UF Explore Magazine | Spring 2019 by University of Florida Research Explore Magazine

SPRING 2019

Hive Help Keeping Honey Bees Healthy

John Jernigan

Spring 2019, Vol.â&#x20AC;&#x2026;24, No.â&#x20AC;&#x2026;1

About the cover: Bees are placed inside these cages to run toxicology tests. The bottom of the cylinder is a disk with wax. Various insecticides at different levels can be placed in the wax, and then the effect on the honey bees can be observed and measured.

Extracts

Research Briefs

The Researcher Within

NSF Fellowships Nurture Young Scientists

Putting Novel Spinal Cord Therapy To The Test

Drilling Down Lake Beneath Antarctic Ice Reveals Its Secrets

Hive Help Keeping Honey Bees Healthy

When Less Oxygen Heals

Creating The World To Come

Science And Art In The Anthropocene

Dr. David Norton Vice President for Research Board of Trustees Mori Hosseini, Chair David L. Brandon Ian M. Green James W. Heavener Leonard H. Johnson Thomas G. Kuntz Daniel T. Oâ&#x20AC;&#x2122;Keefe Rahul Patel Marsha D. Powers Jason J. Rosenberg Robert G. Stern Katherine Vogel Anderson Anita G. Zucker Explore is published by the UF Office of Research. Opinions expressed do not reflect the official views of the university. Use of trade names implies no endorsement by the University of Florida. ÂŠ 2019 University of Florida. explore.research.ufl.edu Editor: Joseph M. Kays joekays@ufl.edu

The Conversation

Dr. Kent Fuchs President

Mapping The Body's Cells

Art Director: Katherine Kinsley-Momberger Design and Illustration: Katherine Kinsley-Momberger Ivan J. Ramos Writers: Alisson Clark Michelle Koidin Jaffee Joseph Kays Cindy Spence Photography: Kristen Grace John Jernigan Jesse Jones Tyler Jones Web Editor: Jewel Midelis Copy Editor: Bruce Mastron Printing: StorterChilds Printing, Gainesville Member of the University Research Magazine Association www.urma.org

Kristen Grace/Florida Museum

In February, Florida Museum of Natural History Director Doug Jones and Jaret Daniels, associate director of the McGuire Center for Lepidoptera and Biodiversity, led a group to witness millions of monarch butterflies overwintering in Ocampo, Mexico. UF is a world leader in butterfly research, in part because of two world-renowned researchers who died last year — Thomas Emmel, the founding director of the McGuire Center, and Lincoln Brower, who did some of his most important work on monarch migrations at UF between 1980 and 1997. 4 Fall 2018

Creating Academic Leaders

art of the mission of the UF Office of Research is to “educate the next generation of leaders” and this issue of Explore illustrates the vital role the university plays in the lives of graduate students and that graduate students play in the life of the university. The many graduate students featured in this issue are representative of about 12,000 students pursuing master’s or doctoral degrees in every department on campus. These students are vital to the success of UF’s research enterprise, which in 2018 had a record $865 million in expenditures, surpassing our previous record in 2017 by $63.6 million. They also share their knowledge with undergraduates as teaching assistants and are increasingly involved in our technology transfer efforts, with many starting their own businesses. It’s hard not to be impressed by the range of research being conducted by UF’s 80 NSF Graduate Research Fellows since 2013. From anthropology to ecology and nuclear engineering to political science, these students are addressing some of the most vexing issues of our day. The same can be said of Christina Davis, who traveled to Antarctica to help us better understand what is happening in the giant lakes that lie beneath the ice cap. A report several years ago by the Council of Graduate Schools argued that “a strong link exists between U.S. graduate education, the production of knowledge, and economic and social prosperity.” “The United States needs a cadre of highly skilled leaders and experts in a variety of fields to address current and future challenges,” the report said. “Increasingly, graduate school is where future professionals obtain the knowledge and skills needed to solve big, complex problems.” Engineering Professor Greg Sawyer sees a lot of similarities between the relationship faculty advisers have with their graduate students and the relationship Leonardo da Vinci had with his students. Addressing graduating doctoral students last summer, Sawyer said, “In the Prado in Madrid there is a second Mona Lisa … It was likely painted by one of his students, Francesco Melzi, working alongside Leonardo. What a great thing! Leonardo didn’t simply give Francesco a finished painting to copy;

David Norton

Vice President for Research

it is clear that they created the painting together. As mistakes were made and corrected and details changed, they were changed together. “I think about that vibrant lab often. How much of Leonardo da Vinci’s work was really for his advisees? Who were all the notebooks for? Leonardo reportedly maintained a group of six students. It was Francesco who kept Leonardo’s notebooks: the advisee carrying the lessons forward, sharing the notebooks and teachings of Leonardo with his own students. We might never know the breadth of Leonardo’s work, his methods and experiments, his work in mechanics and medicine, and all of the imaginative engineering designs if not for Francesco.” The University of Florida greatly values its graduate students, for their imagination, their commitment to science and scholarship, and their dedication to teaching. We look forward to telling more of their stories in Explore. 5

E tracts Better Patient Care AI system delivers fast, accurate patient data

n a hospital’s intensive care unit, doctors get a cascade of data about each patient’s condition that can be challenging to quickly organize and interpret. Now, University of Florida researchers have developed and successfully tested an artificial intelligence system that delivers streamlined and timely details about crucial changes in a patient’s condition. The system, known as Deep Sequential Organ Failure Assessment, or DeepSOFA, works by collecting, organizing and presenting a patient’s medical data so that doctors can make nimbler, better-informed decisions. “As a doctor, you want the big picture. You want a complete, timely snapshot that tells you how your patient is doing,” said Dr. Azra Bihorac, co-author of the findings and a professor of medicine and surgery in the College of Medicine. “This is the next generation of intelligentdecision support.” Using data and outcomes from prior patients to test DeepSOFA, the researchers found that it delivers more accurate predictions of inhospital mortality than other models. The findings were published in the journal Nature Scientific Reports. DeepSOFA buys crucial time by indicating which intensive care unit patients may need a lifesaving intervention to prevent potentially fatal conditions, Bihorac said. DeepSOFA can be a powerful predictive tool to help doctors determine how a

6 Spring 2019

patient’s condition is trending and what may be causing that change, she said. “It’s very hard for us to efficiently review all of a patient’s data because of the way it is scattered. As a human, you can’t always put all of a patient’s numbers together with the speed and precision of a computer,” Bihorac said. To develop DeepSOFA, her team worked with Parisa Rashidi, a UF assistant professor of biomedical engineering and co-author of the paper. Rashidi and doctoral student Benjamin Shickel spent several years working with Bihorac and her team to develop the algorithm that powers the program. The system uses “deep learning,” a type of artificial intelligence that automatically processes large amounts of raw data and discovers latent patterns within those numbers. The result: A real-time, autonomous system that gives doctors an efficient but thorough look at a patient’s condition and how it is trending. It is the first time that deep-learning technology has been used to generate patient viability scores, the researchers said. To validate DeepSOFA’s effectiveness, the researchers used it to analyze data from more than 85,000 prior patients at UF Health Shands Hospital and Beth Israel Deaconess Medical Center in Boston. DeepSOFA’s ability to accurately predict patient mortality was measured against a traditional model of SOFA that was devised elsewhere about 20

years ago. Both models were tested using 14 variables that are key indicators of patient health, including central nervous system, respiratory and cardiovascular functions. Among both patient groups, DeepSOFA showed “excellent” performance compared with the traditional SOFA model, the researchers found. DeepSOFA accurately predicted in-hospital mortality for an entire ICU stay in 90 percent of cases, compared with 79 percent mean accuracy for the traditional model. The traditional SOFA model tended to underestimate the severity of illness and predict relatively low chances of death, whereas DeepSOFA was found to better quantify illness severity and death risk. DeepSOFA also outperformed the traditional model when studied in a singlepatient case, the researchers found. The female patient was admitted to a hospital and later died from an obstructed blood supply to a lung. Two days after being

admitted, DeepSOFA predicted a 50 to 80 percent probability of death, compared with a 5 percent prediction by the traditional SOFA model. In the final five hours before death, DeepSOFA estimated a 99.6 percent chance of mortality compared with 51.5 percent for traditional SOFA. DeepSOFA’s accuracy during the tests on the single patient’s data was particularly notable, Rashidi said. While artificial intelligence is a powerful tool to augment doctors’ decision making, it comes at a price: Collecting patient data in real time and pushing it though an analytics engine such as DeepSOFA would require extensive initial investments, Bihorac said. Next, the researchers will work on the technical infrastructure needed to integrate DeepSOFA with electronic health records in real time, which would allow it to run autonomously in hospital settings, Rashidi said. Doug Bennett

Smoking During Pregnancy Discount stores’ tobacco sales tied to pregnant women smoking

obacco sales at two national dollar-store chains may have negatively impacted the smoking rate among pregnant women in the Southeast United States, University of Florida Health researchers have found. Smoking during pregnancy was found to be associated with increased tobacco availability at thousands of dollar stores in the region, the study concluded. The findings were published in the journal JAMA Pediatrics. “The rate of smoking during pregnancy has been coming down but rates are nearing stagnation in counties that have the greatest increases in tobacco availability due to this change in corporate policies of the dollar stores,” said Jaclyn Hall, an assistant research scientist in the UF College of Medicine’s Department of Health Outcomes and Biomedical Informatics and lead author of the study. To establish their findings, the researchers used publicly available data to track smoking habits and shifting tobacco sales policies at a major pharmacy and several dollar store chains. In late 2012 and early 2013, the nation’s two largest dollar-store chains started selling tobacco products in approximately 8,300 southeastern stores. Two years later, the nation’s largest pharmacy chain ended tobacco sales at its 2,500 stores. As a net result of these policy changes, access to tobacco products across the region increased. The researchers looked at trends from 2011-12 and

2015-16 in counties of six large southeastern states: Florida, Georgia, Mississippi, North Carolina, South Carolina and Tennessee. They concluded that increased access to tobacco may be inhibiting programs to help reduce tobacco use even after factors such as sociodemographics and tobacco-control efforts were considered. The researchers chose the Southeast because dollar stores are most prevalent in this region, and smoking rates are among the highest in the nation. Smoking during pregnancy is one of the leading preventable causes of negative birth outcomes such as premature birth and low birth weight, Hall noted. The study found the biggest declines in the rate of smoking during pregnancy occurred in counties that had no increase in tobacco retailers or even a decline in the number of stores due to the pharmacy’s decision not to sell. “This study shows that a

large retailer’s decision about selling tobacco products can have a profound impact, positive or negative, on community health,” Hall said. “It would greatly change the tobacco retail landscape if other pharmacies and companies stopped selling tobacco and demonstrated their commitment to Americans’ health.” After controlling for demographic variables and smoke-free laws, changes in the number and concentration of tobacco retailers was the most significant factor in the rate of decline of smoking during pregnancy, the researchers found. Among pregnant women in lower-income communities, smoking rates fell only 3.6 percent in areas where tobacco retailers increased the most, while the rate fell 12 percent in areas with smaller increases in tobacco retailers. The same trend was found in high-income communities: Smoking rates for pregnant women declined 20.3 per-

cent in areas with smaller increases in tobacco retailers — more than twice the improvement that was found in places where tobacco sellers proliferated. “The six states that we studied all declined to expand Medicaid under the Affordable Care Act,’’ Hall said. “Expanding health coverage would have offered more clinical smoking-cessation programs to low-income individuals.” The findings could be used by local officials to develop property zoning and tobacco sale licensing guidelines to reduce clusters of tobacco retailers, especially near schools, said Ramzi Salloum, UF assistant professor of health outcomes and biomedical informatics and senior author of the study. Counties could enact density rules for tobacco sellers similar to the regulations on bars, he said. Likewise, states should consider adequate funding for smoking cessation and health communications programs, the researchers noted. Next, the researchers plan to further analyze information about tobacco retailing and smoking habits at the neighborhood level. That, Salloum said, could help guide policy decisions about the concentration of tobacco retailers in communities. “The action by these dollar stores goes against decades of progress in tobacco control and compromises that progress,” he said. “It’s contributing to the disparities in smoking rates in the communities where dollar stores are prevalent.” Doug Bennett

E tracts Fighting Zika Dengue immunity may reduce Zika infections

n the epicenter of the Zika epidemic in northeast Brazil, 73 percent of people living in an urban slum in Salvador were infected in 2015, but a new study finds that those with immunity to dengue, a genetically similar virus, had a reduced risk of infection with Zika. “This study is the first to demonstrate that immunity to dengue can protect against Zika infection in human populations,” said Derek Cummings, a University of Florida biology professor and a researcher with UF’s Emerging Pathogens Institute. Cummings worked with a team led by the Brazilian Ministry of Health that included scientists from the University of California, San Francisco, the Federal University of Bahia, the University of Pittsburgh and the Yale School of Public Health.

For the study, published in the journal Science, the team examined a cohort of 1,453 individuals participating in a long-term health survey in Pau da Lima, Salvador, Brazil, who may have been exposed to Zika during the 2015 outbreak. Using multiple immune assays, the team characterized this cohort’s immunity to dengue before and after the Zika outbreak and identified Zika infections. To do this, the team developed a novel assay that measured immunoglobulin G3 responses to Zika, a specific antibody that recognizes Zika. “One of the challenges in studying dengue and Zika is distinguishing immunity to one virus from the other. We used multiple methods to disentangle immune responses to each virus,” said Federico Costa, an associate professor

at the Federal University of Bahia and an associate adjunct professor at the Yale School of Public Health. A majority of individuals in the cohort had been infected with dengue before the Zika outbreak. For those with prior immunity to dengue, each doubling of antibodies was associated with a 9 percent reduction in risk of Zika infection. “Even though there was protective immunity in the population, this community was heavily infected,” said Albert Ko, a professor and chair of epidemiology at the Yale School of Public Health and co-corresponding author with Cummings. “Dengue immunity reduced individuals’ risk, but still 73 percent of the population was infected by Zika.”

The results provide evidence that acquired immunity to the Zika virus has driven Zika transmission to low levels. “The Zika pandemic has created overall high rates of immunity to this virus in the Americas, which will be a barrier for outbreaks in coming years,” said Isabel Rodriguez-Barraquer, an assistant professor at University of California, San Francisco and one of the lead authors of the study. Rachel Wayne

Inactive Impacts Sedentary lifestyle negates heart benefits of healthy weight adults

Arch G. Mainous III

8 Spring 2019

new University of Florida study may provide some extra motivation to exericse. Researchers have found that low levels of physical activity can put healthy weight adults at the same risk for cardiovascular disease as adults who are overweight. “Our study demonstrates that a sedentary lifestyle counters the benefit of being at a normal weight when it comes to heart disease risk,” said lead investigator Arch G. Mainous III, chair of the Department of Health

Services Research, Management and Policy in the UF College of Public Health and Health Professions. “Achieving a body mass index, or BMI, in the normal range shouldn’t give people a false sense of confidence they’re in good health. If you’re not exercising, you’re not doing enough.” The study, which appears in the American Journal of Cardiology, found that 30 percent of U.S. adults at a normal weight are at increased risk of heart attack

or stroke. These adults had higher levels of belly fat, shortness of breath upon exertion, unhealthy waist circumference or less than recommended levels of physical activity, the UF researchers say. “We have traditionally thought that people with a normal BMI are healthy and at low risk for heart disease, but increasingly we are finding that how much you weigh is not necessarily a measure of good health,” said Mainous. “Sedentary lifestyle

Einstein Medal Professor Awarded Top Physics Prize

lifford Will, distinguished professor of physics in the UF College of Liberal Arts and Sciences, is the recipient of the 2019 Albert Einstein Medal from the Albert Einstein Society. Will is being recognized for his contributions to physics and to the Theory of General Relativity, including the post-Newtonian expansions of the Einstein field equations and their confrontation with experiments. A formal award ceremony will take place in Bern, Switzerland, on June 6. “Professor Will is joining an extraordinary group of awardees, and his prize is well deserved,” said Liberal Arts and Sciences Dean David Richardson. “He has made many important contributions to the Theory of General Relativity and is

the acknowledged world expert on interpreting experimental tests of the theory. We are honored to have him in our college, sharing his knowledge, creativity and spirit with the next generation.” Will is the author of “Was Einstein Right?” in which he focuses on verifying Einstein’s theories through experiments. Will’s research on the observable and testable consequences of relativity, which includes gravitational radiation, theoretical analyses of experimental tests of relativity and relativistic effects of massive black holes, has won him worldwide renown. “It’s very gratifying to receive this award. Just looking at that list of other winners, it made me feel very honored

to be included among those names,” Will said. Past winners include Stephen Hawking, Roger Penrose and eight Nobel laureates. The Albert Einstein Medal has been awarded annually since 1979 to individuals for

their outstanding scientific findings, work or publications related to Albert Einstein.

markers may play a better role in predicting cardiovascular disease risk.” For the study, the investigators analyzed data from the National Health and Nutrition Examination Survey, a nationally representative study that collects data from a combination of interviews, physical examinations and laboratory tests. The study focused on participants ages 40 to 79 who did not have a previous diagnosis of coronary heart disease, stroke or heart attack. Researchers examined participants’ sagittal abdominal

diameter, which is a measure of fat in the gut region, and waist circumference as well as self-reports on the amount of moderate to vigorous physical activity, the amount of time spent sitting and whether they experienced shortness of breath either when hurrying or walking up a slight hill. In addition, researchers calculated the American College of Cardiology and the American Heart Association, or ASCVD risk score, of participants. The ASCVD risk score uses weighted variables, including age, sex, race/ethnicity, smoking

status, diabetes status, cholesterol, blood pressure and blood pressure medication status, to calculate individuals’ risk of having a heart attack or stroke within the next 10 years. A score of 7.5 percent or higher is considered high risk. The investigators found the rate of high ASCVD risk score among people who are overweight was similar to the rate among people who had a normal BMI, but had indicators of a sedentary lifestyle. For those looking to increase their activity level, Mainous suggests reviewing

the Centers for Disease Control and Prevention’s physical activity guidelines, which recommend at least 150 minutes of moderate intensity exercise a week for adults. Exercise should include a combination of aerobic activity and strength training.

Megan Ellinghausen

Jill Pease

E tracts Future Farming Robots and information technology may rule the roost

griculture, one of the world’s oldest vocations, is also one that continues to reinvent itself with new technology. From the introduction of the steel plow to automated tractors to modern fertilizer applications, technology has improved effectiveness and increased efficiency. Now, two University of Florida professors say robots and information technology will rule the roost on farms in the coming years. University of Florida Institute of Food and Agricultural Sciences Professors Senthold Asseng and Frank Asche cowrote an article published in the journal Science Robotics in which they say: “the farmers

of the future are likely to be data scientists, programmers and robot wranglers.” “I think we will see the first farm trying to put all this technology together in the next few years,” Asseng said. Asseng works as a faculty member in agricultural and biological engineering and is a fellow of the UF/IFAS Institute for Sustainable Food Systems (ISFS). Asche is a faculty member in the program on fisheries and aquatics in the School of Forest Resources and Conservation, and is also affiliated with the ISFS. In the face of global challenges to produce more food more sustainably, the researchers urge scientists and

growers to radically rethink their approaches to farming. Farmers face constraints such as high labor costs, dwindling land on which to grow crops and access to fresh water — due to changing climate and population growth. “We have already become accustomed to the idea of autonomous machinery, like tractors navigating their way up and down a field,” said Asseng. More recent technological advances include robots and drones that can operate autonomously 24/7, collect large amounts of farm data and carry out tasks on the field. The collected information can be used to optimize food production and resource use,

“The constant monitoring and collection of information from sensors in the field or from sensors attached to livestock will make it possible to trace a food product from farm to fork.”

Tyler Jones

— Senthold Asseng and Frank Asche, Science Robotics

the researchers say, resulting in higher yields with less fertilizer and pesticides. Heavy machinery, used in place of higher labor costs, has compacted soil, leading to reduced root growth, lower soil fertility and eventually, less yield, the researchers say. Replacing heavy machinery with autonomous light-weight robots and drones can overcome the soil compaction issue and make food production more sustainable. Another advantage they cite from technological advances is food traceability. “The constant monitoring and collection of information from sensors in the field or from sensors attached to livestock will make it possible to trace a food product from farm to fork,” the researchers wrote. All the components of the future farm already exist, including decision software for crop management, said Asseng. He sees all these innovations benefitting society, the way we farm and the environment. It will help with increasing food production and at the same time increase sustainability. “I think the trend is clearly there since agriculture started and more recently, for example, with bigger and bigger tractors in agriculture to have fewer drivers, a trend we also see in other industries,” he said. “It definitely opens up new opportunities for other jobs like developing and maintaining robots, drones, software and more.” Brad Buck

10 Spring 2019

Space Oddity Spaceflight changes brain pathways

rain scans of astronauts before and after spaceflight show changes to their white matter in areas that control movement and process sensory information, a University of Florida study shows. The deterioration was the same type you’d expect to see with aging, but happened over a much shorter period of time. The findings could help explain why some astronauts have balance and coordination problems after returning to Earth, said Rachael Seidler, a professor with UF’s College of Health and Human Performance. However, changes in one region — the cerebellum — were more pronounced for those whose missions were shorter, suggesting that our brains may be able to adapt given enough time. The study in JAMA Neurology, authored by Seidler and Postdoctoral Associate Jessica Lee of UF’s Department of Applied Physiology and Kinesiology in cooperation with NASA’s Johnson Space Center, evaluated scans of 15 NASA astronauts. The scans also showed the fluid around the brain pooling at the base of the cerebrum after spaceflight. The astronauts’ brains were essentially floating higher in their skulls after their time in microgravity. “We know that fluid shifts toward the head in space,” Seidler said. “When you see photos and video of astronauts, their faces often look puffy, because gravity isn’t pulling fluids down into the body.”

The same phenomenon could be drawing extra cerebrospinal fluid into their skulls, she said, which might contribute to a condition called Spaceflight Associated Neuro-Ocular Syndrome, which involves kinking of the optic nerve, visual changes and flattening of the back of the eye. “It could be slower fluid turnover, it could be pressure on the optic nerve or that the brain is sort of tugging on the optic nerve because it’s floating higher in the skull,” Seidler said. The balance issues caused by white-matter deterioration usually correct themselves after a few weeks back on Earth, but the brain changes that caused them might last longer. In future studies, Seidler and her colleagues plan to evaluate scans from six months after spaceflight to see how long the changes persist as well as what causes them and how they relate to vision changes and other post-flight health issues — key concerns for space tourism and extended space journeys such as missions to Mars. But there could be implications for those of us more likely to spend extended time on the couch than in a space capsule. The reason space affects astronauts’ balance back on Earth is that arms and legs unencumbered by gravity aren’t sending much sensory input to the brain, so the way brain pathways process information changes. “We have an increasingly sedentary lifestyle. It’s not the same as the effects on limbs

“We know that fluid shifts toward the head in space. When you see photos and video of astronauts, their faces often look puffy, because gravity isn’t pulling fluids down into the body.” — Rachael Seidler

in space, but if we’re laying around and not using our bodies, could the integrity of white matter pathways in the brain be affected?” she asked. “Another reason for an active lifestyle.” The study was supported by NASA and the National Space Biomedical Research Institute and conducted in

cooperation with colleagues from the University of Utah, University of Texas Health Science Center, Brigham and Women’s Hospital, Harvard Medical School and KBRwyle. Alisson Clark

By Cindy Spence

Photos

John Jernigan

12 Spring 2019

The

Researcher Within National Science Foundation Fellowships Nurture Young Scientists

ive or six years ago, David Mazyck taught an informal workshop to help students put together their applications for the prestigious National Science Foundation Graduate Research Fellowship. The fellowship is among the most generous funding for graduate students and gives them great freedom to conduct their research and find their footing in the world of the science academy. For 2019, the funding is $138,000 over three years, a sum that can be life-changing for a young researcher. All five students in Mazyck’s workshop won a fellowship. Mazyck says the most challenging part of mentoring these elite students is convincing them that reviewers want to know about them, not just their research. Mazyck’s experience is mirrored by anthropology Professor Connie Mulligan, who also mentors graduate students seeking the fellowship. “The students are so focused. That’s what a graduate student is supposed to be. They’re supposed to be obsessed with their research, right?” Mulligan says. “But your NSF Fellows, left to right: Andreana Cunningham, Holden Harris, Duy Nguyen, Shannon Brown, Ann Bernert, Rachel Narducci, Chris Clukay, Shar Siddiqui, Kim Ledger, Ryan St Laurent, Tiffanie Smith, Joshua Peeples, Adam Grossman, Julio César Pãchon, Robert Johnson, Brendan John, Rachel Atchison, John Calise

“We are far more diverse than we think we are. Humans move all over the place and carry different traditions, different languages, different genetic material.” — Andreana Cunningham

Andreana Cunningham Adviser: Valerie DeLeon Field of study: Biological Anthropology

research could change — and that’s fine — so, who are you as a researcher?” Today, Mazyck’s workshop is a class, open to all majors, and that question is key, he says. “Most experiments fail,” Mazyck says. “So how do you convince a reviewer that the unique experiences you’ve had on your educational journey will motivate you to get out of bed and go to the lab, even knowing you likely will fail? What is it that makes you think ‘I can do this?’ “That’s what reviewers want to know.” That can-do spirit shows in the 80 UF graduate students who have won the fellowship since 2013. NSF gets about 12,000 applications a year and accepts about 2,000. The students 14 Spring 2019

receive a stipend of $34,000 a year for three years, with additional support to the institution of $12,000 a year for three years. The fellowship’s purpose is to ensure the vitality and diversity of the science workforce for the United States. The group is impressive, says Judith Traveis, the Graduate School assistant dean for administration who oversees the fellowship. “When you hear what they’re doing, they all want to change the world,” Traveis says. But first, the fellowship changes them. “The fellowship really helped me take advantage of research opportunities,” says Andreana Cunningham, who works in anthropology Associate Professor Valerie DeLeon’s lab. “It has allowed me to embrace an interdisciplinary approach to my research. I’ve been able to venture outside my department and think in ways I don’t think I necessarily would have otherwise.” Cunningham is in the preliminary stages of her dissertation. She uses skeletal remains to study human diversity — historically and genetically — to challenge preconceived notions about identity and racial boundaries, both among groups of people and within groups of people. With her fellowship funding, she has been able to use the vast skeletal holdings of the Smithsonian Institution and this summer will travel to the Cleveland Museum of Natural History. “We are far more diverse than we think we are,” Cunningham says. “Humans move all over the place and carry different traditions, different languages, different genetic material.” In Mulligan’s lab in the Genetics Institute, Chris Clukay is working on two projects. In one, he has examined the genes related to stress response in Syrian refugee children who participated in a stress mitigation program. While the intervention helped everyone, his analysis showed that children with a

Holden Harris Advisers: Micheal Allen & William Patterson Field of study: Fisheries science; Marine ecology; Natural resource economics

“It makes sense to me that the best way to control a fishery is to develop it commercially. It’s a freemarket solution to managing an invasive species.”

certain genotype responded to the intervention a bit faster. In his other project, he is analyzing DNA expression in pregnant women in response to the ongoing civil war in the Democratic Republic of Congo. There is evidence that a baby’s DNA can be susceptible to the environmental stressors the mother experiences, so Clukay is also looking for markers of genetic changes in blood drawn from babies born to women in the war-torn region. Clukay says he’s not sure where his Ph.D. might take him but he is interested in both science policy and education. He enjoys teaching and with his chemistry and statistics background, often helps lab mates less versed in those fields. Although he started out in chemistry, he moved to anthropology because he wanted to do something to more directly help people. He says his favorite experience is watching someone who is struggling with a concept at the moment they catch on.

— Holden Harris

“You see the light in their eyes,” Clukay says. “I believe in making a difference.” He has seen that light as a martial arts instructor, too, and his martial arts expertise has come in handy in unexpected ways. Once, when ice formed around the seal of a minus-80 freezer, threatening the samples inside, Clukay took matters into his own hands. “I teach at a dojo, so I could see the weak points,” Clukay says. Three chops later, problem solved. Another innovative thinker is Holden Harris, who works with Micheal Allen and William Patterson in the Department of Fisheries and Aquatic Sciences. Harris, a former commercial spear fisherman, is investigating ways to take an invasive species, the lionfish, and develop it into a commercial fishery, both as a means of controlling its impact and using it as an economic resource. “It makes sense to me that the best way to control a fishery is to develop it

Chris Clukay Adviser: Connie J. Mulligan Field of study: Stress Genetics & Epigenetics

commercially,” Harris says. “It’s a freemarket solution to managing an invasive species.” Lionfish consume native reef fish that are important for grouper and snapper. When lionfish show up, native species decline. But lionfish are edible, and the price for lionfish is higher than the price for grouper and snapper, so developing a fishery may be a good way to control their population, Harris says. And in his own informal taste test, they got high marks. “We had a couple different species of snapper and lionfish, and lionfish was voted the best one,” says Harris, noting it was a different kind of peer review. “It was just me, cooking for friends.” Harris says the fellowship has allowed him to focus. “The fellowship says ‘your job here is to do this cool research.’ It’s validation,” Harris says. Mazyck remembers Harris in his class, and says, like other fellows, he pays it forward. Harris says he’s happy to help the fellows coming behind him — Duy Nguyen and Ann Bernert among them — reading their applications and helping them as he can. Although Harris is not in engineering, Mazyck did not hesitate to add him to the class. “I couldn’t help with his Ph.D. for a million dollars,” Mazyck says. “My role was to help him understand how his distance traveled matters to him as a researcher.” Mazyck says fellows come from all walks of life. He had one student who was almost embarrassed about his affluent background, but after getting to know him, Mazyck realized he was a gifted teacher. Another student, a superstar with a 4.0 GPA, had a normal childhood and went to college because it was expected. Mazyck discovered that she had a gift for mentoring. Many other students, about a third, are from impoverished backgrounds. 16 Spring 2019

Their parents are starting to do well, but for most of their life, their family has struggled. He gets to know all their unique experiences, often meeting outside the classroom. “I tell them to tell me about their childhood and their journey. What drives them? In engineering, we migrate here because of a passion for math and science but it goes beyond that,” Mazyck says. Mazyck tells the fellows to think about why their research matters to three people: a 12-year-old in Canada, a 12-year-old in Africa, and a 12-year-old in Syria, and ask themselves what they will do that will help those three people in their 20s. One young researcher said he wanted to make smaller satellites. Mazyck asked him, “Who cares?” The researcher responded that smaller satellites are cheaper, and again, Mazyck replied, “Who cares?” On the third try, the young researcher got to the heart of the issue: smaller, cheaper satellites will make it possible to disseminate knowledge worldwide. Mazyck says he often runs into his former NSF students on campus, which makes sense considering he has around 30 or 40 who have won or received an honorable mention. “I love seeing these students on campus,” Mazyck says. “NSF fellows all have smiles on their faces.” Recently, looking for mentors to help a new cohort of students, Mazyck reached out to his NSF grads. “I sent out an email,” Mazyck says, “and 18 responded within 30 seconds. “That’s what university life should be like.”

Fellows Since 2013, 80 UF graduate students have won the NSF fellowship. Here is a sampling of the fellows and their research.

Brendan John Adviser: Eakta Jain Field of study: Computer Graphics and Applied Perception

Related website: https://www.nsfgrfp.org/

Duy Nguyen Adviser: Xin Tang Field of study: Mechanobiology

Rachel Atchison Adviser: Andrea Lucky Field of study: Ant Community Ecology

Ann Bernert Adviser: Gilles Basset Field of study: Horticultural Sciences, Biochemistry

Shannon Brown Adviser: Blanka Sharma Field of study: Orthopedic Drug Delivery, Nanomaterials and Osteoarthritis

John Calise Adviser: Edward K.L. Chan Field of study: Oral Biology, Molecular and Cell Biology

Robert Johnson Adviser: Karen Bjorndal Field of study: Marine Biology

Kim Ledger Adviser: Samantha Wisely Field of study: Wildlife Ecology and Conservation

Julio César Pãchon Adviser: Susan Jacobson Field of study: Human Dimensions of Climate and Environmental Change

Rachel E. Narducci Adviser: Jonathan I. Bloch Field of study: Paleontology

Joshua Peeples Adviser: Alina Zare Field of study: Machine Learning

Shar Siddiqui Adviser: David Kaplan Field of study: Environmental Engineering

Tiffanie Smith Adviser: Juan Gilbert Field of study: Humancentered Computing

Ryan St Laurent Adviser: Akito Kawahara Field of study: Taxonomy, systematics and phylogenetics of moths

UF lab is focused on keeping honey bees healthy Photos by John Jernigan

By Cindy Spence

he honey bee is a keystone species, and without it, Jamie Ellis says, one out of every four or five bites you eat would disappear. “Twenty percent of my diet is not citrus, it’s not beef or dairy. It’s not poultry, wheat or corn,” says Ellis, the Gahan Endowed Professor of Entomology and leader of the University of Florida’s honey bee research program. “But 20 to 25 percent of what I eat comes from the efforts of honey bees.” Ellis says there are 20,000 species of bees on the planet. About 4,000 or so live in North America. There are 315 to 320 species of bees in Florida. Eight species of honey bees are confined to Asia. Just one species of honey bee has a foothold in the U.S. That makes the honey bee the workhorse of pollinating many food crops — watermelon, blueberries, strawberries, apples, almonds (especially almonds). And that makes Ellis and a team of honey bee research and extension scientists keenly focused on keeping the honey bee healthy.

18 Spring 2019

Native bees — bumblebees, sweat bees, carpenter bees and others — pollinate, too, but much of the work of pollinating crops, up to $20 billion worth nationally, is up to the honey bee, the only easily managed pollinator. The UF Honey Bee Research and Extension Laboratory has about 40 active research projects and is poised to ramp up research on several fronts after moving into a new home in August. The $4.5 million facility grew out of a groundswell of support from state beekeepers, from coins dropped in collection jars to a check for $500,000 from a hobbyist beekeeper. The facility — a bee campus of sorts — has a museum, a pavilion for outdoor teaching and meetings, an indoor classroom, labs, honey bee-themed artwork and an observation room with special lighting for bee-watching. And of course, bees, buzzing in and out of the trademark white boxes that house their hives.

Inside the Box Ellis has been a beekeeper since he was a boy and a bee scientist for decades, and even he says some of what goes on inside the hives is still a mystery. “Most of what we know about honey bees comes from our knowledge of these bees in white boxes, the managed hives,” Ellis says. “And people continue to discover things in the white boxes that we just didn’t know before.”

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One new discovery, by colleagues in Maryland with support from UF, is that Varroa mites are feeding on bee fat bodies. For 30 years or more, the bee world thought they were feeding on hemolymph, or bee blood. “The number one pest of honey bees has been feeding on something entirely different than that on which we believed it to be feeding,” says Ellis, who was a co-author on the paper in the Proceedings of the National Academy of Sciences. “This will change treatment strategies, and it explains a lot of Varroa’s impact on bee colonies.” Not long after Ellis arrived to take over the UF bee research and extension program in 2006, calls went out to save the bees. Colony collapse disorder had bees abandoning their hives in droves, with beekeepers losing up to 40 percent of their colonies.

Branden Stanford, lab manager, removes a frame of bees from a hive.

In the decade since, there’s been a boom in beekeeping, with new hives offsetting losses of old hives, staving off the “beepocalypse,” Ellis says. And a more nuanced view of the vulnerability of bees has emerged as well. Ellis uses the term colony losses these days to describe a host of ailments that threaten the viability of a hive, including mites,

20 Spring 2019

“Varroa is the cancer of the honey bee world. It is the honey bee world’s public enemy No. 1.” — Jamie Ellis

such as Varroa, bee nutrition, queen health and pesticides. Mites, especially Varroa, are a robust research arena for UF, with one doctoral student working on Varroa full time. “Varroa is the cancer of the honey bee world,” Ellis says. “It is the honey bee world’s public enemy No. 1.” Despite the attention, making progress on Varroa has been difficult. Honey bees are arthropods, but so are Varroa mites. Nearly all controls for Varroa are arthropodicides. “Using an arthropodicide to fight an arthropod inside an arthropod colony ... it’s not like killing a tick or a flea on a mammal,” Ellis says. “Killing an arthropod on an arthropod is remarkably tricky because it’s difficult to find new compounds that are active against Varroa but not the bee. And even if the compound isn’t lethal to the bee, it could have delayed, sub-lethal effects.”

Another complication is that Varroa must be collected from hives in order to study it in the lab. UF’s honey bee lab is working on in vitro or lab methods of rearing Varroa as a means of speeding up testing for treatments. “If we nail down that rearing method, we could look at novel ways of controlling them, for example, keeping them from reproducing,” Ellis says. “You can only do this work if you can physically watch Varroa in the lab through its rearing cycle.”

Well-Fed Bees Honey bee nutrition is an expanding area of investigation. There are two things bees need when they forage. When they go to a flower, they are either collecting nectar — a sugar water that flowers produce — or they are collecting pollen.

Varroa mites feed and reproduce on honey bee pupae, spreading pathogens to the developing bees.

Nectar becomes honey, and serves as fuel for the bees. “Honey is what moves the bee. When they consume honey, they’re getting carbohydrates that allow them to move their legs, beat their wings,” Ellis says. “It powers all the activity of a hive.” From the pollen, they make bee bread, which contains all the protein and other nutrients they need. It’s hard to imagine bees, flitting from flower to flower, not getting enough fuel or food, but Ellis says that happens. Honey bees are generalist foragers, meaning they collect nectar and pollen from a variety of flowers, without focusing on one species. But commercial honey bees don’t have a pollen smorgasbord. They may be served a feast of almond flowers, but it’s only almond flowers, and that unbalanced diet creates a nutritional deficit.

“Sometimes the bees simply run out of honey,” Ellis says. “The way you solve that is you feed them sugar water or corn syrup.” Sugar water solves the honey issue but the pollen issue is more complicated, because pollen is needed for the production of new bees, and new bees are necessary to keep pollination businesses booming. Bees will not rear offspring if they can’t collect pollen of a sufficient quality and bring it back to the hive. So, seasons matter. “We are in a pollen dearth right now,” Ellis said in December. To get a colony to produce offspring when it otherwise would not, beekeepers feed pollen supplements. The question, Ellis says, is do they work? Some pollen patties, he says, amount to “expensive poop.” “Just because it goes into the mouth doesn’t mean it is going into the system,” Ellis says. “It might be going straight through the bee.” Figuring out the value of pollen supplements is important, considering that 20 to 25 percent of managed bee colonies — about 650,000 — travel through Florida each year. Some overwinter in Florida as they prepare to head elsewhere to pollinate. For example, in January, the number one crop that needs pollination is almonds, mainly in California, so Florida bees are shipped west. The pollen supplements are particularly important in a pollen dearth, when bees are being asked to work overtime during their slow season. “Most honey bee colonies shut down in the winter months, essentially hibernating as it were,” Ellis says. “We’re trying to get bee colonies to be strong at a time of year they’re not ordinarily strong.” Better nourished bees might also mean healthier bees, with lower disease incidence. Ellis says the group is just beginning to look at how nutrition

affects tolerance to diseases and pests. So far in studies of pollen patties, the group has not noted an increase in the number of bees in fed colonies, which would be expected if the patties work. “Our bees are not only important for Florida crops,” Ellis says, “they’re important for the nation’s crops. “I can’t think of another ag commodity that is as important for the world as are honey bees.”

Pesticide Protection Pesticides also play a role in bee health, and to investigate bee exposure to chemicals the lab perfected a system to rear honey bees indoors to better observe the impacts of toxins. With its rearing system, the lab can take larva and rear them to adulthood in 21 days. Farmers need pesticides to protect their crops, but beekeepers need to know their bees are not hurt by those pesticides. Testing occurs on three levels, from lab conditions to field conditions, testing mortality after exposure to pesticides. For effective tests, both the exposed bees and the controls need to live to adulthood, but in earlier tests, not enough of the controls were surviving. With a test the lab developed, more than 90 percent of the controls live to adulthood, making for better comparisons between exposed and unexposed bees. The new method underwent an international test and 13 of 16 laboratories had 80 percent or greater survivorship of the control bees. The test, expected to become a model, has made it possible to do a wide range of toxicology tests in the past two or three years, including investigating sub-lethal impacts of pesticides on developing honey bees. “Bees can be treated with levels of pesticides we know they will survive, and then we can watch how their

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exposure affects parameters beyond just survivorship,” Ellis says. “It was a major, major breakthrough for us. We’re making the tests that exist more biologically relevant.” Honey bees are the most studied and highly managed bees, but there is a need to examine other bees, too, Ellis says. Over the years, the lab’s program on pollination ecology, which encompasses all bees, grew to the point that the UF Entomology and Nematology Department hired Assistant Professor Rachel Mallinger in 2017 just to focus on pollination ecology. The 315 or so other bee species in Florida, after all, are contributing to crop pollination as well. Bumblebees, for example, contribute to blueberry pollination, but just how much pollen they move is unknown. Sweat bees contribute to watermelon pollination. Unlike honey bees, many wild bees are solitary and nest alone rather than as a colony so little is known about where they nest and how they choose their nests. Little is known, too, about honey bee behavior in the wild. “We still have questions about what’s going on in the white boxes,” Ellis says. “If it’s a mystery what goes on in the white boxes, then it’s an enigma what goes on in a feral or wild colony.” Natural history questions have long gone unanswered with honey bees, Ellis says. When left alone, what do they do? How do they sort themselves out and at what densities? What are natural disease and pest pressures for unmanaged bees? Are some bee colony issues artifacts of the way bees are managed? Ellis thinks perhaps so.

species of bees on the planet

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foreleg

4,000 species live in North America

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species of honey bee in the U.S.

Feeding the Colony: Honey Bee Nutrition

Forager Bees ingest nectar

Nectar Carriers pass their load to Receiver Bees to store as honey

Bee Bread

Bee Boom The rising popularity of beekeeping heartens Ellis but doesn’t surprise him. For an animal that stings, bees are nevertheless charismatic, and they fit

compound eye

Forager Bees collect pollen

Source: G.A. Wright et al/; AR Entomology, 2018.

Pollen Collectors pack pollen into cells to form bee bread

head

Digital Database of Bee Wings used for Identification

antenna

simple eye (ocelli)

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UF is working to develop an international morphometric database that allows for identification of bees based on photographs of their wings and other body parts.

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Egg (Day 0 to 3)

Larva (Day 4 to 10)

Honey Forager Bee

Life Cycle of the Honey Bee Pupa (Day 11 to 20)

Nurse Bee Capped Pupal Cell (Day 11 to 20) New Adult (Day 21)

â&#x20AC;&#x192;â&#x20AC;&#x160; 23

K. Kinsley-Momberger

Nurse bees consume bee bread in order to produce the food they feed to larval honey bees.

the urban farming moment society is in just now. More and more, people are adding bees to their chickens and blueberries and raised beds of veggies. The public took to heart the pollination message in campaigns to save the bees and keep fruits, nuts and vegetables in supermarkets. In 2006, there were 1,100 beekeepers registered in Florida. Today, there are almost 5,000. While hobbyists outnumber commercial beekeepers, commercial operations manage 92 percent of honey bees in Florida. Beekeeping classes, too, are increasingly popular, so much so that the Department of Entomology and Nematology just hired Lecturer Cameron Jack to focus on it full time. Each fall and spring semester, the course draws about 120 students and about 60 in the summer. Ellis says Jack is developing a certificate program, with multiple courses related to beekeeping. “We’ll have something no other university has,” Ellis says. “You can go to almost any other land grant and get a course on bees. We’ve already got two, but we’re shooting for six, seven, eight.”

With the new lab and new positions, Ellis says he’d like to see the bee campus become a bee center, a “onestop shop for research, extension and instruction.” “We’re getting there,” Ellis says. “We now have the facility to support that.” Ellis says the public-private collaboration that funded the center astounded him. A group of beekeepers approached him five or six years ago and wanted to help him buy lab equipment. “I said, ‘Look guys, you can buy it but I have nowhere to put it,’” Ellis says. As a joke, he suggested, “Go get a lab.” “Everybody and their brother in the Florida bee world was raising money.” The new 16,000-square-foot facility, Ellis says, will amplify the lab’s research, instruction and extension efforts, and that was the goal of the bee community, says David Mendes, a Fort Myers beekeeper who wrote a check for $200,000 to kick off the fundraising. “Nothing like this exists anywhere else in the country,” Mendes says. “Florida is a particularly good area to raise bees. The climate helps, of course,

but a lot of it is because of Jamie himself. In Florida, beekeeping and research go hand in hand.”

Bee Keeper Ellis grew up in rural east-central Georgia and barely remembers when bees weren’t a part of his life. In a hazy memory, he recalls being about 6 when someone came to his school to give a demonstration about bees. The speaker gave out brochures, and the brochure ended up in his toy box. At 8, he tried to convince his parents to get him bees, with no luck. But he was hooked and kept reading about bees. In sixth grade, at age 12, he ended up talking with his teacher about bees, bemoaning his beelessness. The teacher’s uncle, it turned out, was a beekeeper. “She said, ‘If I get you an empty beehive, will you promise to fill it?’” Ellis recalls. A few weeks later, “she showed up at our house with a beehive.” Ellis’ parents, backed into a corner, got him bees from a local beekeeper.

The bee observation room is bathed in red light. Bees cannot see red, so the light allows observers to see the bees without affecting the bee’s behavior. Bees enter the observation room hives (far right) through a small entrance in the wall of the lab. A colored dot on the back of a bee, middle photo, identifies which hive it came from, helping researchers study drift between colonies.

24 Spring 2019

“We’ll have something no other university has. You can go to almost any other land grant and get a course on bees. We’ve already got two, but we’re shooting for six, seven, eight.” — Jamie Ellis When the beekeeping mentor died a year later, Ellis became the owner of 15 more hives at the age of 13 and managed his bees at his grandfather’s dairy farm. Bees were part of every science fair and 4-H project, and when he went to college at the University of Georgia, he was close enough to home to keep his bees. At Georgia, he worked in a bee lab much like the one he joined at UF in 2006, but fully intended to go to medical school. He figured that’s what kids who liked science did. His course corrected when his mentor took him aside. “He said, ‘Look Jamie, it’s clear you like bees and you like research. You know that bee science is what you’re supposed to do,’” Ellis says. Today, Ellis keeps bees in his backyard. He says he is one of the few bee scientists who also is a beekeeper. The rewards are professional, but personal, too. “I’ve always been happy around bees.” Jamie Ellis Gahan Endowed Professor of Entomology and Nematology jdellis@ufl.edu Related website: http://entnemdept.ufl.edu/honey-bee/

Jamie Ellis, outside the new lab, which features honeycomb-shaped structures on the front windows.

When Less Oxygen

HE LS Putting Novel Spinal Cord Injury Therapy To The Test

By Michelle Koidin Jaffee 26â&#x20AC;&#x192; Spring 2019

Photos by Jesse S. Jones

“

uperman” actor and disabilities activist Christopher Reeve often traveled the country to visit teams of neuroscientists working to discover possible treatments for spinal cord injuries. A framed photo of Reeve during one such visit — in his wheelchair with his portable ventilator, the result of a horseback-riding accident — sits prominently today in the office of Gordon Mitchell, a pioneering researcher known internationally for his innovative studies concerning how to strengthen breathing and other movements among those with severe spinal cord injuries.

The photo of the late movie starturned-activist serves as inspiration to Mitchell, who came to the Evelyn F. and William L. McKnight Brain Institute and the Department of Physical Therapy at the University of Florida from the University of Wisconsin at the end of 2014 to found UF’s Center for Respiratory Research and Rehabilitation and advance efforts to develop therapies for one of medicine’s most vexing conditions. “I once saw Christopher Reeve speak, and during his talk, he expressed that his greatest fear was that the power would go out — and that would mean the ventilator that sustained his life would stop,” said Mitchell, professor of neuroscience in UF’s College of Public Health and Health Professions. So, while the inability to walk may be the most visible sign of a spinal cord injury, for those most severely injured, it is the inability to breathe on one’s own that poses the gravest danger and creates the most fear. “For people with chronic spinal cord injury, the No. 1 cause of death is respiratory failure,” Mitchell said. “For people who have suffered these catastrophic injuries, once they’ve had all the benefits that conventional rehabilitation has to offer, there is little hope of further improvement. So what we need are new strategies — and we think we may have found one.”

This promising new strategy is called “therapeutic intermittent hypoxia.” Hypoxia is a word that makes some people brace. Defined as “a deficiency of oxygen reaching the tissues of the body,” hypoxia can be quite harmful if taken to the extreme. Intermittent periods of hypoxia are one major consequence of sleep apnea, which contributes to high blood pressure, diabetes — even cancer growth. In the worst cases, hypoxia can be fatal. But what Mitchell has discovered is that modest intermittent hypoxia holds hidden benefits. He has developed a technique that involves breathing a lower level of oxygen in short, repeated

bursts for a limited period to strengthen breathing ability. One remarkable surprise, Mitchell said, is that it also strengthens other movements, including walking and grasping. Mitchell is gaining confidence in the possibilities of this technique. Over more than two decades of research — including very basic molecular studies in rats and advancing in recent years to human clinical trials at collaborating institutions — he and his team have demonstrated that this technique shows promise as a potential therapy to improve breathing and other movements in people with chronic incomplete spinal cord injury, including those with quadriplegia, or paralysis from the neck down. This discovery could also have implications for many other clinical disorders that compromise the ability to breathe or move, including amyotrophic lateral sclerosis, or ALS, multiple sclerosis, post-polio syndrome, stroke and traumatic brain injury. It holds the promise of a potential low-cost, noninvasive therapy to build strength in multiple ways.

Physical therapist Kate Cavka places a mask over a participant’s mouth and nose to alternate giving low-oxygen air followed by normal air while sensors measure the core muscles that contribute to breathing.

Gordon Mitchell and Emily Fox are using a $2.4 million grant to test therapeutic intermittent hypoxia in spinal cord injury patients.

“For people with chronic spinal cord injury, the No. 1 cause of death is respiratory failure … So what we need are new strategies — and we think we may have found one.” — Gordon Mitchell “The work we’re doing is really focused on helping those with spinal cord injuries to regain movements: Those movements would be breathing, arm movements like grasping, and it might even be standing up or walking,” Mitchell said. Monica Perez, of the Miami Project to Cure Paralysis, said while there’s still much to be learned about how intermittent hypoxia works in humans, preliminary data suggest the technique could be a significant advancement in the recovery from spinal cord injury. “Dr. Mitchell is a world expert in the field of respiratory biology and the use of intermittent hypoxia,” said Perez, a professor in the Department of Neurological Surgery at the University of Miami and a collaborator of Mitchell’s. “What’s interesting about intermittent hypoxia is it’s a noninvasive technique that is easy to use and has shown to be effective in improving voluntary motor output.” 28 Spring 2019

Now, Mitchell and co-principal investigator Emily Fox, are launching UF’s first human clinical trial to test their hypothesis that intermittent hypoxia improves breathing ability.

Neural Plasticity Under a new $2.4 million grant from the U.S. Department of Defense, Fox and Mitchell will test therapeutic intermittent hypoxia over four years in about 55 people with chronic spinal cord injuries in a collaboration between UF and Brooks Rehabilitation in Jacksonville. The clinical trial will be carried out at the Brooks Rehabilitation Clinical Research Center. “We are testing our hypothesis that a combined approach of breathing low oxygen and conventional respiratory strength-training exercises will be better than either strategy alone,” said Fox, a research assistant professor in UF’s Department of Physical Therapy in the UF College of Public Health and Health Professions and a clinical research scientist at Brooks Rehabilitation. “Our hypothesis is that when we combine these strategies, it’ll have the most beneficial effect.” Using sensors attached to the skin to measure activity in the core muscles that contribute to breathing and additional sensors that measure blood oxygen levels and the amount and force of air being inhaled and exhaled, the research team will place a mask over a participant’s mouth and nose to alternate giving low-oxygen air (9 percent oxygen) for a

minute, followed by normal room air (21 percent oxygen) for a minute, about 15 times in all. “Then the participant will have a rest period to allow the treatment effects to take place,” Fox said. “After we wait about 45 minutes, we do those tests again, testing the breathing function and core muscle function again. We also test the ability to sit up and to stand, because the effects of intermittent hypoxia can be profound and affect other motor functions.” Mitchell explained the science behind the treatment: “After years of work, we came to realize that repeated exposure to low oxygen — just slight decreases in oxygen — triggered events in the brain and spinal cord that lead to what we call ‘neural plasticity,’” he said. “It’s basically like turning up the volume on a stereo so you can hear the signal more. This, we realized, could be very useful in restoring breathing after spinal cord injury in the cervical region of the neck or in a lot of neurodegenerative diseases, all of which end life because of failure to breathe adequately.” For the participant, the difference between breathing 21 percent oxygen and 9 percent oxygen for one minute is so subtle, Fox said, that most people are unable to reliably report whether they were breathing normal air or lowoxygen air. In current research efforts, the machine that provides the oxygenreduced air is similar to those used by mountain climbers and endurance athletes who are training to compete in high-altitude environments. But as intermittent hypoxia research is taken to the next level, Mitchell is collaborating with engineers, including Neil Euliano of Convergent Engineering in Gainesville, to develop a standardized device specific to this use. “When we expose the subjects to the

low oxygen, it’s a level of oxygen that’s about the same as if they had climbed Denali, which is the highest peak in North America,” Mitchell said. “But on the other hand, they never really get there. It’s a journey that lasts one minute, and at the end of that minute, we return them to Gainesville.” Mitchell warns against any patients attempting this technique at home, as for now it remains experimental — and could be harmful if unmonitored by professional treatment providers. Dosages, frequency and duration are the focus of multiple ongoing studies. Furthermore, the ultimate safety and lasting benefits of intermittent hypoxia as a treatment have yet to be proven. The benefits appear to be temporary and to last from a number of hours to a number of weeks. Like exercise, the treatment most likely would need to be repeated regularly to maintain its benefits.

Sensory Watchdogs Intermittent hypoxia works, Mitchell said, because it prompts the body to adapt to repeated changes in oxygen levels. When the level of oxygen reaching the tissues drops, the body has “watchdogs” that respond, he explained. These so-called watchdogs “are sensory neurons in your neck called the carotid body chemoreceptors, and when oxygen goes low — for even a very brief period — they are activated and tell your brain that something important is changing,” he said. This increases the activity of a kind of neuron in the brain that contains the neurochemical serotonin, and the neurons “broadcast” across the brain and spinal cord. “When they release serotonin, it triggers changes that we refer to as plasticity,” Mitchell said. “The plasticity is in motor nerve cells that innervate the muscle. So what

“We are testing our hypothesis that a combined approach of breathing low oxygen and conventional respiratory strengthtraining exercises will be better than either strategy alone.” — Emily Fox happens is that plasticity makes them work better.” The key is to activate the carotid body chemoreceptors and the neurons that contain serotonin while minimizing the amount of hypoxia in tissues throughout the body. By shortening the episodes of hypoxia, researchers are able to accomplish this goal. Once serotonin has worked its magic by triggering neuroplasticity, the motor nerve cells are more active, causing the diaphragm to make stronger contractions — making each breath deeper. After two decades of basic research on rodent models in an effort to understand this process and why it might work, Mitchell’s team started to translate their findings to humans in 2010, with clinical trials at partner institutions Emory University and the Rehabilitation Institute of Chicago. Thus far, Mitchell’s team and collaborators have published seven articles in high-profile journals indicating they can produce changes in limb movements. Because of greater difficulties working with ventilator-dependent patients, they began studies in those with lesssevere injuries that impact walking and arm use. Now, they are turning their efforts to improving breathing in people with chronic spinal cord injuries. 29

THERAPEUTIC INTE Y IVIT CT

Flat Diaphragm

The initial studies demonstrated an increase in leg strength and substantial improvement in walking ability in patients who had no prognosis for functional gains. These were followed up with a preliminary study demonstrating improved hand function in people with quadriplegia, like Christopher Reeve had. But more research is needed before intermittent hypoxia could become a clinical treatment. “Eventually there will need to be a full-scale clinical trial involving multiple sites. Only after we understand the outcome of that trial, we’ll be able to really say this is a clinical treatment,” Mitchell said. In the meantime, there is much work to be done to prepare for that comprehensive clinical trial.

International Consortium Traditional goals of spinal cord injury research have focused on restoring the ability to walk. But to Mitchell, the goal has always been restoring critical yet perhaps under-appreciated 30 Spring 2019

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“As clinicians, we want to have as many tools in our toolbox as possible to maximize the number of interventions we’re performing in therapy.” — Kate Cavka automatic functions like breathing. Mitchell first became captivated by the process of breathing while studying diving mammals and marine biology as an undergraduate at the University of California, Irvine. He happened upon a comparative respiratory physiology lab, where he discovered a passion for understanding how animals control their breathing. Today, Mitchell has taken that early interest and become a worldwide leader, forming an international therapeutic intermittent hypoxia consortium to accelerate progress and hosting a first-ever retreat that brought 130 researchers to Gainesville from as far away as Australia, France and the Ukraine.

He has positioned UF for prominence in this field by bringing together researchers from UF and Brooks Rehabilitation, and by collaborating — rather than competing — with colleagues at other institutions who have multiple different studies now underway. “What Dr. Mitchell has done is tremendously important because he brings people with different areas of expertise together to address different aspects of a central question,” said Perez, of the Miami Project to Cure Paralysis. “Since we all have different areas of expertise, we all help each other. Our role (at Miami) is to help understand the effects of acute intermittent hypoxia in the human central nervous system — what are the

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mechanisms that contribute to those improvements in performance.” Dr. Zev Rymer, a professor at Northwestern University and director of Research Planning Engineering in Neuroscience at the Shirley Ryan AbilityLab, said his lab relies heavily on the work of Mitchell and that of his team to drive their clinical work. “We have been using the basic information Gordon provided from animal models and extending that into humans, not just in breathing but in how intermittent hypoxia might affect other parts of the body,” said Rymer, whose lab recently launched two major clinical trials testing intermittent hypoxia in humans. “The protocols we use and the basic science that motivated us came from Gordon’s work.”

Hope for the Future As a physical therapist at Brooks Rehabilitation, Kate Cavka sees patients with spinal cord injuries in an outpatient facility, shortly after they’ve returned home from the hospital.

“They’re just getting home and realizing what their new world looks like at that moment in time,” Cavka said. “Generally, there’s a lot of anxiety.” She helps patients to set new, realistic, incremental goals. One aspect of treatment might be focused on walking again, but Cavka also highlights the importance of respiratory function, such as coughing: Muscle strength to keep the airway clear is essential to prevent pneumonia. Assisting with the intermittent hypoxia research gives Cavka a sense of hope. “As clinicians, we want to have as many tools in our toolbox as possible to maximize the number of interventions we’re performing in therapy, so we can achieve more: more functional capacity, more independence, better quality of life,” she said. One patient, 21-year-old college student Francois Fried, was left in a wheelchair from a dirt-bike racing accident in November 2016. While he has built core strength and improved

his ability to move around through fiveday-a-week physical therapy sessions, he feels his progress has begun to plateau. During a recent therapy session, Fried said he was intrigued by the possibilities of intermittent hypoxia. “I hope they do a long-term study and see if we can get really good results out of it,” he said. Like Fried, many who have spinal cord injuries suffered them at a young age, with a whole life ahead of them. “What we think is really important,” said Mitchell, “is if this does work, it offers hope to individuals that have suffered so very long.” As time passes post-injury, hope tends to dwindle. “We hope,” he said, “to give that hope back.” Gordon Mitchell Professor of Neuroscience gsmitche@phhp.ufl.edu Emily Fox Research Assistant Professor ejfox@phhp.ufl.edu

resources from the National Science Foundation to transport about a million pounds of equipment and dozens of people to this desolate location just 600 kilometers from the South Pole. An advance crew driving giant tractors — with groundpenetrating radar arrays stretched in front of them to detect dangerous crevasses in the ice — had spent almost two weeks hauling most of the drilling and scientific equipment and provisions 900 kilometers across the ice on skis from the U.S. base at McMurdo Station. They carved a runway into the snow that enabled a specially equipped C-130 transport plane on skis to bring several dozen more scientists, students and logistical support people, and many more boxes of supplies to the site. The researchers erected a tent city on the frozen plain and then went to work, 24 hours a day in shifts. The varying needs of the scientists on the project — geologists, ecologists, biologists, chemists — dictated the order of the instruments that went down, and hopefully came back up, the hole, says Christner, an associate professor of microbiology and cell science in UF’s Institute of Food and Agricultural Sciences. “You want to sample the water column before you put a core into the bottom of the lake that’s going to stir up all these sediments,” Christner says, adding that there’s another reason the By Joseph K ays researchers get water samples before sending the long, heavy sediment corer down the borehole. tanding in the perpetual sunshine and chill of the “The sediment core is a big beast and the riskiest thing that Antarctic summer last Dec. 26, UF microbiologist we put into the borehole, because if it gets stuck, that’s the Brent Christner peered into a hole 60 centimeters in end of the season,” Christner says. “Those first water samples diameter in the ice below his feet. may be the only water samples we get. Every milliliter of that Years of planning and preparation, millions of dollars and first water is accounted for, so if we didn’t get another sample 60 hours of boring with hot water through more than 1,000 there are four or five major science objectives that we could meters of ice had finally opened a window into Lake Mercer, a still meet.” body of water twice the size of Manhattan that hadn’t seen the But the team that operates the drilling equipment had done light of day in at least thousands and perhaps millions of years. their work well, and the borehole provided excellent access to Now, Christner and his colleagues on the Subglacial Antarcthe lake far below. tic Lakes Scientific Access, or SALSA, team had just a few days Over the next 10 days, Christner, UF doctoral student to conduct a carefully choreographed series of experiments to Christina Davis and the other scientists carefully extracted extract as much information as possible from the lake’s water all manner of samples from the lake, analyzing some in the and sediment before the borehole froze again. 40-foot-long shipping container lab on site and prepping many As a co-principal investigator on the SALSA project, more for further analysis back at McMurdo Station or in Christner had spent years helping to marshal funding and Gainesville.

Drilling Down L ake beneath Antarctic ice reveals its secrets

Billy Collins

Looking down the borehole that extends more than a kilometer through the Antarctic ice to Lake Mercer. A collar of ultraviolet lights surrounds the opening to prevent any sources of contamination being introduced into the lake.

Dynamic Ecosystem The SALSA website describes the Antarctic subglacial environment as “a dynamic ecosystem where life, ice, water, and rock form a web of complex interactions.” SALSA is employing “an integrated approach of scientific discovery that samples from three geobiological systems” — hydrology, geology and geomicrobiology — to “learn new information about our planet’s past and gain knowledge on subglacial processes such as carbon cycling and water-ice dynamics.” “Liquid water has been known to occur beneath the Antarctic ice sheet for more than 40 years, but only recently have these subglacial aqueous environments been recognized as microbial ecosystems that may influence biogeochemical transformations on a global scale,” Christner and his colleagues wrote in Nature in 2014 after an expedition to subglacial Lake Whillans, a smaller lake about 75 kilometers from Lake Mercer. Scientists have good evidence that there are active hydrological processes beneath the ice streams in this region, which they described in the 2014 Nature paper as “a network of three reservoirs … that regulate water transport to a subglacial estuary at the grounding zone, linking the hydrologic system to the sub-ice-ocean cavity beneath the Ross Ice Shelf.” The Ross Ice Shelf — the world’s largest floating ice shelf at about the size of France — holds back even more ice in land-based glaciers, so anything that might contribute to its instability is cause for concern. “That part of the ocean, like any part of the ocean that is in a coastal region, is affected by runoff from the land,” Christner says. “But here, all that export of nutrients from the continent occurs underneath the ice, so the question 34 Spring 2019

remains as to how that actually influences the biological and chemical oceanographic system around Antarctica.” Christner says that by analyzing the water and sediments cored from the bed of Lake Mercer, scientists can get a better idea of what kinds of biological processes are going on now and go back through time to understand the history of the region. “For example, when was the last time this area was inundated — was it a 100,000 years ago, was it a million years ago?” Christner asks. “That is something that is of great interest for understanding how the dynamics of the West Antarctic ice sheet behave under rising sea levels and temperatures.” That’s just one of the reasons Christner and his colleagues are seeking to understand what kind of life exists in

these subglacial lakes. The 2014 Nature paper, on which Christner was the first author, was the first to confirm that “aquatic environments beneath the Antarctic ice sheet support viable microbial ecosystems.” The water in Lake Whillans was rich in organic compounds, probably released from fossils buried in the lake bed millions of years ago when the area was open ocean. Those compounds supported a dense and varied bacterial life in the lake, with nearly 4,000 species and 130,000 cells per milliters, according to the Nature paper. At Lake Mercer, Christner, Davis and their colleagues focused on gathering samples to confirm those earlier findings about bacteria and determine whether any higher life forms survive in the cold, dark environment.

“What is the essence of Antarctica is covered by ice that is an average of two kilometers thick. Up to a decade or so ago, scientists thought it wasn’t a place where life could exist, but this research clearly shows that life is abundant beneath the ice in Antarctica. It’s the biggest wetland on our planet.” — Brent Christner

ill

= th ep d Ice 00m 1,1

de ke La 15m 10 A microorganism collected in 2013 from Lake Whillans

Christner says that because the window to gather samples from Lake Mercer was so small, scientists didn’t waste anything that came up through the borehole, whether it was mud on the bottom of an instrument to measure the water column or samples in a device Christner designed to filter lake water through three progressively finer screens, from 3 microns down to 0.2 microns. In some of that mud the team made a surprising discovery — what looked like remains of crustaceans. But even after further analysis at McMurdo Station, it was unclear how long the creatures had been dead or where they came from. Based on those initial observations, however, Christner and Davis decided to get one more water sample with just the largest filter in place to only capture larger creatures.

“We wanted to see if we could actually find anything more complex than a microbe,” Christner says. “We looked hard at that filter and we didn’t see anything like they found in the mud, so we put the samples in a tube and we froze them and we’ll analyze them more closely when they get back to our lab.” Davis is particularly focused on messenger RNA, because the presence of the short-lived genetic material can help distinguish between creatures that are living in the lake today and ones that died thousands of years ago. “DNA can be preserved for a very long time, so that could be dead or dormant organisms, but mRNA breaks down super quickly so the presence of mRNA tells you something,” Davis says. Davis spent the latter part of her journey stabilizing and packing hundreds

A cylindrical submersible is lowered through the hole and relays video signals to the surface. Source: Tristy Vick-Majors/SALSA; M.R. Siegfried & H.A. Fricker.

of samples for shipping to Gainesville, where she and Christner will use stateof-the-art microbiology tools, like nucleic acid sequencing and bioinformatics analysis to tease out the how the ecosystem functions in the cold, dark lake. That knowledge will not only inform how systems work on Earth, it might also help planetary scientists plan exploration of extraterrestrial bodies, like Europa, the water-covered moon of Jupiter. “This is not even close to the conditions on a place like Europa,” says Christner, who is also involved in 35

pt h

Brent Christner Associate Professor of Microbiology and Cell Sciences xner@ufl.edu

Billy Collins

Related website: http://www.brent.xner.net/ https://salsa-antarctica.org/

36 Spring 2019

Brent Christner

planning for a future NASA mission to the Jovian moon. “But when you’re looking at a system like Europa and you’re trying to understand what could live there, it’s the closest thing that we have on Earth — something that’s under kilometers of ice, isolated from inputs from the surface, isolated from the possibility of photosynthetic activity.” Christner says he’s fascinated by how far polar science has come in just the last few decades. “Even though people have been doing biology in Antarctica for over 100 years, really most of the continent — and it’s about the same surface area as Russia — was believed to have very little life,” he says. “In just a few decades, we’ve seen that transform. What is the essence of Antarctica is covered by ice that is an average of two kilometers thick. Up to a decade or so ago, scientists thought it wasn’t a place where life could exist, but this research clearly shows that life is abundant beneath the ice in Antarctica. It’s the biggest wetland on our planet.”

Extreme Environment Christina Davis is known as the adventurer in her family, but even she held back about her plans to spend several weeks in Antarctica. “I couldn’t tell my grandma right away,” the Iowa native says with a chuckle. “We’re farmers, we worry. And it is a harsh continent, so I had to promise I was going to be very careful.” A 16-hour commercial flight from Chicago to Christchurch, New Zealand, was only the first leg of her journey to bottom of the world. Then it was another eight hours to the U.S. base at McMurdo Station, Antarctica, and another 2-hour flight on a C-130 military transport equipped with skis to the research site 600 kilometers from the South Pole. There she joined about 50 other scientists and support personnel on

Billy Collins

“I think this project picked me. I like astrobiology, or life on other planets, and understanding how life can occur in extreme environments. I enjoy exploring how organisms can survive in these climates and the adaptations it takes to live there.” — Christina Davis the SALSA project to study Mercer Subglacial Lake. Three years into her Ph.D., Davis worried that if the drilling didn’t go as planned she might have to come up with another project, but “we were all very surprised at how smoothly things went. When we got through to the ice, it was like ‘OK, game time. Here’s our schedule, let’s get to it.’” Over the next two weeks, the researchers extracted enough samples “for several dissertations,” Davis says, and she expects multiple scientific papers to come from the results. Davis says her small tent pitched on the Antarctic ice was surprisingly comfortable, but she admits that she was usually so tired by the time she got back to it that sleep wasn’t hard to find, even with the sun shining down 24/7. “24-hour sun is hard to get used

to, but I had lots of 20-hour days in the lab, so then it doesn’t matter about the cold or the sun, you’re just going to pass out,” she says. “I would go back and crash and then wake up and start again.” Davis was first introduced to microbiology in high school when she worked in a lab at Dupont Pioneer in Johnston, Iowa, where her mother is an entomologist and her father is a biochemist. “I had an amazing mentor who taught me all about genetics and microbiology,” she says. “I worked on putting different plasmids into corn and soybeans, so that was my first taste of what bacteria are capable of.” After earning a bachelor’s degree in microbiology and genetics from Iowa State University, she chose to go directly to a doctorate and arrived at the University of Florida just as Brent Christner was

arriving at UF from Louisiana State University. “I got to help set up his lab, buy all the equipment, so that was a very beneficial experience if I do decide to go into academia because those are things you’re going to have to know how to do,” she says. Davis says her experiences working in Christner’s lab have prepared her well for whatever direction she takes in her career, whether it’s in academia or as a scientist with an agency like NASA or NOAA. “I think this project picked me,” Davis says. “I like astrobiology, or life on other planets, and understanding how life can occur in extreme environments. I enjoy exploring how organisms can survive in these climates and the adaptations it takes to live there.”

Creating the World to Come By Alisson Clark Photos

Brianne Lehan

and

Lyon Duong

Science And Art In The Anthropocene

ANGÉLICA ALMEYDA ZAMBRANO

The World to Come: Art in the Age of the Anthropocene explores an era of rapid, radical and irrevocable ecological change through works of art by 45 international contemporary artists. Organized by Harn Museum Curator of Contemporary Art Kerry Oliver-Smith, the exhibition examines the fate of the planet through more than 65 works of photography, film, sculpture and mixed media. While geological epochs are known as products of slow change, the Anthropocene has been characterized by speed. Runaway climate change, rising water, surging population, nonstop extinction and expanding technologies compress our breathless sense of space and time. Human impact has created a profound and disastrous effect on the Earth. Artists in the exhibition respond by upending the status quo, challenging human mastery over nature and attuning us to the deep bond between human and nonhuman life. The World to Come unfolds around seven overlapping themes: “Deluge,” “Raw Material,” “Consumption,” “Extinction,” “Symbiosis and Multispecies,” “Justice” and “Imaginary Futures.” Topics range from disaster, environmental devastation and loss to the emergence of new bonds and alliances between humans and nonhumans. Also considered is the magnitude of waste and growing populations, the laws of nature, inequality and protest. Lastly, artists explore the effects of technology and make a call for optimism with new ways of imagining a vibrant future for the world to come. After debuting at the Harn Museum in September 2018, the exhibition opens at the University of Michigan Museum of Art in April. 38 38 Spring Spring 2019 2019

DAVID PREVATT

BRENT REYNOLDS and MADAN OLI “WE CAN HAVE CONSERVATION AND DEVELOPMENT IN THE AMAZON.” Angélica Almeyda Zambrano, Assistant Professor of Tourism, Recreation & Sport Management, College of Health and Human Performance As co-director of the GatorEye Unmanned Flying Laboratory, Almeyda Zambrano is helping sustainable tourism gain ground as an alternative to deforestation. She’s pioneering datagathering via 3D drone scans in the Amazon and other key conservation areas. “Typically, I would ask people about their forest and rely on those answers. But if I can quickly fly over it, I can get gigabytes of data on the quality of that forest — for example, how much carbon is it sequestering, or the area of secondary vs. old-growth forest,” she says. “My next step is to compare how ecotourism can result in environmental and social win-wins.” “Paradise on Fire” Series, by UF College of the Arts Professor Sergio Vega, 2007, courtesy of the artist

“WHAT CAN ONCOLOGY LEARN FROM ECOLOGY?” Reynolds, Professor of Neurosurgery, UF Health Brent Madan Oli, Professor of Wildlife Ecology and Conservation, UF/IFAS Can wisdom from wildlife help us outsmart cancer? That’s what the 10-year collaboration between Reynolds, a neuroscientist, and Oli, an ecologist, asks — and answers. Together, they launched a discipline called eco-oncology, applying what we know about animal populations to tumor cells, which communicate, migrate and reproduce much as wildlife does. One lesson: When managing a pest plaguing a crop, it’s rarely beneficial to try to defeat it completely. That approach can leave behind only the hardiest invaders, which come back even stronger. The same is true for tumors. Instead of pummeling them until only the strongest tumor cells remain, could we manage the population, keeping the toughest ones in check? Lessons like these could reshape our approach to cancer treatment. “Caribou Migration” by Subhankar Banerjee, 2002, loan courtesy of Hood Museum of Art, Dartmouth College, Hanover, New Hampshire; purchased through the Charles F. Venrick 1936 Fund

“YOUR HOME IS YOUR CASTLE, AND CASTLES AREN’T BLOWN DOWN BY WIND.” David Prevatt, Associate Professor of Civil and Coastal Engineering, Herbert Wertheim College of Engineering Knowing how to protect homes from wind damage doesn’t help if homeowners don’t act on it. Prevatt looks at ways to take engineering knowledge to the public to safeguard life and property. “We have to make a long-term commitment to sustainable construction,” he says. “The houses we build today will affect the vulnerability of our community for the next 50 to 70 years. As civil engineers, it is our responsibility to ensure you can find the construction technology so you won’t have to live with the uncertainty that the next hurricane is going to blow your house away.” “Untitled,” 2015, by Sandra Cinto, 2015, courtesy of the artist and Tanya Bonakdar Gallery, New York 39

ZOLISWA “ZOE” NHLEKO “WE WILL GET THIS RIGHT.” Zoliswa “Zoe” Nhleko, Doctoral Candidate in Wildlife Ecology and Conservation, Institute of Food and Agricultural Sciences A junior scientist with South African National Parks, Nhleko studies how stress from poaching affects white rhinos. One question is how they choose their habitat. It’s not clear why they prefer the southern part of Kruger National Park: “It’s like there is a line they will not cross. Once we understand what they are looking for, then we may be able to move them from high-poaching areas into suitable habitats in safer areas,” she says. “We could manipulate the environment and make it unsuitable in a way that gets them out of danger, because by themselves, they’re not doing it. They’re not scared of people, but they should be.” “White Rhino, Namibia,” by Maroesjka Lavigne from the series Land of Nothingness, 2015, courtesy of Robert Mann Gallery, New York

“WE’RE NOT JUST HERE TO DABBLE AROUND. WE’RE HERE TO ANSWER QUESTIONS.” Christine Angelini, Assistant Professor of Environmental Engineering Sciences, Herbert Wertheim College of Engineering Angelini works to understand and restore resilient coastal ecosystems, which can protect us from storms and algae blooms and support fishing and tourism. “I’ve been working a lot more with managers here in Florida that are on the ground doing restoration activities. I almost think it’s the opposite of what’s happening in the political climate of divisions, of folks not talking to each other. There’s increased communication going on between scientists and managers where we’re able to do more science-based management and scientists are doing more research that’s relevant — immediately relevant — to management.” “Swamp and Pipeline, Cancer Alley, Louisiana” by Richard Misrach, 1998, museum purchase, gift of Dr. and Mrs. David A. Cofrin

40 40 Spring Spring 2019 2019

CHRISTINE ANGELINI

“MY DREAM IS FOR FOOD SECURITY WORRIES TO BE SOMETHING OF THE PAST.” Pedro Sanchez, Professor of Soil and Water Sciences, Institute of Food and Agricultural Sciences A World Food Prize Laureate, Sanchez led a team that tripled rice yields in Peru in the 1970s and has been instrumental in boosting corn yields in sub-Saharan Africa, which have nearly doubled since 2005. Farmers in more than 20 countries use the soil-improvement strategies he helped develop. “My hope is that in 20 years, we can say, ‘Remember when we were worried about food security in the world? Remember when nutrition was a concern? Remember when agriculture was damaging the environment?’ My dream would be that in most countries, this will be something of the past.” “Oscar” from the series Terrain, by Jackie Nickerson, 2012, courtesy of the artist and Jack Shainman Gallery, New York

“THE AMAZON IS ESSENTIAL.”

PEDRO SANCHEZ

Robert Walker, Professor of Geography and Latin American Studies, College of Liberal Arts and Sciences and Center for Latin American Studies Walker combines remote-sensing data and field interviews of farmers, loggers, ranchers and indigenous groups in the Amazon to reveal threats to the area and its people. “A disturbance on one part of the global surface can impact a place far, far away. Some computer models show that a desiccated Amazon could actually reduce rainfalls and affect agriculture in the Mississippi Valley,” he says. “The Amazon is the richest store of biodiversity on the planet. You need to have that in order to keep the planet capable of evolutionary adaptation … and anyone concerned about cultural variety and the integrity of native peoples has to place very high value on the Amazon.” “Yanomami” by Claudia Andujar from O Invisivel series, 1976, courtesy of Galeria Vermelho, São Paulo

ROBERT WALKER

John Jernigan

MAPPING THE 100 TRILLION CELLS THAT MAKE UP YOUR BODY BY DR. MARK ATKINSON

here are about 100 trillion cells that make up the human body. A new megascience endeavor will catalog and image each of the 200 or more types of cells from the 80 known organs and identify the genes that are active in these cells. This new effort follows on the heels of the Human Genome Project that engulfed biology during the 1990s and early 2000s. Now scientists have conceived a new and exciting challenge: to create a cellular map of the entire human body, a project called the Human BioMolecular Atlas Program, or HuBMAP. The University of Florida is one of five participating tissue mapping centers. Here at the UF Center we are charged with mapping the thymus, lymph node and spleen — all key components of the immune system. I have been studying Type 1 diabetes, or juvenile diabetes, for nearly 35 years and along with my other colleagues at the UF Diabetes Institute have been trying to find a way to prevent and cure the disease. This has been a challenge until recently, because we didn’t know what caused Type 1 diabetes. Our goal as a tissue mapping center is to identify the unique types of cells, which proteins they produce and which genes are turned on, and build a virtual threedimensional model of each organ. This map will inform the research of many diseases, including Type 1 diabetes. Why is understanding the causes of Type 1 diabetes important? We know that Type 1 diabetes is a so-called “autoimmune disorder.” In Type 1 diabetes, immune cells known as “T lymphocytes” are thought to destroy the pancreatic beta cells that are responsible for producing insulin, which regulates the level of sugar in our blood. Just over a decade ago, frustrated by the inability to prevent and cure the disease, I started an initiative to collect human pancreases from organ donors with Type 1 diabetes as well as those without the disease. The latter group was collected to provide an understanding of a “normal” healthy pancreas. To date, we have collected the pancreas from more than 500 individuals. We have distributed these tissues to some

42 Spring 2019

230 projects in 21 countries around the world. The results of this effort have led to new discoveries that have rewritten our understanding about how this disease develops. Patients diagnosed with Type 1 diabetes, some 25,000 per year in the U.S. alone, face a lifelong dependence on daily insulin injections in order to survive and have a high risk of developing long-term medical complications including blindness, kidney disease, numb feet, limb amputations and cardiovascular disease. Today, it is estimated that nearly 1.25 million people in the U.S. live with this disorder. As upsetting as these complications are for individuals with the disease, perhaps even more daunting are the many daily lifestyle factors that must be controlled or accounted for to keep the disease in check: monitoring carbohydrates, estimating exercise, evaluating blood sugar levels, and administering insulin to avoid both high and low blood glucose levels. These represent just a few of the daily disease-associated challenges. For these reasons, the goal of our collective research efforts at the UF Diabetes Institute has always been to understand what causes this disease. Knowing that would enable us to predict who is at risk, identify ways to prevent the progression of the disease and develop a curative therapy. Why study these organs? Type 1 diabetes is but one of more than 80 known autoimmune diseases in which, for reasons unknown, the immune system turns against itself. Beyond autoimmunity, immune responses are also a key constituent to health in terms of fighting cancer and infectious disease. From our experience studying the pancreas and Type 1 diabetes, we see great strides in understanding the role for immunity in each of these settings

through mapping. It will allow for a deep dive of how the immune system works. In a healthy individual, T cells only become active when responding to infection or cancer cells. But in those predisposed to autoimmune disease, certain T cells can become erroneously activated by “self” proteins, leading them to destroy healthy tissue. In other circumstances — like cancer or infectious disease — the immune system fails to provide a robust enough response to be effective. Or cells of the immune system proliferate uncontrollably, leading to blood and lymphatic cancers like lymphomas and leukemias. This is why the thymus, spleen and lymph node are tissues of interest for those studying the healthy human immune system. Researchers need to understand the healthy baseline for all these organs so that we can recognize when things begin to malfunction and change, leading to autoimmune disease, cancer and infectious disease. Expressed another way, we first need to understand what constitutes the normal lymphatic system throughout the human lifespan. Why is defining normal important? You might wonder where exactly we get these normal cells. As we have done over the past 11 years, we will obtain transplant-grade human tissues from deceased organ donors through Organ Procurement Organizations, after a family member or legal executor provides informed consent. Given at a time of grieving, these precious anatomical gifts, which in the case of spleen, thymus and lymph node, are not usable for lifesaving transplantation procedures, provide an inimitable resource for scientific investigation and discovery. Only tissues considered “normal” — unaffected by known or observable pathologies — will be included in these initial studies. We will be collecting

Type 1 diabetes occurs when the immune system erroneously destroys the insulinproducing beta cells in the pancreas, which leads to high glucose levels in the blood, called hyperglycemia.

tissues from donors ranging from infants to adults up to 70 years old. We hope this will provide insights into how age alters the types and health of all the cells in each organ. At the UF Diabetes Institute a multidisciplinary team including cellular and molecular biologists, hematopathologists who study clinical lymphatic samples, biomedical engineers, immunologists and many others will collaborate for the HuBMAP program. Indeed, the UF tissue mapping center will collaborate extensively with a global network of experts in cutting-edge microscopy and data collection. We are establishing an imaging pipeline to detect dozens of protein and RNA molecules that characterize nerve, blood vessel, the supportive tissue known as stroma, and immune cells from slices of tissue, using eight different forms of microscopy. Within HuBMAP’s first two years, we plan to map the spleen, thymus and lymph node from 11 organ donors.

We expect that the resulting data will reveal new cell types, molecular and cellular structures, cell-cell interactions and their functional implications in human anatomy and physiology. Hence, the high-resolution, three-dimensional Human BioMolecular Atlas Program is expected to facilitate discovery. As I hit my late 50s in life, the number of colleagues, friends and family members that are impacted by disease increases annually. I also recently became a grandfather. I would like to think what we propose to do will have a dramatic impact on human health for both current and future generations. That would be a legacy gift. Mark Atkinson Director of the UF Diabetes Institute atkinson@pathology.ufl.edu

To read more articles by UF faculty, visit https://theconversation.com/institutions/ university-of-florida-1392

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Hive Help

UF’s Smathers Libraries have added hundreds of pages of correspondence between author Marjorie Kinnan Rawlings and her literary executor Julia Scribner Bigham to its renowned collection of materials related to Rawlings, who captured life in rural Florida through novels like The Yearling, which won the Pulitzer Prize in 1939. Bigham, whose father Charles was Rawlings’ publisher, was a close friend of Rawlings from the late 1930s until the author’s death in 1953. She served as literary executor of Rawlings’s estate until her own death in 1961. There are nearly 300 items in this carefully preserved archive, which is rich in personal detail. Subjects of their discussions include the creative process, music, religious faith, politics, mental health, marriage, motherhood, and professional employment. They also discussed many writers one or both of them knew personally, such as Margaret Mitchell and Robert Frost. The collection also provides a remarkable window into American literary politics and publishing after World War II, casting light on fundamental questions about things like the relationship of author and editor and the experiences of female authors. This collection was donated by Nicholas Meriwether, son of the late James Meriwether, a literary scholar who had purchased the collection from a dealer in 1988.