Our DNA - Spring 2018 by University of Utah - College of Science

N E W S for A L U M N I

BIOLOGY NEWS | SPRING 2019

Contents Publisher School of Biological Sciences

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From the Director

A Successful First Year

Reshma Shetty

A glimpse of the startup life

Direct correspondence to: University of Utah School of Biological Sciences 257 S. 1400 E., 201B Salt Lake City, UT 84112-0840 pace@biology.utah.edu

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Faculty Spotlight

Gone Fishin’: cell biologist and former undergrad advisor Dave Gard now angling on the Green

Alumni Spotlight

Rajesh BS’86, Monica BS’91 and Leena BS’92 Gandhi

Jeanne Novak BS’81 PhD’87

Research

Geneticist Nitin Phadnis uncovering genomic conflicts to solve the “mystery of mysteries”

School Director M. Denise Dearing

Editor David G. Pace

Contributors Matt Crawley Paul Gabrielsen Nicole Morgenthau Lisa Potter

Outreach

Diane Pataki’s Landscape Lab creates a living experiment in which everyone becomes an investigator

Stay connected Visit, respond, subscribe, donate: www.Biology.utah.edu

On the Cover “Darwin’s Fancy.” The Jacobin shows the spectacular genetic variation of the domestic pigeon. The Shapiro Lab studies the genetics of animal diversity using a number of these beautiful birds. Photo: Michael D. Shapiro

Request an e-version of OUR DNA in place of a mailed copy at development@biology.utah.edu

FROM THE DIRECTOR

A lighter moment in an undergraduate teaching lab in the Crocker Science Center. Photo: Matt Crawley

A Successful First Year D

ear Alumni & Friends,

Our first academic year as the School of Biological Sciences was a smashing success! We launched a new year-long Introductory Biology course that gives our undergraduates experience doing biology, from hands-on labs to in-class analysis of biological data. Here’s what students are saying:

“We don’t know what our soil sample will yield in the lab, and neither do the instructors. We can arrive at different conclusions in different ways or the same conclusion from different paths—real science.” “You don’t really enter the lab knowing what you’re going to walk into—in a good a way.” “You get a deep dive in the subject rather than just a broad view of something. It’s very hands-on.” And the faculty have commented on the increased student engagement. Our research capacity in the School continued to grow this year. The $6 million Titan Krios cryo-electron microscope housed in the new Crocker Science Center produced its first images this winter. And we have expanded our capacity to

give our undergraduates cutting-edge research experiences with the establishment of the Biology Research Scholars Program. This program is made possible by a lead gift from Jenny & Ryan Watts with supporting gifts from Ole Jensen, Mark Skolnick and George Riser. Stop by next fall for our first symposium to see what our Scholars have been working on. This May we will launch the 2019 cohort of Biology graduates that includes 185 students with undergraduate degrees and twenty students with graduate degrees. We wish you all the very best in your future endeavors and encourage you to stay connected to your roots in the School of Biological Sciences!! And past graduates… we would love to hear what you are up to now. This newsletter is a venue for sharing your information and keeping connected. Please send us your updates: development@biology.utah.edu All the best and enjoy your summer, Sincerely,

M. Denise Dearing Distinguished Professor, Director School of Biological Sciences 1

Reshma Shetty A glimpse of the startup life

By continuing her biology research while pursuing a degree in computer science, Shetty built an interdisciplinary research foundation that she carried to graduate school at the Massachusetts Institute of Technology, and beyond to Gingko Bioworks. On February 21, 2019, Shetty returned to the U to share her experiences and words of wisdom with participants in the ACCESS program for undergraduate women in STEM fields as well as others from the U’s College of Science. She told the story of establishing Gingko Bioworks along with a few other graduate students at MIT. “We were not used to having any money, and that really helped,” she said. The group managed to purchase laboratory equipment, at a substantial discount, from other biotech companies struggling during the Great Recession. “We used the scientific method to build ideas and our business model,” she said.

Reshma Shetty was invited to meet with undergraduates of the School in March. Photo: David Robert Thomas

Now a company of around 200 employees, Gingko is taking on challenges such as engineering nitrogen-fixing microbes to increase agricultural yields. As a company leader, Shetty is shaping the company’s culture and commitment to a diverse workforce. “The culture reflects who you are and who you want to be,” she said. “Diversity is a competitive advantage.” Students came away inspired by Shetty’s story.

t all started with venomous snails. University of Utah alumna Reshma Shetty BS’02 is now an executive of the growing Boston biotech firm Gingko Bioworks, which she cofounded in 2008. Gingko Bioworks engineers biological organisms for a variety of commercial and industrial uses, including engineering organisms to manufacture specified chemical compounds. The company has been called “the future of” industries from fragrances to pharmaceuticals. But her road to becoming a biotech pioneer began as a high school student in the laboratory of U biology professor Baldomero “Toto” Olivera.

That’s where she met the snails. Throughout her undergraduate years at the U, Shetty studied the venomous compounds produced by the snails to explore their function and possible pharmaceutical applications. “The tradition of undergraduate research is something that is really special and unique about the U,” Shetty said. “I haven’t seen that tradition in a lot of other universities to the same extent.” 2

“She mentioned that creating a business mission is similar to conducting the scientific process,” said Caitlin Gallivan, an Honors student in Chemistry. During the presentation, Gallivan said she “felt a sense of community among a group of individuals who all share a passion for science and innovation.” “Designing organisms is something that sounds almost like science fiction,” said Audrey Brown, an Honors student in Biology, “but the fact that it is a reality is super cool and shows the potential impact that science could have.” “Being able to meet an incredible alumna that was once in our position as undergraduates was inspiring and encouraging,” said Sahar Kanishka, who is double majoring in Biology and Business. “As a student in STEM, the options seem limitless in what there is to pursue.” Shetty’s visit and presentation were supported by the College of Science, the School of Biological Sciences, BioLuminaries, inSTEM and ASUU.

Briefly Noted Ole Jensen BS’72 recently edited the 3rd edition of The Sinus Bone Graft. Mark Durham, DMD at the U’s School of Dentistry says of it, “This is the source book on the topic. The international network of clinical scientists, required to assemble the essential knowledge on this critical but highly esoteric topic, cannot be overstated. Dr. Ole Jensen, with his international renown as one of the world’s leading experts in oral reconstruction, is considered one of the few people who could assemble such a diverse, broad, and profound team of authors on such an important topic. The profession is fortunate to have a volume of work on this scale, and an international leader who made it happen.” Craig Thulin BA’89 worked in the labs of Dr. Baldomero “Toto” Olivera among others before moving to Seattle to secure his PhD in Biochemistry. At what is now Utah Valley University he joined the Dept. of Chemistry and from 2004 to 2008 was an adjunct in Obstetrics and Gynecology at the U School of Medicine. This stemmed from Thulin’s research looking for serum proteomic biomarkers of complications of pregnancy and led to the formation of a startup company called Sera Prognostics. Today he continues to lead students in mentored undergraduate research, collaborating with faculty members at BYU and Utah State University, and working on investigations on the bioanalytical chemistry of honey. Russell Marion Nelson Sr. BS’45, former surgeon and long-time leader in The Church of Jesus Christ of Latter-day Saints became its president in January 2018 at age 93. He was a member of the LDS Church’s Quorum of the Twelve Apostles for nearly 34 years. A native of Salt Lake, he earned a PhD at the University of Minnesota, where he worked on the research team developing the heart-lung machine that in 1951 supported the first ever human open-heart surgery using mechanical takeover of heart and lungs (cardiopulmonary bypass). A medic for the U.S. Army during the Korean War, he returned to Salt Lake as professor at the U’s School of Medicine in 1955. Heng Xie PhD’04 taught middle-school science before joining the team as senior scientist at IDbyDNA, a start-up that has developed transformative metagenomics technology to simultaneously profile tens of thousands of microorganisms and pathogens in any sample. At the U Xie worked with Kent Golic in his lab studying genetics and cell biology. Xie hasn’t left public education entirely. When she isn’t working in R&D in Salt Lake City where the lab and offices of IDbyDNA are located, she tutors students in biology, chemistry and math, including calculus.

Taryn Wicijowski BS’14 took her Pac-12 Scholar-Athlete of the Year talents overseas, in 2015 joining the top basketball league in Italy. “I found professional basketball to be much more about individual statistics and achievements than collegiate [ball],” she says. Eventually, she was accepted to the medical school at the University of Alberta, close to Saskatchewan where she’s originally from. “I have had great patient interactions,” she reports. “Each experience makes you feel like you’re really making a difference in peoples’ lives and further motivates you to one day be a physician.” Michael T. Ghiselin BS’60 is a biologist, and philosopher as well as historian of biology. Currently scientist-in-residence emeritus at the California Academy of Sciences, he is known for his early work on sea slugs, and has had both a species (Hypsedlodoris ghisenlini) and the defensive chemical that it contains (ghiselinin) named after him. Widely quoted on the relationship between science and society, he is perhaps most known for the dictum, “Scratch an altruist and watch a hypocrite bleed,” first recorded in 1974 in his book The Economy of Nature and the Evolution of Sex. Photo by Alan E. Leviton, with permission James F. Berry PhD ’78 joined the faculty at Elmhurst College in Illinois, and taught biology courses there until he retired in 2017. He received a JD degree from IIT Chicago-Kent College of Law and spent his law career teaching both biology and environmental law. The author of many articles (and two books) about the biology of freshwater turtles and environmental law, including The Environmental Law & Compliance Handbook, he is now retired near Charleston, SC, where he continues to teach an online biology course. Daina Graybosch, BS’01 completed a PhD in Chemistry and Chemical Biology from Harvard. Today she is Senior Research Analyst covering Immuno-Oncology at SVB Leerink, a leading investment bank in New York City, specializing in healthcare. Prior to joining the firm in 2018, she worked at McKinsey & Company as a Senior Expert and Head of McKinsey’s Center for Asset Optimization, as well as the U.S. Head of the McKinsey Cancer Center. In these roles, she developed several McKinsey solutions that bring data and advanced analytics to pharmaceutical development decisions. In her 11 years at McKinsey, she developed a rich understanding of oncology through her work with companies across the value chain, including Pharmaceutical, Diagnostic, Academic Medical Center, and Genomic/Data. Briefly Noted, continued page 5

FACULT Y SPOTLIGHT

Gone Fishin’ Cell biologist and former undergrad advisor Dave Gard now angling on the Green

s a graduate student during the 1980s, Dave Gard recalls the first time he saw muscle cells he was growing in a petri dish begin to twitch. He was hooked. Cell Biology became his passion, whether in his lab investigating the assembly and organization of microtubules in frog eggs, or in the classroom teaching cell biology. After completing his PhD at Caltech and post-doctoral fellowship at UC San Francisco, Gard joined the Department of Biology in the summer of 1987. For the next twenty-three years, he and his students studied microtubules, microscopic filaments required for a myriad of cellular functions in eukaryotic (nucleated) cells. In 1989, Gard secured funding for the first laser-scanning confocal microscope in the Intermountain West. Using this technology, he and his students spent thousands of hours studying the organization and role of microtubules in frog oocytes, eggs, and embryos. When the confocal he had labored over for a decade became obsolete, it was replaced with a next generation scope. “We sold [the first confocal] for parts,” he opines, “but not before I entertained the thought of hiding away a note inside the machine’s scan head with ‘Dave Gard was here!,’” a nod to the ubiquitous “Kilroy was here!” seen in graffiti during WWII. Around 2000, Gard’s research interests took another turn. Molecular studies by his lab and others around the world had revealed proteins related to XMAP215 in both evolution and function, known as “homologs.” They were to be found in many if not all eukaryotic cells–those distinguished by the presence of a nucleus and organelles enclosed by a plasma membrane.  Dave Gard on the Green River with a German Brown. Photo: Darryl Kropf

“It was neat, and sort of mind-boggling,” he says “to realize that a protein you discovered might be a critical component required for the evolution and life of eukaryotic cells.” Eventually, Gard found a new passion as the School’s Director of Undergraduate Advising. From 2010-2015 he helped shepherd thousands of undergraduate majors though the maze of classes required to earn their biology degrees. “It was crazy at times,” he recalls. “I averaged nearly two thousand, twenty-minute appointments a year.” Well-known for his infectious enthusiasm, Gard received many awards, including the U’s Distinguished Teaching Award in 2015. He taught several lecture and lab courses during his career but is perhaps best known for teaching BIOL 2020: Principles of Cell Biology and the honors section 2021: Principles of Cell Science. He estimates he taught these courses at least thirty times to nearly 6,000 students, many of whom

went on to medical or graduate school, or to other successful careers in the sciences. Now emeritus, Gard hopes to spend much of his retirement with his wife Anne and her horse(s), his son Liam (a first year student at the U), and his daughter Tina who graduates from high school this spring. Gard also hopes to pursue some of his lifelong hobbies, including his passions for steam trains (full-sized and models), and collecting and playing Guild acoustic guitars. These days, however, you’re most likely to find Gard roaming the banks of a local river, fly rod in hand. Or, look for him floating the Green with his fly fishing buddies from Biology, Darryl Kropf (also emeritus), and Gary Rose, in a drift boat they jointly purchased in 1995. Gard quips, “After thirty-one of these annual trips, we still ‘fish till it hurts,’ but it hurts a hell of a lot sooner than it used to!”

 Briefly Noted, continued from page 3

Austin Green, PhD candidate, was awarded an Alta Sustainability Leadership Award for his citizen science project Wasatch Wildlife Watch. With two sites, one in Salt Lake and one in Logan, hunters, public lands advocates, public school teachers and university students work with 305 trail cameras to photograph wildlife through motion-sensors. This data will help developers and city planners institute sustainable practices as the Wasatch Front grows. A detailed story about the project appeared on the front page of the Salt Lake Tribune earlier this year. Taylor Thompson BS’14 is a bantamweight mixed martial arts (MMA) athlete based in Boston. She first discovered MMA through a course she enrolled in while an undergraduate student at the U. “I had no idea what it was,” she says. “I thought it was going to be … kind-of dabbling in all of the very traditional martial arts. I thought that would be a fun way to get some athletic credit done.” After graduation she attended veterinary school in central Massachusetts where she continued the sport, eventually going full-time. A fullcontact combat sport that allows striking and grappling, both standing and on the ground, using techniques from various combat sports and martial arts, MMA first signed women on to the sport in 2012. You can follow her career on Facebook @ TaylorThompsonMMA. Photo: Igdalia LLC Michael Shapiro, faculty member known more for his work with pigeons (see cover of Our DNA) than cinema, reviewed science-related films at the 34th annual Sundance Film Festival. He along with a team of others donned Science@Sundance hats and reviewed ten films, including The Great

Hack, I Am Mother, and Ask Dr. Ruth, a documentary of the diminutive celebrity sex therapist. The Festival’s theme “Risk Independence” emphasized Sundance’s provocative themes and experimental storytelling. In Science Magazine where the reviews appeared in March, Sundance Institute’s Keri Putnam said, “Art can’t spark conversation if it’s playing it safe.” The same could be said of science. Sarah Bush, faculty member, also works with pigeons… but focuses on their relationship to lice. She, Michael Shapiro and others reported in Evolution Letters on experimentally triggered adaptive radiation. By placing feather-eating lice on white, black, and gray pigeons, they showed how the parasites change color to better blend in. The researchers showed that descendants of a single population of feather lice adapted rapidly in response to preening, the pigeons’ main defense. “People have been trying to bridge micro- and macro-evolution for a long time,” said U biology faculty member Dale Clayton and another co-author of the paper. “This study actually does it.” The research was also featured prominently in The Atlantic. Dale Forrister, PhD candidate, was the lead author of an article recently published on diversity in tropical rain forests. The paper appeared in Science, and was co-authored by Phyllis Coley and others. While 650 different tree species can exist in an area the size of two football fields, similar species never grow next to each other. Add herbivore pests and you have warfare for survival. For the first time these biologists compared the two combatting factions in a single study. The study reveals the significant role of herbivores in driving diversity in tropical ecosystems, with stark implications—the loss of those populations could have catastrophic consequence on these important habitats. 5

ALUMNI SPOTLIGHT

The Gandhi siblings: Monica BS’91, Rajesh BS’86, and Leena BS’92

The Gandhi Effect An alumna’s return to her roots as convocation speaker merits a visit with her and her two alumni siblings who are also medical doctors 6

ast December, when the three Gandhi children, Rajesh BS’86, Monica BS’91 and Leena BS’92 returned home to Salt Lake City—two from one coast, and one from the other—they celebrated their parents fifty-fifth wedding anniversary. As alumni, all three, from the School of Biological Sciences, they must have had a lot to reflect on.

Their father, Om, now aged 84, had brought his young family to the U in 1967 during the “summer of love” from their native India when Rajesh “Tim,” the only child at the time, was three years old. A Professor of Electrical Engineering at the U for over 50 years (and former department chair) Om has since retired. Says Rajesh, “We essentially grew up in the Merrill Engineering Building.” He and his sisters remember department picnics and other college events. “We were especially impressed as children with all of the colored chalk they had in the classrooms,” remembers Rajesh. Both Om and the Gandhi children’s mother (Santosh) had to leave home at a young age to pursue further education. After Om earned his PhD at the University of Michigan in the late 50s, he returned to the subcontinent where he taught physics for a time in a small town in India before accepting an opportunity to return to the U.S. He chose the U. Once the children were older, Mrs. Gandhi returned to school herself, and even took classes from her husband. Far from showing her favoritism, he insisted on only answering her questions during office hours! She eventually finished her degree in computer programming before taking a position at the Salt Lake branch of 3M. It was an educated family, for sure, and all in the sciences. It was also a family inextricably tied to the University of Utah. All

three of the Gandhi children attended the U because it was local, “a function of my parents’ having to leave home early [in their studies] in post-partition India,” says Monica who attended Harvard for her MD and who is currently Professor of Medicine and Associate Chief of the Division of HIV, Infectious Disease, and Global Medicine at UCSF. She also serves as Medical Director of the Ward 86 HIV Clinic at San Francisco General Hospital, one of the oldest HIV clinics in the country. All three siblings remember the excitement of coming to the U after going to public schools in the 1970s/80s, recalling how it broadened their horizons from the more limited experiences they had growing up. “We were all pretty much wedded to the U. Part of our ethos growing up” in Utah, continues Monica. Attending the U was liberating, they say, mind-opening with a bit of counter-culture at play after going through the public school system in Salt Lake. And certainly it was formative. “I was moved to enter HIV care,” says Monica, “after growing up in a place where I saw friends coming out as gay in high school struggle with stigma. I also became interested in infectious diseases, which differentially affect the poor, after going to India several times as a child to visit grandparents and witnessing the stark contrast between rich and poor. This set me on the path to medical school.” Beginning her sophomore year Monica worked on chemotaxis in E.coli with her undergraduate advisor Dr. John (“Sandy”) Parkinson in his lab. She will be returning to Utah as this year’s convocation speaker in May. She describes the Bay Area where she currently lives as a place “that couldn’t be more different than Utah.” Although San Francisco is generally a place where gay and transgender individuals have sought refuge from more conservative places throughout the U.S., “stigma towards people living with HIV still exists and must constantly be combatted,” she says. Before Monica enrolled in the U, Rajesh, five years older, worked in Dr. Baldomero “Toto” Olivera’s lab, the celebrated faculty researcher whose subject model is poisonous cone snails. “Toto was an incredible mentor to me and to countless others,” says Rajesh. “He taught me the transformative power of science and set me on the road to a career in biology and medicine. I would not be where I am without his encouragement and influence.” Rajesh’s U experience was as much about philosophy and history as biology. Both he and Leena remember fondly the five-term Intellectual Traditions of the West colloquia with professors like the beloved theologian and classicist Dr. Sterling McMurrin. “At the U, I experienced a whole new world from my time in public schools,” says Rajesh. “It was a place packed with people of diverse experiences, interests and perspectives. It was a vibrant and exciting place to be.” Around the time Rajesh entered medical school, also at Harvard, he recalls with Monica, the state of affairs of that singular time in American medical history. “HIV was just ramping up. It was a devastating disease and one that was being defined in front of our eyes.” Between 1988–90, the

medical sector was furiously attempting to figure out how the disease manifested itself. Treatments were very poor. He especially admires Kristen Ries, MD, MCAP who for a time was head of the clinic at the U serving HIV/AIDS patients. The difference, he says, between the attitude toward the sick in small towns compared to, again, a place like San Francisco at this time was “very moving to me,” he says. Currently, he practices medicine in Boston where he is a specialist in infectious disease and Medical Director of the HIV Clinic at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School. He is also actively involved in HIV clinical research, working on discovering a cure for HIV—the disease that defined his generation.

Attending the U was liberating, they say, mind-opening with a bit of counter-culture at play after going through the public school system in Salt Lake. And certainly it was formative.

While all three Gandhis ended up as medical doctors, Leena, who has focused on oncology for the past 10-plus years, currently leads early drug development at Lilly Pharma. Leena earned her PhD at the University of California Berkeley in DNA replication studies before attending New York University for medical school, followed by her residency at Mass General and a fellowship at Harvard Medical School, both in Boston. She characterizes her experience at the U as providing “a genuine ‘college experience’. [The School of Biological Sciences] …was all about scientific inquiry,” she says. “I learned something every day from [then] junior faculty like Dr. Mary Bekerhle [now head of the Huntsman Cancer Institute].” Leena also worked in Ted and Tucker Gurney’s lab in cell biology. “The spirit of scientific inquiry was everywhere,” she continues, “and it really motivated me to go on for a PhD in the science of medicine and the early development of drugs… At the U, I learned that science drives how we interact at the macro level. It was very grounding.” With the benefits of the novel field of immune-oncology, Leena still has patients who have been free of cancer for more than ten years. But, of course, there is still work to be done. “At Lilly I’m able to do work at a much larger scale and with a much broader population.” The Gandhi Effect found in Rajesh, Monica and Leena Gandhi— from “sea to shining sea”—is indeed a rarity, what one might call “A Triple Threat” that the School is proud to embrace. 7

ALUMNI SPOTLIGHT

Jeanne Novak | CBR In 2014 alumna Jeanne Novak found herself at Ebola ground zero. She was ready.

That summer underscored the importance of the work CBR has done for more than two decades in helping research companies and regulators navigate layers of rules that make it complicated to ship unproven drugs overseas, let alone try them in patients. “We played a pivotal role in designing the filing [of ZMapp],” says Novak. “CBR was proud and humbled to help.” Ultimately, only seven individuals could be treated with the new drug. Five of those seven survived. Thankfully, the crisis abated soon after. The pressure on CBR and Mapp was off, but the imperative to competently, inexpensively and expeditiously move new drugs like Fibrocell Science’s lead product laViv, approved earlier in 2011, through the regulatory pipeline remained.

A Scientist First

Jeanne Novak, PhD. Photo: Joan Lawson

he Ebola outbreak in the summer of 2014 was a long way from CBR International (CBR) in Boulder, Colorado. But for several weeks the Company, which helps clients research new drugs and navigate U.S. Food and Drug Administration review of them, reconfigured into a kind of war room.

Jeanne Novak BS’81, PhD’87, founder and CEO of CBR, had just returned from the World Health Organization meeting on the emergency. She and her team had been working with Mapp Biopharmaceutical Inc., the San Diego-based maker of ZMapp, a treatment for Ebola that had still not completed its trials in animals, let alone humans. 8

Wisconsin-born, Novak was admitted to West Point Academy after high school graduation. She moved to Utah shortly thereafter where she completed her bachelor’s in biology at the U, followed by a PhD in Experimental Pathology (Cell Biology and Immunology). Also, in 1979 she became the first female ROTC Battalion Commander (Army) in the state of Utah. She founded CBR (originally Colorado BioReg) in 1999. That Novak—author, lecturer and development advisor to industry as well as governments worldwide—is a scientist first both determines the direction and creates the culture of CBR. She credits U Biology for her enduring ethic, deeply-rooted in basic science and the empirical method, for her success as an internationally-recognized authority in the biotechnology and pharmaceutical industries. “You don’t realize until you’re really out there, and you look back and you’re in the environment with other scientists just how great an education I received [at the U],” she says. As a grad student “many times the reason I even knew about other departments was that we had joined them in seminars and classes that we got to take as

undergraduates… with faculty like Don Summers, [Nobel laureate] Mario Capecchi and [Department Chair] Gordon Lark.” In what is now the School of Biological Sciences Novak learned how to reflexively interrogate her assumptions, even her own empirically-driven findings. Typically as an undergrad “there are courses you take, there’s regurgitation, you move through it, you’re motivated by grades. But that wasn’t the sense I got there… . Consistently, the theme was to learn how to think.” She identifies the way the School’s curriculum was developed and organized, the lab courses offered, the fact that there was “no skimping… It was second to none.”

The CBR Touch Novak’s success is based not only on her training and commitment to basic science but also to the “service side” of her. This internal, two-piston engine has manufactured a suite of companies, including one based in Berlin, specializing in moving foreign companies through both U.S.’s FDA and the European Medicines Agency. The Company is more than a consulting firm in that it provides services to help the client move through the process of approval and the regulation of new products. The partnership isn’t just a clerical one, filling out forms and advising on next steps. Instead CBR helps clients design the analytical methods in the lab, helps strategize and then deploy processes, including animal trials, essential to winning approval and meeting regulatory standards. From there, the Company assists with manufacturing and all stages of clinical development. CBR’s approach to product regulation is less about a transactional model and more of a conversational one. It’s an approach designed to make the company, in a sense, ultimately obsolete to its clients. Through full-blooded partnering, the client-company creates its own opportunities, its own protocols and, using the CBR-owned TruSubmit software (licensed from Extedo), is able to coordinate in-house their own application to the FDA or the equivalent in Europe. This is what happened with the company that produced ZMapp, the drug engineered to fight Ebola. After the 2014 crisis, Mapp developed its own regulation department to expedite new drugs and devices. We help “our clients to learn as they go,” Novak says. In turn we hope “they will take it forward to their next project, [and assemble an] experienced, educated staff. Whatever programs they have can then be [managed] in an informed way.” The partnership approach helps create an inner-directed, learning process in the client–what Novak calls “The CBR Touch.”

The “Service Side” Partnering with organizations in this way is part of the enduring “service side” of Jeanne Novak, a side that stems from her days as a commissioned officer in the U.S. Army and U.S. Public Health Service. Early on, as a science fair judge in Maryland, she noticed that students weren’t finding encouragement to

produce projects motivated not just by science, but by science applications. Novak founded an award given to applied science projects, sponsored by the Commissioned Officers Association in Washington DC. It was a pilot soon brought to scale at science fairs nationwide and continues today. Novak understands the need, in part crystallized by her experience working at the FDA to deliver drugs and medical devices to the public quicker and at a more affordable price. “We have a number of biosimilars [new products close enough in duplication to accomplish the same therapeutic and clinical result as the drug it is “similar” to] and personalized medicines using cutting-edge treatment modalities,” she says. But these bio-tech products are expensive to develop, license and commercialize. Some cancer therapies can cost as much as $100,000 per year, per patient. “We’ve come into a legal and regulatory place,” she continues, “in which we make products from an expeditious path: six instead of ten-to-fifteen years.”

“I believe in great education. But how do we continue to help young minds not just take the first answer they come upon?”

Meanwhile, CBR which at its largest has internationally employed a surprisingly small number of scientists and regulatory specialists, forty, remains through its research and work model solvent and growing. Yet rarely, if ever, has the Company put out requests for proposals, instead using referrals to secure new clients. Recalling her own “stellar” education at the U, Novak, who is looking forward to retirement and continuing her adjunct appointment in cell and molecular biology at Colorado State University says, “I want to help young people take information forward and to make products.” Pursuant to that, she is still asking her own research question: How do we continue to inspire young scientists when information is a little too easy to get? “I believe in great education,” she continues, “from the traditional library to Google. [But] how do we continue to help young minds not… just take the first answer they come upon? Even young scientists are prone to do that today.” Instead, students need to learn to rigorously investigate their empirically-derived data sets, to look further beyond first-draft conclusions. “You ask me what the next step is for me: it’s to bring in young undergraduates, to help them learn how to think.” 9

RESEARCH

Geneticist

Nitin Phadnis Uncovering genomic conflicts to solve the ‘mystery of mysteries’ High-density housing in Nitin Phadnis’s lab: fruit flies live and breed in thousands of vials. Photo: Michael Schoenfeld

he first thing one notices on a tour of the Nitin Phadnis lab in the South Biology Building is the distinctive scent of cornmeal and molasses: room and board in thousands of plastic, numbered vials for the millions of fruit flies (Drosophila pseudoobscura) which are the subject of his research. Back in his office it’s more of a visual that you notice: a floor-toceiling white board with curious hieroglyphics at the bottom that look distinctively like that of child’s. These are not the markings of flies but of other small individuals. Phadnis is a father of a daughter and the white board has clearly been a tempting tabula rasa while visiting dad away from home … temptation with limited reach, at any rate.

Above these intriguing chicken scratches from tiny hands, there are formulas and graphs detailing the work of this geneticist who is asking, “how do new species evolve, anyway?” It’s a question that has driven his research since his arrival at the School of Biological Sciences in 2014 and is underscored by the energizing fact that the principles of biology, unlike mathematics and physics, are relatively young. “It’s been relatively recent that we even learned the structure of DNA,” Phadnis reminds you. “We didn’t have CRISPR gene-editing technologies or some of the advanced sequencing technologies even five years ago. There are a lot of unknowns still.” 10

Unknowns are what inspire this thirty-eight-year-old native of India who initially wanted to be an astrophysicist but found the questions in evolutionary genetics more interesting, and personally motivating. His lab attempts to answer questions about how new species arise and how silent but powerful evolutionary conflicts inside genomes drive cryptic changes. Speciation, the process by which one species splits into two, involves the evolution of reproductive isolating barriers such as the sterility or inviability (when an individual is unable to survive or develop normally) of hybrids between previously interbreeding populations. Cracking the code of how new species split from existing species hinges on understanding how and why such hybrids break down. Phadnis is quick to recall Darwin’s On The Origin of Species, in which the father of evolutionary science could find no satisfactory solution to the apparent paradox of why natural selection would tolerate the onset of these genetic barriers. Think of the mule: a cross between a horse and a donkey, but never able to sexually reproduce. The question of why mules and other hybrids are unfit has been pondered over since the days of Aristotle. Darwin called this problem the “mystery of mysteries.” Uncovering the molecular and evolutionary basis of speciation involves, first, the identification of genes that cause hybrid sterility

and inviability. Second, it involves uncovering the molecular mechanisms of hybrid dysfunction from these genes. Even in today’s “post-genomics” era, identifying such genes and their molecular mechanisms remains an absurdly difficult challenge. But “[d]espite decades of intense efforts,” writes Phadnis, “very few such genes have been identified. We know even less about the evolutionary forces and the molecular developmental pathways that are disrupted in hybrids.” Since Darwin there have been different angles of attack to de-claw the mother of all evolutionary mysteries. There have been new lines of inquiry, new research questions. Relatively speaking, these questions are old, but they are now being approached by new technology through collaboration with human genetics, surgery, human data sets and other disciplines and information. “This style of science,” says Phadnis, “couldn’t be addressed in other institutions as easily as it is at the U of U” where a major health sciences campus is so close (and so collaborative) to biologists, engineers and others. This proximity of resources is especially helpful attacking problems in what’s known as genomic conflict. Such conflicts within genomes can lead to the evolution of hybrid incompatibilities, which reduce the exchange of genetic variants between species. Such reproductive barriers that stop the exchange of genes between populations are key to speciation. A critical question that Phadnis is asking as he and his team look at fruit flies which, conveniently, reproduce every eleven days, creating a new generation, is why such hybrid incompatibility genes evolve so rapidly. It likely has something to do with competing, out-of-sync factions warring under the scope. “They are like arms races inside of genomes,” he says. These are dancers in which one partner suddenly speeds up the tempo, leaving the other at least temporarily lagging behind. This leads “to the rapid evolution of essential machinery” on the molecular level. For example, “when these silent but fierce wars occur inside genomes, the arms races are played out with: You build this? Then I’ll build that!” There are waves of these fierce genomic battles, and the cellular machinery involved in these fights can often evolve very rapidly. Figuring out how that machinery works involves first locating the “cheating chromosomes” and performing long-read sequencing to find the break points (what’s known as chromosomal inversion). Using CRISPR, the research scientist re-engineers those points and “flips” them back to the original positioning or sequence. Returning to the combat metaphor, what the researcher is doing is identifying where the cheating is happening by spying on or “apprenticing” with a master chromosome cheater. These master cheaters are deeply familiar with the rules, enough to know how to break those rules and gain the advantage (win) in forming hybrid organisms. The researcher, by adding what Phadnis refers to as “deep evolutionary thinking” to the process, can then learn of previously unknown but profoundly impactful molecular techniques. Mapping genes of hybrids whose reproductive proteins separately evolve so quickly helps Phadnis see why they’re

“messed up,” and the “mess ups” have implications for human infertility. How is it that in some human gene pools the future of an entire sex can be wiped out as “cheaters” eliminate the 50/50 pairings of XX and XY chromosomes designed by nature to roughly equal numbers of males and females to promote the survival and evolution of a species? Other questions quickly follow: Do these cheating chromosomes exist in humans and can we design ways to find them? What are the other cheating mechanisms these rogue chromosomes use? Will these expected forthcoming conclusions add to the literature of how infertility occurs in humans and how it can be prevented? Does it lend to predictions about the sex of outcomes/births? These questions will inform Phadnis’ next steps, exploiting rich collaborations with other University of Utah research and academic units virtually a stone’s throw from the School of Biological Sciences. Up the hill in Human Genetics, for example, there is much to learn about sperm cells that are not “fertilization-competent.” Clearly, these little swimmers are not all created equal. Can we build a kind of race track or Olympicstyle swimming pool to better observe and learn from these inter-male sperm competitions? Can those competitions (or sperm pools) be sequenced with CRISPR or some other related technology? Are we about to provide a “hook” for an entirely new line of scientific inquiry?

“When these silent but fierce wars occur inside genomes, the arms races are played out with: You build this? Then I’ll build that!”

“There are lots of amazing things going on these days in biology,” concludes Phadnis, referring to these questions and many more. The persistent odor of corn meal and molasses, the ubiquitous piping everywhere through which flows carbon dioxide to put fruit flies to sleep before observing them–it’s certainly worth all of this. Nitin Phadnis nods with a smile at the empaneled sketches by the tiny hands of his daughter. Is that a bird there? A roughly hewn model of a mitochondria over there? Perhaps flailing stick figures of mom and dad? “Here at the U you can actually come up with original ideas to solve long-standing problems by bringing teams of people together with different expertise. And biology,” he reminds us, “is the hub of all that. It unites all of life sciences. We’re the collection of misfits and trouble-makers,” he muses. 11

OUTREACH

Call of the Wild:

A Socio-Ecological Approach to Human Habitats Diane Pataki’s Landscape Lab creates a living experiment in which everyone becomes an investigator

iane Pataki knows a few things about an interdisciplinary approach to science. A trained ecologist she is as much at home as a fellow in the American Geophysical Union as she in a traditional biology department largely founded on the study of botanicals and mammals on both the taxonomic and molecular/cellular levels.

While currently a faculty member in the School of Biological Sciences as well as Associate Dean of Research in the College of Science, she is also the Associate Director of the U’s Center for Ecological Planning & Design in the College of Architecture + Planning. A further extension of her expertise and interest is in northern Utah where she holds an adjunct appointment in the Ecology Center and the Department of Landscape Architecture & Environmental Planning at Utah State University.

Emblematic of that outreach is one of Pataki’s current projects, the Landscape Lab, the construction of which begins the summer of 2019. The Lab is part of the U’s Center for Ecological Planning & Design, and will restore ecological and social functions to a portion of the Red Butte Creek watershed in the University’s Research Park. This in turn will increase access to recreational space for occupants of the nearby Williams Building, the campus community, and the public as a whole. The Lab will also test research questions about urban stream restoration, urban runoff management, hydrology, use of public space, and more.

Whether it’s developing an integrated socio-ecohydrologic framework to facilitate the understanding of and transitions to sustainable water systems, or giving the keynote address at

Central to the installation of the Landscape Lab is the hope of answering a persistent question of Pataki’s and other urban ecologists: Since eighty percent of Americans now live in an

Diane Pataki was recently named Associate Vice President of Research at the U.

the Atmospheric Sciences Symposium at UC Berkeley, Pataki, a PhD graduate from the Duke University Nicholas School of Environment, sees her academic role as a convener of seemingly divergent sectors in pursuit of understanding the emergence of sustainable ecological practices. Little wonder then that her research of late in urban ecology has quickly bled into the kind of community outreach consistent with the “One U” concept, the idea that the University is as much “for” Utah as it is “of” Utah.

urban habitat, exactly what is that habitat? Furthermore, how does this habitat inform both the scientifically-based notion of nature as well as the socially-based notion of culture—an intersection where a species is both radically shaped and where it shapes its (our) environment? “This is a big project,” explains Pataki. “It’s about turning [this part of ] campus into a living lab, an unexploited place for us to do research and for learning.” The Lab is a component of a larger seventy-page plan to revitalize the entire corridor along the campus stretch of Red Butte Creek. The overall goal is to transform the riparian corridor from a neglected, underused area of campus to an asset for teaching, research, and community engagement. The Landscape Lab is intended to be both a scientific experiment and a beautiful garden space designed by local consultants VODALandscape + Planning. One of the experiments to be conducted involves bio-swales, patches of land designed to infiltrate rather than repel stormwater that would otherwise contribute to high stream flows, pollution loads, and erosion of Red Butte Creek. In water-limited places, such as the high desert of Utah, sustainable water management infiltrates storm water into the soil where it replenishes local life cycles. Eventually, artists, philosophers and other abstract thinkers will also find a home and a “lab” in this green space of an urban garden. “We are creating a scientific experiment writ large, as it were,” Pataki says, “that’s beautiful on top.” The socio-ecological Landscape Lab is in part an attempt to put science underneath the concurrent public discourse between the empirical (rational) and equally important valuebased discourses about habitats. In this sense, the Lab will ideally function as a catalyst, bringing the two halves of our sometimes contentious and emotional discourse over land management together. This exertion of communicative power happens by bringing diverse peoples into the living lab. At the same time, in ecological studies it’s critical, but still relatively

“We are creating a scientific experiment writ large, as it were, that’s beautiful on top.”

rare, to directly measure the environmental benefits and costs of urban landscapes. The Pataki Lab uses a variety of methods to measure urban plant and soil processes and translate these processes into costs and benefits of interest to urban residents, managers, and policy-makers.

Rendering of The Landscape Lab courtesy of VODA Landcape + Planning

In addition to the Landscape Lab, Pataki and her partners have a number of ongoing projects focusing on the role of different plant species, landscape types, and land cover in influencing urban climate, water resources, atmospheric composition, and greenhouse gas emissions. “We are investigating these processes in Los Angeles, California and Salt Lake City,” writes Pataki in her research statement, “with direct measurements of plant physiology, ecosystem water balance, soil nutrient cycling, and greenhouse gases.” “Science is about working with the unknowns,” Pataki says. The scientific method requires testing theories and hypotheses about the consequences of designing and managing urban nature in different ways. “Cities [and suburban areas] are really complicated ecosystems,” she continues. “We don’t yet know how to build urban nature that benefits everyone.” Enlisting the expertise of professionals who represent different disciplines as well as stakeholders in our environment (that is, all of us) means allowing for an urban garden and landscape that is democratized. Basic ecological science is a major underpinning to that broader conversation, a seamless joining of Pataki’s research and community outreach.

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The Crimson Laureate Society

he Crimson Laureate Society is a group of people dedicated to the advancement of science and biology at the University of Utah. Together with the U’s latest ongoing IMAGINE NEW HEIGHTS campaign, your participation underscores the U’s growing culture of philanthropy and the promise of the University to continue to rise.

The School of Biological Sciences invites you to join this esteemed group of citizen-scientists, alumni and friends. A gift of $100 or more will automatically enlist you as a member of the Crimson Laureate Society, and will advance our education and research mission. As a member you’re entitled to invitations to special events and tokens of appreciation from the College. To join the Crimson Laureate Society, visit biology.utah.edu/giving Your gift in whatever amount can be designated to the project or initiative of your choice. Again, membership in the Crimson Laureate Society begins at $100.

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