 26 Jaws of Life What sharks can teach us about regrowing teeth
Kent Fuchs President David Norton Vice President for Research Board of Trustees Mori Hosseini, Chair David L. Brandon Richard P. ExploreAnitaFredMarshaAmandaRahulDanielLaurenThomasJamesChristopherColeT.CorrW.HeavenerG.KuntzLemastersT.O’KeefePatelJ.PhalinD.PowersS.RidleyG.Zuckerispublished by UF Research. Opinions expressed do not reflect the official views of the university. Use of trade names implies no endorsement by the University of Florida. © 2022 University of Florida. Editor:explore.research.ufl.edu Joseph M. joekays@ufl.eduKays Art Director: Katherine Kinsley-Momberger Design and Illustration: Katherine Kinsley-Momberger Ivan J. Ramos Writers: Alisson Clark Natalie Van Hoose Photography: John Jernigan Tyler BrianneJonesLehan Web Editor: Ivan Ramos Social Media: Phillip Frohm Copy Editor: Bruce Mastron Printing: RR Donnelly, Orlando Member of the University Research Magazine www.urma.orgAssociation
s a young researcher, I can remember toiling away in a windowless lab, so focused on my work that I often did not even realize day had turned to night. For scientists, it is sometimes easy to get captivated by the microscopic world, so consumed by the details that we miss the potential broader impacts our research might have.
While there is much satisfaction to be gained when a disciplined focus on a narrow question yields a new insight, the most innovative and impactful research ers are able to go beyond, to harness the ability not only to unravel the small, but to simultaneously apply that insight to the broader world.
The University of Florida has a long history in genetics research, developing some of the earliest tools for inserting corrective genes into the human body. Today, our scientists are using those tools and others to change lives through genetics.
We learn how agricultural researchers are applying artificial intelligence to the genetics of taste to develop better fruits and vegetables.
A
4 S ummer 20224 S ummer 2022
Perhaps nowhere is this more true than in the nanoscale world of genetics, where segments of DNA provide the instructions for building molecules that impact every aspect of life. In this issue of Explore, we feature just a few of the hundreds of UF researchers who are harnessing the power of DNA to change theWeworld.meet the new director of the UF Genetics Institute, whose career in indus try and academia makes him uniquely qualified to promote UF’s basic research in genetics while also exploring how those discoveries can be translated to people who need them. We follow a diverse team of scientists and engineers looking at the relationship between biomedical research and human ancestry, recognizing the limitations of studies that do not take into account the diverse genetic ancestry of the people who should be reaping the benefits of science and technology.
BigMolecules,SmallImpact
And we introduce you to some remarkable genetics researchers whose personal experiences with disease motivates them to seek cures for others.
David Norton, Vice President for Research
homas Burris boarded his flight, found his seat and opened a book on nuclear receptors, the class of proteins he studies as a pharmacologist and molecular biologist. His seatmate glanced at the book title and shook his head in disapproval.
As director of UF’s Genetics Institute, Burris doesn’t have to explain that the nuclear receptors in our cells have nothing to do with nuclear reactors. But he does have to bridge the distance between disparate fields to foster the kind of innovation that’s possible when far-flung disci plines collide. It’s an approach he honed while launching pharmaceutical startups throughout his career, which has taken him from Ely Lilly to UF Scripps Biomedical Research (then Scripps Research Institute), and to St. Louis University and Washington University before taking on his role at UF in 2021.
“You're used to being able to describe how your science is going to affect human health, because in a company, if The Genetics Institute director on his startup mindset, leading by influence and sparking collaboration through polar bears
Innovation is in his DNA
Part of what drew him here was a long history of tech transfer. In May, the nonprofit Heartland Forward ranked UF first among public universities and second nationwide at moving discoveries from the lab to the world.
Thomas Burris
“I don’t approve of that stuff,” the man said. “Nuclear power is really bad.”
B y A liSSon C l Ark T
Industry experience helps Burris stay focused on the patient at the end of the pipeline.
“I've started four companies, and they can be quite chal lenging if the university is still in the early stages of the learning curve,” he says. “I felt confident that, given UF’s history, I could continue to do that here.”
JerniganJohn e xplore 5
His goals for the Genetics Institute include:
Thomas Burris Director, UF Genetics Institute Professor, College of burris.thomas@ufl.eduPharmacy
“It diversifies your thought process. Suddenly you’re talking to someone that you'd have never interacted with otherwise. Even though I may never work on that, maybe this person uses a technique that I can apply to what I'm doing.”Thomas Burris
In his role at UF, leading an institute of more than 200 researchers from eight colleges, he knows he’ll need to draw on a different toolbox than that of a department chair.
“Dr. Burris has broad interests overlapping multiple dis ciplines in genetics and genomics, and UF has a history of doing genetics research across disciplines,” says David Norton, UF’s vice president for research. “He brings a perspective that sets up the Genetics Institute to be even more successful.”
Since returning to academia in 2008, he has garnered more than $25 million in research funding. The move gave him license to delve deeper into nuclear receptors proteins that detect hormones and regulate gene expression laying groundwork that could lead to treatments for conditions from metabolic disease and Alzheimer’s to fatty liver disease and traumatic brain injury.
• Expanding master’s programs and adding certificate programs to build the pharmaceutical and biotechnology workforce, with a focus on AI integration in genomics.
6 S ummer 2022 you're not doing that, they don't want you,” he says. “I think that put me at an advantage in academia, where you have to explain your science to funders and reviewers.”
Burris also believes in opportunities for collision between disciplines, such as the UFGI Seminar Series, where he recently found himself learning about polar bear genetics.
• Pursuing NIH training grants to support Ph.D. stu dents, further developing a top-tier doctoral program for the biological sciences.
• Developing an NIH-funded Center of Excellence in Genomic Science with UFGI as the hub.
“Instead of line management, it’s more about administra tion by influence,” he says. “Everybody's following their own path, but a lot of their paths intersect. The chance of success increases the more those paths cross.”
• Increasing the use of chemical genomics technologies developed for drug discovery in other applications, from insect control to plant molecular biology.
• Leveraging relationships with researchers at UF Scripps Biomedical Research, one of the top National Institutes of Health-supported research centers in the state, which joined the research arm of UF’s academic health center this year.
As a bright student in a blue-collar Illinois town across the river from St. Louis, Burris initially thought he’d be a physician. In college, he quickly realized he preferred the lab to the bedside. He wound up at medical school anyway f irst as chair of the pharmacology and physiology department at Saint Louis University School of Medicine, then as a professor in the Washington University School of Medicine and St. Louis College of Pharmacy, where he also served as vice president for research.
“It diversifies your thought process,” he says. “Suddenly you’re talking to someone that you'd have never interacted with otherwise. Even though I may never work on that, maybe this person uses a technique that I can apply to what I'mThat’sdoing.”the potential inherent in the institute’s diverse fields, he says. “I want us to be known as a place where people from different areas want to come and interact,” he says. “When we suddenly bring a new light to a particular field, that's exciting.”
After sequencing the genomes of potential pro biotic strains and identifying how they work, the team will track how the strains colonize and alter the microbiome. UF leads the genetic sequencing com ponent, while the Smithsonian Marine Station and Nova Southeastern University will test the treatments in the “Wefield.want to know everything about the genome of the bacteria we're applying so we know all of its potential good, bad or in between,” she says.
“Bacteria are everywhere,” she says. “If we har ness their potential, we can alter the course of this disease.”Astatewide team is developing probiotic pastes made from the microbiome of healthy corals. When smeared on affected coral, the treatment should fight the disease by making its own antibiotics.
The work is supported by the Florida Department of Environmental Protection and Revive & Restore, an organization that leverages genetics and genomics in conservation.“Bacteriacan do any chemical reaction you can think of,” Meyer says. “If there's something you want to achieve, there's bacteria out there that can do it. We can find the solution if we just keep looking.”
Alisson Clark
Assistant Professor of Soil, Water, and Ecosystem Sciences juliemeyer@ufl.edu
Julie Meyer
You’ve probably heard of probiotics’ role in creat ing a healthy gut biome. But what if they could help coral reefs, too?
e xplore 7
By untangling the genetics of bacteria living around corals, she’s working to protect reefs from stony coral tissue loss, which attacks more than 20 coral species — imperiling tourism, fisheries and the storm surge protection reefs provide. Though the disease has swept through massive tracts of coral in just 7 years, Meyer, seen here collecting microbiome samples in the Cayman Islands , feels hopeful about the power of probiotics.
Microbial ecologist Julie Meyer and her collabora tors want to put beneficial bacteria to work fighting a coral disease that has spread around Florida and now reached the Caribbean.
“Instead of us going out and applying antibiot ics, which would be really expensive, it's a one-time application, with the idea that if these probiotic bacteria get established, they can continue to make antibiotics as needed,” Meyer says.
Reef Relief
8 S ummer 2022 JerniganJohn Eric Wang
A geneticist takes on a disease affecting millions including his father
“It's not common for a talented young person to declare a serious intent to work on myotonic dystrophy,” says Charles Thornton, a neurologist at the University of Rochester who received the email. “In the case of Eric Wang, I am very grate ful that he decided to go in this direction.”
Wang was 8 when his father was diagnosed with the disease, which intensifies over generations, robbing mobility, heart and cognitive function, and energy. Some of his relatives are unaffected or have few symptoms, while others have died. After finishing his degree in biochemistry, Wang was about to go to medical school when he started think ing there might be a better way to help. He knew his dad was running out of time
n 2006, specialists around the country started get ting emails from a recent Harvard grad named Eric Wang asking about myotonic dystrophy, an inher ited disease that runs in his family.
e xplore 9 SPECIAL ADVERTISING REPORT
Wang had one question: What do you need to know to find a cure?His plan: devote his career to filling in the gaps, developing treatments for his dad and millions of others worldwide.
It wasn’t unusual for them to hear from loved ones of patients hoping for a breakthrough, but this was different.
Family Medicine I
By Alisson C l Ark
“There's nowhere else in the world that has this concentration of basic scientists and clinical researchers working on this class of diseases.”EricWang
10 S ummer 2022
JerniganJohn
Like Huntington's disease and some types of ALS, myotonic dystrophy is a repeat expansion disorder, where extra copies of a genetic sequence in the protein-coding gene DMPK interfere with RNA processing, confusing or interrupting the instructions cells and tissues receive. Thornton and other experts who replied identified the same opportunities: Scientists needed to change their one-gene-at-a-time approach to encompass the whole genome and leverage high-throughput
“How do different molecules recog nize their vehicles? How do they know what bus to get on? What’s the code that underlies it? The process is impor tant to understand,” he says.
In Wang’s lab, students don’t have to choose between translational and fundamental science, says second-year graduate student Juan Arboleda, who joined as a technician in 2017. “What’s inspiring to me is that everyone contributes to the transla tional work,” Arboleda says. “It’s cool to see the basic science coming into play for therapeutic projects. You’d never be able to repair a plane unless you first know how it all works.”
In 2018, help arrived in the form of a $2.5 million award from the Chan Zuckerberg Initiative. The unrestricted funding designed to pursue ideas that might be deemed too audacious for other agencies — allowed him to build and staff a lab that doesn’t have to choose between unraveling the basic science behind the disease and developing therapies for it. His team of 20 now tackles both simultaneously. Some lab mem bers focus on gene therapy, others study how repeat expansions cause symptoms, or on the details of how thousands of mRNA and hundreds of RNA binding proteins travel through the body, which Wang likens to pas sengers getting on a bus.
It can be frustrating studying avia tion, though, when what you really want to do is board a flight. Wang feels the tension between time spent on basic science and therapeutics, especially when he talks to his father, who now uses a wheelchair and a pacemaker and battles brain fog and fatigue. His dad has a doctorate in physics, and the two always bonded over their love of scientific discovery. Now, “even my ability to communicate with him in the same way that I used to has changed,” Wang says. He knows therapeutics hinge on the basic science. And he knows his relatives and many others are counting on him allocating his hours the right way. He takes comfort in the strides he’s made toward addressing the deficits he asked about 16 years ago.
Eric Wang Associate Professor of Molecular Genetics & eric.t.wang@ufl.eduMicrobiology
“We’re much closer, but there’s still so much we don’t know,” Wang says. “We need more people working on this to change the landscape.”
The eager student who sent those emails to top scientists in 2006 now collaborates with them, “and likely will be the leading American researcher working on myotonic dystrophy,” says Thornton, the University of Rochester neurologist.“Ourfield would be a very different place if Eric was not in it. One person can make a huge difference, and he certainly has.”
“That gap has been filled,” he says. “The genome-wide approach happened, and not just in myotonic dystrophy. Taking things from a onegene, one-pathway approach to the genome-wide approach has been one of our major Discoveriescontributions.”fromhislab have been licensed to biotech companies and used in clinical trials. And advances in deep sequencing are helping identify how the disease disrupts gene expres sion and RNA processing: A micro wave-size machine in his lab can run 3 billion sequences overnight, which would have been unimaginable when he started this work.
e xplore 11 SPECIAL ADVERTISING REPORT sequencing to tease out the workings of different types of RNA. Wang took their advice to heart, dropping the med school plan and instead studying bioinformatics and integrative genomics at the HarvardMIT Division of Health Sciences and Technology. An NIH Director’s Early Independence Award allowed him to skip a postdoc and launch his lab at MIT. In 2015, he joined UF’s Center for “There'sNeurogenetics.nowhere else in the world that has this concentration of basic scientists and clinical researchers working on this class of diseases,” he says. “There’s a whole ecosystem here you can’t just build right away, with clinical trials, the McKnight Brain Institute, the Genetics Institute, the Myology Institute we have all the pieces in place.” Still, he feels the clock ticking. “When I was in grad school, I thought, ‘We're definitely going to have approved drugs soon.’ I'm 40 now. I'm close to halfway through my life,” he says. “What keeps me up at night is making the right decisions about how to spend my time, because time is the most limiting reagent.”
JerniganJohn
By Alisson Cl Ark No Time To be PaTieNT
She’d been having trouble with movement and balance since she was 9. Three years later, her doctors diagnosed her with Friedreich’s ataxia (FA). Knowing it was untreatable, incurable, and likely fatal, her parents didn’t tell her right away. Why burden her with knowing there was no hope?
As she persisted through her studies, Trantham saw hope in genetics.“WhenI was doing molecular biology, I learned that genetics is the root cause of pretty much everything,” she says. “A lot of the promising treatments that are in development for FA are genetic-based therapies, so I really wanted to get more of an understanding of genetics.”
“It's really the combination of understanding the clinical aspect, the molecular aspect and the genetic aspect that's going to help us develop better treatments,” she says. “I was really excited that UF is approaching FA from all those angles.”
Because FA progressively damages the nervous system, Trantham had no time to waste. After attending a medical magnet high school in her hometown of Jupi ter, Florida, she finished her bachelor’s degree in molecular biology from the University of South Florida a year early. Along the way, walking became more difficult. She lost most of the feeling in her legs and required surgery for scoliosis, a common complication of FA, which is caused by a genetic mutation that keeps the body from making the protein frataxin. Without frataxin, cells in the heart, spinal cord and muscles can’t function properly.
She decided to apply to the genetics and genomics gradu ate program at the University of Florida. There, she hoped to work alongside Powell Gene Therapy Center Director Dr. Barry Byrne, whom she first met as a patient, in the epicen ter of FA science and clinical trials.
12 S ummer 2022
S handra Trantham’s research into genetic disease began at age 13, when she snuck a look at her own medical chart.
“I need to move forward with a sense of urgency so these patients get the treatment they're waiting for,” says Shandra Trantham, center, with Barry Byrne and Manuela Corti.
In 2018, Trantham was accepted to UF’s doctoral pro gram and celebrated with orange and blue cupcakes. Then came a curveball: The research had advanced so quickly that by the time she joined Byrne’s lab the following year, the FA research had moved to AavantiBio, the company Byrne founded with fellow UF professor and gene therapy researcher Manuela Corti. While Trantham would still She embarked on a mission to cure her rare disease. Now she’s finding answers for one that’s even rarer.
JonesOctavio
Trantham had been reading about her symptoms, though, and was pretty sure she had figured it out. The glimpse of the chart was confirmation of what she already believed. What she did not believe was that the disease couldn’t be treated. It was curable. She just hadn’t started working on it yet.
Barry Byrne Associate Chair of Pediatrics Director, Powell Gene Therapy Center barry.byrne@ufl.edu Manuela Corti Associate Professor of Pediatrics m.corti@peds.ufl.edu
With Byrne and Corti’s guidance, Trantham is now testing five potential TECPR2 therapies in mice to see which perform the best. It’s data that could inform research for FA and other genetic diseases by shedding light on ways to target the nervous system and strategies to manage immune response to the “Whentherapy.I’m working in the lab, I see the bigger picture: I’m testing the expression of a gene therapy that is going to help people,” she says. “I know what it's like to be waiting for thatShetreatment.”maybeone step closer. In 2019, the year after she had to start using a walker, Trantham began a trial of a medication that has kept her symptoms from progressing. She’s hopeful it will gain FDA approval so she can continue taking it until gene therapy is available to reverse the disease. For now, the drug has reduced her fatigue and improved her stability to the point where she can even wear shoes other than her signa ture high-top Chuck Taylors, previously a must for ankle support. Once she finishes her doctorate, Trantham envisions working at the intersection of advocacy and science. She’s seen the communication gaps between patients, scientists and the government and feels she’s in a unique position to address them. Her men tors
It’s similar to what she’s hoping will happen for her own disease, as Aavan tiBio moves toward clinical trials. It’s tantalizingly close. The gene therapy in development for FA sits in the freezer in her lab. “It's right there,” she says. “I could touch it if I wanted to.”
collaborate with the team pushing the cure forward, she wouldn’t be able to center her Ph.D. project on FA. As a patient, it was good news —
When David and Stacey Ogman’s 4-year-old son, Jordan, was diagnosed with the neurodegenerative genetic disease TECPR2 in 2019, they heard the same devastating outlook Trantham’s parents had heard: no treatment, no cure. But while FA affects thousands, there are just 27 known patients in the world with TECPR2-associated disease. The Boca Raton couple, both UF alumni, reached out to 100 scientists and researchers, hoping someone would take on the challenge of creating a gene therapy for the fatal disorder.Byrne and Corti answered the call a nd so did Trantham.
“I knew how they felt, because when I was first diagnosed, there weren't a lot of clinical trials. Now there's a lot of different approaches in development for FA, but with TECPR2, there's not a lot of research and there's no clinical trials,” she says. “I wanted to help them.”
“That is what goes on in our mind: Every day that passes, there is some progression of the disease,” Corti says. “But at UF, we have all the compo nents to be successful, from basic to translational science and a great clini cal team that has experience with gene therapy. That's not easy to find.”
“Heragree.perspective is invaluable, because she's been there,” Byrne says. “She really understands the urgency.”
“When I’m working in the lab, I see the bigger picture. I know what it's like to be waiting for that treatment.”Shandra
Trantham was one step closer to a commercially available treatment. As a researcher, she wasn’t sure where to focus her efforts. Then two UF grads reached out in need of a miracle.
Trantham JonesOctavio
e xplore 13 SPECIAL ADVERTISING REPORT
In the lab, Trantham now in the fourth year of her Ph.D. program is driven by knowing Jordan’s fate rests in her hands. Because FA impacts her hand coordination, she works with a technician who helps her run experi ments, and uses a mobility device called a LifeGlider that supports her body weight so she can move around the lab without her walker. At the bench, she’s developing ways to deliver a healthy copy of the TECPR2 gene by encasing it in a harmless virus called AAV a technique pioneered at UF in 1983 and first used in models of muscle and heart disease by Byrne. Once the healthy TECPR2 gene is incorporated into the body, patients will be able to make the TECPR2 pro tein as if they didn't have the disease, Trantham explains.
Corti understands the frustra tion of having a cure so close and yet not available. She feels it when she sees patients who could walk when she started researching FA lose their mobility, and wonders if therapies will come in time to bring it back.
Revealing ancestry the Spot’‘Blind 14 Summer 2022
By Alisson Clark
Genetic ancestry shapes health disparities, but most experimentsbiomedicalignoreit
“It feels like a missing piece of the puzzle,” Allen says.
Erika Moore, Josephine Allen, and Connie Mulligan e
xplore 15
In a survey of top biomedical journals, however, just 5 percent of studies reported the demographics of the cells used and the majority were from European ancestors.
Moore, Allen and University of Florida geneticist Connie Mulligan are leading a call for biomedical scientists to factor in the ancestry of cells used in their work.
J
osephine Allen and Erika Moore are keenly aware of the racial health disparities in the conditions they study. But until recently, their experiments l ike those of most biomedical engineers d idn’t incorporate information on ancestry at all. Allen develops materials used in drug delivery and tissue regeneration for cardiovascular disease, the nation’s leading cause of death, with Black Americans 30 percent more likely to die from heart disease than white Americans. Moore focuses on biomaterials that model how immune cells respond, which could be used to test treatments for lupus. Nine out of 10 people with systemic lupus erythematosus are women, with around 60 percent of those women of color.
“It's a huge blind spot,” says Moore, a Forbes 30 Under 30 in Healthcare honoree Allen helped recruit to UF in 2018. “We know that cells have diverging responses to biomaterials depending on genetic ancestry. In any dis ease where we want to apply biomedical sciences, we have to unpack who is being affected by the disease and which cells we’re using.”
JerniganJohn
JerniganJohn
“It's just being really, really intentional about including other groups in your studies however you can — and if not, then at least tell us who you did include so that gap can be identified,”Josephine Allen
16 Summer 2022
Allen, Moore and Mulligan believe that consideration of ancestry could accelerate the pace of discovery for populations and diseases that have been historically underrepresented in research. But to advance their cause, they’d have to get not only researchers, but commercial cell vendors and aca demic journals to revolutionize longestablished practices. With co-author
She points to a 2015 study that found that for the 167 drugs submitted to the U.S. Food and Drug Admin istration for approval between 2009 and 2015, one-fifth showed different responses in cells with different ances tral origins. But in bioengineering, reporting or even considering the demographics of the tissues used in studies is far from the norm. That oversight can hamper scientists’ ability to reproduce the results, mask a lack of diversity in samples used, and make it more difficult to identify areas that need further study, the researchers say.
enthusiastically signed on to the project and began sending her co-authors journal articles, including
“It’s a significant shift,” Allen says, “but it’s not impossible.”
“There's no biological basis to race, but there are certainly biological impacts of racism and discrimination. The experience of living in different racial groups, and particularly racial groups that experience discrimination and racism, is a very real psychosocial stressor that impacts the body,” she says. “Racially specific stressors like racism and discrimination are pretty strong candidates for what might help explain racial disparities in certain diseases.”Moore and Allen knew they needed input from outside of engineering to clearly convey their goals. They looked around the country before finding the expertise they needed right on the UF campus. When they read Mul ligan’s 2021 paper “Systemic racism can get under our skin and into our genes” which theorizes how systemic racism could cause changes in genetic expression that drive health dispari ties they knew they had found the ideal
R ace is a social construct, not a biological one. So why would cells from people of different ancestral lineages behave differently in the Mulligan,lab? an anthropologist who studies genetic and sociocultural fac tors in health disparities, explains.
Genetic ancestry is one way of accounting for variation across samples at the cellular level. If you’ve ever wondered about your own lineage, you might have turned to a home DNA test, which estimates genetic ancestry by looking for hall mark sequences corresponding to dif ferent regions. Ancestry goes beyond genetic markers: It’s also shaped by the social and cultural traditions of your family
Elizabeth Wayne of Carnegie Mellon University, they took their argument to the journal Nature Reviews, laying out their reasons for challenging the status quo in a commentary that sparked interest from the global biological sciences community.
“Yourbackground.genesmight say one thing, and your biological phenotype might tell something, but culturally or psychologically, you might think something very different about your ancestry,” Mulligan explains. “All of
JerniganJohn e xplore 17
“Becausecollaborator.ofConnie's expertise as not only an anthropologist, but also as a geneticist, she really fit the goal of everything we wanted to understand,” MooreMulligansays.
“Your genes might say one thing, and your biological phenotype might tell something, but culturally or psychologically, you might think something very different about your Connieancestry,”Mulligan one linking discrimination to blood levels of cytokines, proteins that help regulate immune and inflammation response. In the 2015 study, AfricanAmerican adolescents who experienced discrimination showed elevated cyto kine levels for more than three years after the “Whenevent.Iread some of those stud ies, I thought, wow, if we get this outlier, maybe that person has received extreme racial discrimination. That's going to significantly skew our results, but we don't take it into consideration right now,” Moore says. “It was mind opening to have those conversations.”
“There is now a call to represent other populations. I hope it ignites others to say, ‘What can we do?’”
Erika Moore 18 Summer 2022
JerniganJohn e xplore 19 SPECIAL ADVERTISING REPORT
The cumulative effect could create more demand for diverse cell lines, spurring vendors to expand their offerings, the researchers say. Efforts like the NIH’s All of Us program which aims to enroll a million participants, especially from underrepresented groups, to share samples and health data a re address ing some of the gaps.
Erika Moore Rhines Rising Star Larry Hench Assistant Professor Herbert Wertheim College of Engineering moore.erika@ufl.edu
“We heard from people on Twit ter, on LinkedIn, people we had never had contact with before, saying, ‘I'm so glad you brought this up. How can we adopt some of your techniques and principles?’” Moore says. Students reached out to ask how to make the topic their field of study.
W hen they published their Nature Reviews paper, Allen, Moore and Mulligan wondered how the field would react.
“It's just being really, really inten tional about including other groups in your studies however you can a nd if not, then at least tell us who you did include so that gap can be identified,” Allen says. “It starts to open the door that maybe we're missing some thing, and we should all take a step back and think about how we can make our work more impactful.”Researchers use either primary cells, which come directly from patients, or cell lines propagated in a lab, which can be cheaper and easier to obtain but don’t perfectly mimic the behavior of primary
cells. Cell vendors could help by pro actively disclosing the demographics of cells instead of making researchers request them. Journals and funding agencies could require disclosure of cell ancestry, which could, in turn, nudge researchers to consider other groups.
“There is now a call to represent other populations,” Moore says. “It's not a mandate, it's a request for increased understanding and commu nication amongst researchers. I hope it ignites others to say, ‘What can we do? Who are we considering in our experi ments?’ It fills my heart with such joy to have these conversations.”
“When you’re publishing on issues of race and racism, it's often very quiet,” Mulligan says. “Sometimes people are afraid to say too much, afraid to say the wrong thing, afraid to say anything.”
Connie Mulligan Professor, Department of Anthropology Genetics Institute College of Liberal Arts and Sciences cmulligan@ad.ufl.edu
Josephine Allen Associate Professor Genzyme Professor of Materials and Engineering Herbert Wertheim College of Engineering jallen@mse.ufl.edu
these phenomena are true. They just measure different aspects of ancestry, and they have very clear impacts on health.”That complexity could be one of the reasons some researchers hesitate to consider ancestral identifiers in their studies. Another may be a reluc tance to reveal that the cells they’re using aren’t very diverse. But trans parency is a meaningful first step, Allen says. “If you're using cells in any capac ity, just report what you're using,” she says. “It's necessary context for your study, whatever your study is about.”
Beyond transparency, the research ers hope their appeal will inspire others to be more intentional in their experimental design.
Not in this case.
“The idea isn’t to say that every experiment needs to include everyone. We know that’s not always going to be possible, and it's not going to apply to all diseases,” Moore says. “But people really need to consider the ancestry of cells when they’re modeling a disease that has a disparity or ancestral com ponent to it. If we’re only studying cells from males or populations with higher genetic ancestry along Euro pean lineages, we’re missing out.”
Researchers around the world tweeted the paper, which Lehigh University Professor Lesley Chow called “a mustread article by leaders in our field.”
The three researchers hope the attention will prompt scientists and engineers to consider what cells they’re using and disclose the demographics when they publish. When Moore gave a talk about the paper at the University of Virginia, a researcher pointed out that ancestry would also be relevant in biomedical engineering for diseases linked to Jewish heritage.
20 S ummer 2022
Photos by Tyler Jones; illustrations by K. K insley-Momberger Can Artificial Intelligence Bring Tastier Produce to our Tables?
By Alisson ClArk
e xplore 21 SPECIAL ADVERTISING REPORT
O
All they’d have to do is teach a computer to taste. ere, try this one,” Muñoz says, offering a plump berry of a variety called Optimus, named for the Transformers character Optimus Prime because it can be harvested by machine. It’s firm, sweet, with a hint of acidity.“Keep that flavor in your memory, then try this one,” Muñoz says, offering a variety yet to be named.
It’s not easy to retain the memory of a blueberry, espe cially while tasting a different one. Plant breeders not only “H
applications extend far beyond blueberries, a growing sector of Florida’s $182.6 billion agriculture industry. Their brainchild, the AI Connoisseur, would not only give Florida farms an edge, but make healthy food more palatable to more people, bringing varieties with heirloomquality flavor within everyone’s reach.
But while advances in plant breeding have shortened the time from lab to table, developing a new cultivar and taking it to market can take a decade or more. Muñoz and his colleagues at the University of Florida envision a quicker method: exploring the natural varia tions in plant genetics using artificial intelligence. The Byte test
n a farm outside Gainesville, plant geneticist Patricio Muñoz strides through rows of shoulder-high blueberry bushes. He’ll log up to 10 miles a day traversing experimental plots where a single 4-acre field can hold 300 new varieties, berries of unparalleled deliciousness that you can’t find in any farmer’s market or grocery store yet.
Along the way, he conducts what’s known as a bite test, sampling each variety and noting its flavor. Some have undertones of rose, some of raspberry; some are bright and floral, others as sweet as jelly.
With taste panels costing up to $4,000 and requiring up to 100 people, hun dreds of potentially delicious cultivars are eliminated before reaching that point — essentially by educated guess, says Marcio Resende, a sweet corn breeder and one of the leaders of the AI Connoisseur research.
Denise Tieman
“It’s very subjective,” he says. “Not only is it the opinion of a single person, but there’s some bias there, because no matter how good the fruit or vegetable is, by the end of the day you’re tired of eating it. The last one is never going to taste as good as the first.” If the team could use taste-test data to teach artificial intelligence to predict what a typical customer enjoys, they could avoid that bias. But unlike single traits such as sweetness, acidity and bitterness, flavor is notoriously tricky to pin down.
B
iochemist Denise Tieman scoops chunks of juicy ripe tomatoes from a cutting board into a long plastic tube, seals it, then carries it to a machine that will tell her the components that create its taste. Using a procedure developed at UF, she loads the tubes into a vacuum pump that samples the volatile organic compounds (VOCs) the tomatoes emit.
22 S ummer 2022 do this, but also train their palates to reflect the average consumer’s preferences, not their own. They use these skills to winnow down acres of potential candidates to just a handful of varieties, which then go to panels of taste testers who select their favorites.
UF’s Institute of Food and Agri cultural Sciences has been running such taste panels for decades, asking volunteers to rate the taste, texture and appeal of new varieties, as well as what they’d pay for them. If a new variety is deemed marketable, it then goes to growers and, eventually, the groceryWhatstore.canAI bring to the table?
Outside of the plant breeding world, VOCs might be more commonly associated with paint fumes than fresh “Flavor’s been terribly difficult to breed for. There’s been no good way to define flavor or know how to breed for it.”
e xplore 23 SPECIAL ADVERTISING REPORT Patricio Muñoz
I
Over decades of selection for traits that made tomatoes easier to grow, harvest and ship, many variet ies lost the heady, quintessentially summertime aroma that made them the world’s most popular produce.
n Muñoz’s office, on the outer reaches of the Gaines ville campus in a build ing surrounded by greenhouses and groves, Muñoz and Resende look over dozens of clamshell containers holding the blueberry varieties headed to taste testing this year. They cover the sur face of Muñoz’s desk, but with the AI When you bite into a fresh blueberry or tomato and taste its sugar and acid on your tongue, that’s just the beginning. As you chew and swallow, VOCs reach olfactory receptors in your nose and the back of your throat, and flavor emerges.
“Flavor’s been terribly difficult to breed for,” Tieman says. “There’s been no good way to define flavor or know how to breed for it.”
For each food crop, different vola tiles take center stage, and it’s not just their presence but their interaction that makes it mouthwatering. Tieman’s mission is to keep the modern tomato’s practical traits while adding the critical components back in. But while sugar and acid are easy to measure, VOCs have presented a challenge.
If you’ve ever tasted a tomato with out much flavor a nd who hasn’t lost VOCs are the culprit. E-2-hexenal and phenylacetaldehyde don’t sound delicious, but they’re some of the 400 volatiles that make a tomato a tomato, contributing sharp, leafy aromas for the former, a mix of hyacinth, honey and cocoa for the latter.
When you bite into a fresh blue berry or tomato and taste its sugar and acid on your tongue, that’s just the beginning. As you chew and swallow, VOCs reach olfactory receptors in your nose and the back of your throat, and flavor emerges. (That’s why foods don’t taste right when your nose is stuffy. Smell loss from COVID-19 also comes from a breakdown along the olfactory-perception highway.)
CavityNasalReceptorsOlfactory Taste
24 S ummer 2022 veggies, but they form the essence of flavor, and what we don’t know about them far outpaces what we do.
“It was through UF’s initiative to bring AI to every classroom that a student like me, in horticultural sci ences, could have opportunities and resources to perform AI research,” he Bysays. matching taste tests with each variety’s chemical composition, the researchers hypothesized, they could pinpoint key compounds for differ ent crops, yielding targeted pathways toward flavor. And with an accurate AI prediction model, they could test thousands of potential varieties by asking the AI Connoisseur to extrapo late how consumers would like them a quicker route to better breeds.
With the AI Connoisseur, however, that could Resendechange. andMuñoz teamed up with research scientist Felipe Ferrão and doctoral student Vincent Colantonio to code the AI Connoisseur and run its machine-learning models on UF’s HiPerGator AI supercomputer — an opportunity Colantonio says was only possible because of UF’s commitment to infusing AI across the curriculum.
They hope tastier produce entices consumers to come back for more — a boon for the 90% of Americans whose fruit and veg intake falls short of the recommended amount.
Marcio Resende Assistant Professor of Horticultural Sciences mresende@ufl.edu Denise Tieman Research Assistant Professor of Horticultural dtieman@ufl.eduSciences
Patricio Muñoz Associate Professor of Horticultural Sciences p.munoz@ufl.edu
In a study published in the journal PNAS this year, they showed that their model works: It was able to accurately predict what consumers liked and show the compounds that contributed to flavor in blueberries and tomatoes. The method could be applied to any food crop where the data is available, such as citrus and strawberries, Resende says. The technology won’t replace taste testing: It doesn’t evaluate factors like texture, appearance, or cultural factors that can influence our preferences. But it can get tomorrow’s healthy foods on our plates sooner. Next, Tieman envisions identifying genetic markers that correlate to those key compounds, allowing scientists to begin selection on tiny plants instead of waiting for them to bear fruit.
“Processed foods are engineered for you to love them,” Muñoz says. “Why can’t we use technology to do the same thing for fruits and vegetables?”
e xplore 25 SPECIAL ADVERTISING REPORT
Marcio Resende
Connoisseur, the berries he can test could fill a three-car garage.
Muñoz imagines a produce sec tion where boutique blueberries bear the kind of descriptors you’d find on coffee, beer or chocolate: sweet and jammy types for kids; aromatic, floral ones for more sophisticated palates.
LehanBrianne
“We can learn a lot about mam malian and human tooth development from looking at sharks,” says Fraser, an assistant professor of biology. “They lay down almost the exact same mate rials, using the same cell types with the same genes.”
Gareth Fraser B y Natalie vaN HooSe Could sharks teach us to regrow teeth as we age?
W
SPECIAL ADVERTISING REPORT
Fraser grew up fossil hunting and fishing along the sweeping coastline of Wales in the village of Ogmore-bySea. When his grandparents brought him a pair of pufferfish skeletons from travels in Egypt, he became incurably captivated by their strange forms. Throughout his university studies and beyond, his curiosity encompassed paleontology, evolutionary develop mental biology and dentistry. He found himself pursuing an unconven tional question: Do fish and humans develop teeth in the same way? Surprisingly, we do. Fraser’s research has shown that our teeth and those of all fishes, from hammerheads to deep-sea anglerfish, arise from the same band of tissue, a structure known as the dental lamina. In humans, the dental lamina degrades after we grow our adult teeth, but fish maintain this tissue throughout their lifetime, enabling them to create a continuous supply. Sharks are the ultimate masters of tooth regeneration, with some spe cies growing a new set of teeth every twoThisweeks.raises a tantalizing possibility. If sharks can regrow teeth, why can’t we?
It's a controversial approach to studying teeth. Mice, not sharks, have been the go-to model for human tooth development for decades. Many sci entists have argued mammal teeth are special, featuring unique innovations not found in other animals. Fraser’s research, however, suggests our teeth have much more ancient roots.
hen UF evolutionary biologist Gareth Fraser gives a talk titled “Why sharks are the future of dentistry” at dental conferences, there are a lot of raised eyebrows. But slide by slide, he outlines the surprising structural similari ties between human and shark teeth and shows how the genetic pathways undergirding our tooth development are the same.
“The genetic features that sharks retain may be what we need to reinvigorate the human system.”
The American College of Prosthodon tists estimates that more than 36 mil lion Americans do not have any teeth and 120 million people in the U.S. are missing at least one tooth. These num bers are expected to grow in the next twoAtdecades.UF,Fraser’s lab is culturing and studying sharks’ “immortal” tooth cell lines in hopes of uncovering new human dental therapies. To locate the genetic switches that enable sharks to keep making teeth, Fraser is manipu lating some shark embryos to stop developing teeth essentially “gummy sharks” a nd others to kick their tooth production into hyperdrive. By comparing human tissues to the active dental lamina in sharks, his team aims to identify key gene sets and signaling pathways essential for tooth production.“Thegenetic features that sharks retain may be what we need to rein vigorate the human system,” he said.
But Fraser’s not stopping there i f humans could regenerate simple organs such as teeth, why not more complex“Animalsones?regrow things pretty well,” he says, pointing to axolotls, salamanders that can redevelop limbs and even parts of their brain. Lizards such as anoles can discard and regrow their tails at will. At the root of regeneration is developmental tissue, the malleable underpinnings that give embryos across the animal kingdom a greater ability to recover from“Thissetbacks.isone of the things that makes me so excited about this sci ence,” he says. “There's so much that we can learn about these sorts of processes, these embryonic transitions. We sometimes overlook this beautiful process of change.”
“There's so much that we can learn about these sorts of processes, these embryonic transitions. We sometimes overlook this beautiful process of change.”
Gareth Fraser It’s doable, Fraser says. His work has pinpointed pockets of still-viable stem cells in the remains of the human dental lamina deep in our gums. These cells could help us unlock the ability to regenerate our own teeth increas ingly a need as humans live longer.
28 S ummer 2022
Gareth Fraser Assistant Professor of Biology g.fraser@ufl.edu Scanning electron microscope images of catshark teeth (top row) show their development from the embryonic through juvenile stage. Fraser uses computational models to compare shark tooth development to that of mammals (seal, middle row) to under stand how sharks regrow teeth. He also studies denticles (CT scan at left), the toothlike structures that armor sharks’ bodies.
Whenwounds.Fraser began his Ph.D., he was interested in the idea of novelty in evolution. Over time, however, he has become convinced that few features are truly new. “You’re building upon structures that are already there or building on networks of genes that are already there. For some other reason, they've just been repurposed or coopted,” he Likewise,says.Fraser’s work co-opts features derived over millions of years of evolution, repurposing them in innovative ways. The common thread throughout his research is his own curiosity.“I’mdefinitely a scientist who will only do things that are fun. Working on these strange models gives me more joy than working in a mouse lab.”
e xplore 29 SPECIAL ADVERTISING REPORT
Fraser is also studying shark den ticles, the intricate “skin teeth” that armor their bodies and help them reduce drag as they move through water. In 2021, he and collaborators at Harvard and Yale Universities secured a $1.7 million grant from the National Science Foundation to examine the characteristics and patterns of shark denticles. Better understanding these structures could help engineers create artificial shark skin for airplanes, boats and cars to improve aerodynamics and reduce fuel emissions. Fraser also sees opportunities to use these patterns to explore new approaches for healing skin
eDNA leads the way LehanBrianne DNA “fingerprints” left behind by sea turtles offer scien tists a simple, powerful way of tracking the health and whereabouts of these endangered animals, a key step forward in their conservation.
A study led by UF researchers is the first to sequence environmental DNA, or eDNA, from sea turtles genetic material shed as they travel over beaches and in water. The research project is also the first to successfully collect animal eDNA from beach sand. The techniques could be used to trace and study other kinds of wildlife, advancing research and informing conservation strategies. The study was pub lished in the journal Molecular Ecology Resources.
Nearly all of the planet’s sea turtle species are endangered and face a multitude of threats, including warming tempera tures, habitat destruction and degradation, disease, hunting and pollutants such as plastics. Conserving sea turtles is further complicated by the fact that current survey methods rely on spotting them in one of their multiple habitats in the open sea, coastal ecosystems or on beaches where they B y Natalie vaN HooSe
“We wanted to test the boundaries of this technology, which hadn't really been applied to sea turtles before and certainly not on sand,” said David Duffy, assistant professor of wildlife disease genomics. “This is a way to survey areas for elusive animals or species that can be hard to study oth erwise. It’s essentially wildlife forensics.”
A team led by Duffy and UF graduate students Jessica Farrell and Liam Whitmore created techniques that can identify the presence of green turtles, Chelonia myda s, and loggerheads, Caretta caretta both endangered species — via DNA in a small scoop of sand or a liter of seawater. Minuscule amounts of DNA revealed not only which species of sea turtles had recently passed through, but their place of origin and the subpopulation to which they belonged. On sand, the team was even able to extract viable DNA from a crawl track made by a single loggerhead hatchling, which weighs about as much as a dozen paperclips.
“By optimizing eDNA practices for sea turtles, we had a much better success rate of identifying them in an area than with traditional survey methods,” Duffy said.
The methods could help scientists verify where sea turtles are living and how their range and numbers are shifting over time, Duffy said. eDNA also omits the need to take tissue and blood samples, which can be stressful for turtles, par ticularly nesting females.
LehanBrianne LehanBrianne nest. This makes it difficult to monitor their numbers, genetic diversity and overall health and tailor conservation efforts accordingly, Duffy said.
Before testing eDNA methods in the wild, the team refined their techniques in the tanks and sand occupied by recuperating turtles at the Whitney Laboratory. The scien tists found that eDNA from sea turtle nests remained viable for more than a day.
“You can say not only whether the species is present or absent, but you can potentially start to measure how many of those species are present, which is not easy to do for marine animals,” he said.
e xplore 31 SPECIAL ADVERTISING REPORT
The project would not have been possible without the efforts of a consortium of faculty, graduate students, post doctoral researchers, hospital staff and citizen scientists, Duffy
“UF’semphasized.WhitneyLab is the only specialized sea turtle hos pital in the world that's co-located with a research institute,” said Duffy, who joined the Whitney Lab in 2020. “We have frontline rehabilitation and wildlife conservation work going hand-in-hand with advanced molecular biology research, which lets us address questions that can’t really be addressed anywhere else.”
David Duffy Assistant Professor of Wildlife Disease Genomics duffy@whitney.ufl.edu
The team could also ascertain sea turtle pathogens in eDNA samples, including the main virus that causes fibropapillomatosis, an increasingly common cancer that causes cauliflower-like tumors on sea turtles’ skin, eyes, mouth and internal organs. About 50% of green turtles that strand on Florida beaches are afflicted with these tumors, which can become so debilitating that they impact turtles’ ability to catch food and swim. eDNA techniques could pinpoint specific variants of the virus and its concentration in the water column helpful advancements in following its spread and developing potential treatments in the future,
“Some of these threats are quite new and even ones that existed for a longer time are getting worse,” said Duffy, who is based at UF’s Whitney Laboratory for Marine Bioscience and Sea Turtle Hospital, one of the world’s top centers for sea turtle rehabilitation, research and education. “That's why it's very important for us to have these DNA tools to be able to get a proper handle on what's happening to the popula tion in real time.” eDNA techniques were originally developed to extract and analyze DNA from microbes in soil and water. Now, however, scientists are leveraging this technology to detect the presence of much larger animals, which regularly leave behind small amounts of genetic material via skin, hair, scales, feces or bodily fluids.
DuffyThesaid.next step in the research project will focus on conser vation genetics u sing DNA to capture a snapshot of how many individual animals live in an area and how genetically diverse they are, a crucial predictor in how they will weather threats, Duffy said.
“Surpassing the $1 billion research milestone reflects UF’s continued rise as one of the leading research universities in the United States. This number represents far more than dollars — it represents the value of these researchers’ remarkable intellect and talent and its impact on our state, our nation and the world.”
With support from NASA, researchers
– UF Vice President for Research David Norton research.ufl.edu/billion from first
UF were the
Explore Magazine Box Gainesville,115500 FL 32611-5500 Gainesville,U.S.OrganizationNon-ProfitPostagePAIDFLPermitNo.94
to grow plants in lunar soil. Scan this code with your camera to join our mailing list or update your mailing address.
