OUR DNA Fall--2022

Challenge

of Our Time

When I stepped into the role of Director of the School of Biological Sciences, I was fortunate to build upon the successful leadership of outgoing co-directors Leslie Sieburth and Neil Vickers. Despite the challenge of filling their four rather large shoes, the School was in a strong place with seven exciting new faculty, firm links between teaching and research, enhanced unity across the wide range of disciplines we gather under the umbrella of “biology,” and an official end to the pandemic.

As we know, however, the virus SARS-CoV-2 and the disease it causes, COVID-19, are still very much with us. The challenges of the pandemic have not only taught us much about the resilience and fragility of our society but reminded everyone of the importance of biology in our lives. The rise of new variants is a living illustration of evolution in action; the overnight identification and sequencing of the virus and resulting PCR testing shows the power of modern genetic methods; the vaccines illustrate both the power of new technologies and the complexity of the immune system; and the spread of the disease highlights the importance of mathematical modeling for understanding, prediction, and control.

The origins of the virus from an animal host exemplify what is perhaps the central challenge of our times—the link between environmental change and human health. As we alter the planet, we interact with novel species and transform the way that existing species interact with each other and with us. The warming climate allows mosquitos that transmit tropical diseases to spread to new areas.

But new diseases are just one example of the challenges that global environmental change poses for human health. Earlier spring and later fall is extending the allergy season. Heat and drought promote wildfires that pollute the summer air, harm our lungs, and drive people indoors. Excessive time spent indoors creates psychological stresses already exacerbated by disease lockdowns and concerns about the future of the planet.

Faced by these pragmatic problems, how does basic science contribute to taking on this central challenge of our times? I see four key roles for SBS.

First, basic research makes fundamental discoveries with unexpected consequences. The recent “Golden Goose” award to Distinguished Professor Toto Olivera and his lab is a perfect example—the study of some obscure predatory snails has advanced our understanding of neurons and led to development and patenting of new non-addictive painkillers.

Second, in the hands of SBS researchers, basic research and applied research go hand-in-hand. Understanding how plants respond to stress opens the door to breeding drought-tolerant plants. Understanding how mosquitos interact with bacteria reveals ways to control these disease vectors.

Third, as one of the largest majors on campus, SBS plays a central role in training the next generation of students in the knowledge and ways of critical thinking to find and implement solutions.

Finally, SBS provides the link between the world-class expertise in environmental science and health sciences of which the University is justly proud. The new Wilkes Center for Climate Science and Policy, led by SBS Associate Professor Bill Anderegg, opens up myriad opportunities for collaboration with our world class medical school.

As I like to say, we had two tools to fight the pandemic, our brains and our immune systems. Our brains are the only tool we have to address the challenges of our times, and it is the collective power of the thinking that characterizes the work in the School of Biological Sciences that gives me the greatest hope for the future.

Sincerely,

Fred Adler Professor, Director

Fred Adler

Seeing the

Chan Yul Yoo Light

You may have heard that trees communicate, but did you know that plants have eyes?

“Just as we see the world by our eyes, plants see light with photoreceptors to control growth and development throughout their entire life cycle,” says Assistant Professor Chan Yul Yoo who arrived at the School of Biological Sciences this year. (His wife Heejin Yoo is also a new assistant professor at SBS with her own lab. You can read a research profile of her in our Spring 2022 issue of Our DNA.)

While you may be familiar with Charles Darwin’s work on evolution, he together with his son Francis Darwin also studied that plants can sense and bend towards the light from a book called The Power of Movement in Plants in 1880. Since then, molecular genetics and cell biology approaches have led to the identification of a suite of photoreceptors in plants and the discovery of photobody in the nucleus.

Photobodies are plant-specific biomolecular condensates that contain photoreceptors for sensing light and regulating almost every facet

of plant growth and development including chloroplast biogenesis. Phase separation behavior of photobodies have become an urgent field of scientific inquiry to help the earth continue to green through photosynthesis and to augment crop species for a hungry world.

“Our lab is interested in understanding fundamental functions of photobodies in reprogramming plant growth, development, and chloroplast biogenesis,” Yoo says. As our planet continues to encounter global climate changes including warming and drought, the greening of the earth through plant life is critical for cooling the atmosphere by transpiration and holding ground water in the soil. Yoo’s lab focuses, in particular, on the role of photobodies as developmental and environmental sensors in nucleus-chloroplast communication to orchestrate transcriptional regulation in nuclear and chloroplast (green plastid) genomes.

That may be a mouthful of plant biology vocabulary, but Yoo has, since his arrival in SBS, been here to help us understand his work. The backstory to that work lies in evolution when the earliest photosynthetic organisms were single cell cyanobacterium containing chlorophyll, the green pigment used to absorb light energy

The eye of green plants: phytochrome B photobodies fused with green fluorescent protein in every nucleus (blue, DAPI staining). Photo credit: Chan Yul Yoo

and turning sunlight into food while expelling oxygen as a waste product and creating our breathable atmosphere for all living organisms including human. For billions of years these organisms remained under water in their colonies… and then, 500 million years ago, algae emerged. Algae featured chloroplasts where photosynthesis takes place.

Fast forward to the emergence of genomics when scientists learned that it requires two discrete sets of genomes—one found in the chloroplast of a plant cell, the other in its nucleus—to fix the CO2 in a way to produce sugar and oxygen, the magic of photosynthesis.

“Plant biologists have known this for a while,” says Yoo about the symbiotic genomes. As a post-doctoral researcher he sometimes despaired that “all things” in plant biology had already “been discussed, found, and otherwise saturated.” So what’s a post-doc to do?

It turns out that Yoo had despaired prematurely.

Seeing the Light

Plants like Arabidopsis, a well-established model species, feature chloroplasts that have evolved over time with territorial stressors: drought, high irradiance sunlight, fresh vs. salt water. Over time many genes of the plant have been lost or have migrated from the chloroplast to the cell’s nucleus.

We know that light triggers photosynthesis through photoreceptors which control growth and development in a plant. “Phytochromes,” for example, are photoreceptors that sense the red/far-red in the spectrum of light. Without these receptors, plants do not turn green and show the photomorphogenic phenotypes.

Once phytochromes sense red light, one of the earliest cellular events is the relocation of phytochromes from the cytoplasm of the cell to the nucleus whereby they form membrane-less organelles called photobodies, the “eyes” of the plant. These subnuclear foci “see” the light which in turn triggers the growth of a plant toward that those life-sustaining waves and the greening we relate to a healthy plant.

The greening (chloroplast biogenesis) requires coordinated nuclear and plastidial (chloroplast) gene expression. After all, the two sets of genes are each held within their own respective membranes. Clearly, communication of some kind is happening between the two organelles. But how? And what exactly is it?

It turns out that light-activated photobodies in the nucleus activate the assembly of bacterial-like multi-subunit RNA polymerase called PEP in chloroplasts. Using forward genetic screening, Yoo discovered albino mutants with defects of photobody and PEP assembly.

This was the research space the young scientist pivoted to during his post-doc malaise, and his research led to exciting discoveries about a novel framework of anterograde or nucleus-to-chloroplast signaling pathway. That pathway, again, through some kind of communication, is still under

investigation. It’s what links photoreceptors-containing biomolecular condensates—the photobody eyes—in the nucleus to the chloroplast biogenesis.

Yoo lab’s current research is trying to identify this mysterious signaling molecule in nucleus-chloroplast communication. In addition, the lab is interested in uncovering mechanisms by which plants regulate the formation of photobodies via phase separation in response to environmental changes. Ultimately, Yoo lab expects to develop climate-resilient greener plants to make our planet green.

A Global Journey with Dr. “House”

The research journey for Dr. Yoo was a globe-trotting one. After securing his bachelor’s degree in his native South Korea, he earned his PhD in Horticultural Science at Purdue University in 2011. There he worked on plant molecular genetics involved in abiotic stress adaptation. His research was focused on understanding the molecular, developmental, and physiological mechanisms of acclimation and adaptation in various environmental stresses including high temperature and drought stresses. Then, Chan Yul joined to Dr. Meng Chen’s lab at Duke University as a postdoctoral associate and followed the lab’s move to the University of California Riverside to study light, one of the most important environmental signals for the life of plants.

Along the way he also picked up research tactics from popular culture, specifically the TV series House, and his use of what the good doctor (albeit, one with a notoriously scabrous bedside manner) calls “differential diagnosis:” when a patient’s symptoms match more than one condition and additional tests are necessary before making an accurate diagnosis. For Yoo, the “patient” is the tall and albino plant that is unable to green and eventually dies, and he wants to cure that. “There are possible reasons for that in many directions,” he explains. “You have to look at many different possibilities at the same time.”

For a plant biologist concerned with reprogramming plant growth and development, gene-editing has proved useful in “knocking out” multiple Phytochrome-Interacting transcription Factors (PIFs). Can we cure albino plants by removing of PIFs in the nucleus? The answer it turns out is yes. But the point is, you can’t just focus on the chloroplast since it’s also a nuclear event.

It’s also an event that requires communication between the two genomes, one each in the nucleus of the plant cell and in the chloroplast. This communication is what is still partially eluding Yoo and his team, but in the lab, differential diagnosis continues. Their work discovered another mutant at the same time as the publication of a paper in 2019. “We thought at the time, ‘let’s cure this mutant as well!’” says Yoo. But that didn’t work as there are two separate functions in the same signaling pathway.

It’s all part of the recursive and provisional conclusions of inquiry in Chan Yul Yoo’s new lab to help make plants—from the grass on a PGA golf course to crop plants like dwarf maize—“see” better, develop better, and keep our planet green.

The Chan Yul Yoo lab is even dreaming about growing plants in space or turning the red planet Mars green.

Sarmishta Diraviam Kannan, HBS’17

“A New Dream is Already Forming”

For Sarmishta Diraviam Kannan, HBS’17, the journey to her “dream school”—the University’s School of Medicine— spanned about 25 years and some 8,780 miles.

Sarmishta was born in Tamil Nadu, India, which is located on the southern tip of the Indian sub-continent. In addition to the long history of the Tamil people, Tamil Nadu is famous for its temples, festivals, and celebration of the arts.

When Sarmishta was just nine years old, her family immigrated to the United States. They settled in Boston, where her father worked for GE Healthcare. In 2008, the family moved to Salt

Lake City, near the corporate headquarters of GE Healthcare, while her father continued his career with the company.

Sarmishta, who was then 12 years old and in junior high school, was still mastering English as a second language and adjusting to social norms and public education systems in America.

It was a difficult time for Sarmishta, but her “dream” was beginning to form.

Sarmishta graduated from Hillcrest High School, in Midvale, in 2013 with the International Baccalaureate (IB) diploma. “The IB diploma is a rigorous program, and I was the only one to take the higher-level courses in all three sciences of physics, chemistry and biology,” says Sarmishta. “It was through the IB program that I found my passion in the sciences, especially biological sciences, and completing the IB program prepared me well for college.”

Sarmishta decided to attend the U as an undergraduate because of the abundance of research opportunities and the Honors degree option in Biology which gave her the chance to perform long-term research that culminated with an Undergraduate Thesis. Plus, it put her in close proximity to the School of Medicine.

The “dream” was clear now and within reach.

“The Honors thesis requires involvement in research that finishes with writing a paper on a particular research project. That experience was valuable to me as I got the opportunity to be involved in a research project from start to finish,” says Sarmishta. She worked with Dr. Kevin Jones at the Huntsman Cancer Institute to help discover the roles that lysosomes and autophagy play in alveolar soft parts sarcoma, clear cell sarcoma, and synovial sarcoma.

“In the Jones lab, it was fascinating for me to see how researchers used experimental data to understand cancer biology. So, I decided to pursue sarcoma research for my thesis,” says Sarmishta. “I investigated the hypothesis that Alveolar Soft Parts Sarcoma (ASPS) and Clear Cell Sarcoma (CCS) morphology is attributed to lysosomes and that these cancers up-regulate autophagy genes using autophagy as a survival mechanism.”

“I learned to design investigations and troubleshoot various lab protocols to gather data and test the hypothesis,” she continues. “Critically analyzing the data supported the hypothesis that ASPS and CCS contain abundant autophagic lysosomes. However, it raised further questions indicating more research was necessary to better understand autophagy’s role in ASPS and CCS. Writing my thesis taught me to build an evidence-based argument based on my data, critically analyze the work of others, synthesize new ideas for further research, and effectively communicate complex topics.”

Her thesis abstract was published in the 2016 University of Utah Undergraduate Research Journal. She also presented her thesis to Utah legislators at the Research on Capitol Hill event in 2017 and at Undergraduate Research Symposiums in 2016 and 2017.

After graduating with an Honors degree in Biology, she continued to work in the Jones lab as a full-time Lab Technician before starting medical school. She worked on various projects including writing a review manuscript on sarcomagenesis, titled Genetic Drivers and Cells of Origin in Sarcomagenesis, which was published in early 2021 in the Journal of Pathology.

She also worked on a project that focused on modeling synovial sarcoma metastasis in mouse models. Sarmishta was listed as a co-author on that paper and was published in the Journal of Experimental Medicine.

In the meantime, Sarmishta applied to the School of Medicine in 2019 and in 2020 and was accepted in 2020.

Finally, her “dream” was realized.

Sarmishta will soon complete the second year of the MD program at the University’s School of Medicine. “It has been a very fulfilling experience so far!” she says. “I am grateful to have the opportunity to follow my passion, learn about the human body, help and support people going through healthcare challenges. I am excited to start my clinical years where I get to rotate through various specialties in the hospital and apply all the knowledge I have been learning to patient care.”

In addition to school, she enjoys reading, painting, watching movies, and singing. In fact, Sarmishta is a classically-trained Carnatic singer. Carnatic music is a traditional system of music from India that provides a nearly limitless array of melodic patterns. It emphasizes vocal performance.

“I started singing when I was five and my parents enrolled me in Carnatic music classes in India. I continued my training after moving to the United States,” says Sarmishta.

“I perform publicly at the local Hindu Temple and at Indian festivals. One of my most cherished experiences was performing a Hindu song at the 6th Parliament of World Religions event, that was held in Salt Lake City.”

Sarmishta is scheduled to complete the MD program in 2024 about which she says,

“A new dream is already forming.”

“I am grateful to have the opportunity to follow my passion, learn about the human body, help and support people going through healthcare challenges.”

A Best Case Scenario… That Wasn’t Planned

A crackerjack team of U of U undergrads works with principal investigator Ben Myers to break open a decades-old biological mystery

Corvin Arveseth, BS’21, can’t remember when he wasn’t fascinated by science and biology. So, when he came to the University of Utah and declared his majors in biology and biochemistry, he knew he wanted hands-on experience in research. “I didn’t know anything [about the] Hedgehog (Hh) signaling [pathway] until I read an advertisement put out by Ben Myers, [principal investigator at Huntsman Cancer Institute and assistant professor of oncological sciences at the University of Utah] in a biology department newsletter looking for undergraduate researchers,” he says. “After reading some background information and

The Ben Myers Lab: Corvin Arveseth, Nate Iverson, Isaac Nelson, Ben Meyers (Principal Investigator), Will Steiner, Madison “Maddie” Walker

meeting with Ben about the Hh pathway, I became intrigued with the work being done in his lab.”

The Hh pathway he’s referring to is akin to a master set of instructions for animal development and regeneration. It controls the formation of nearly every organ in the human body. Signaling pathways like Hh serve as molecular “telephone wires” from the cell surface to the nucleus. When cells in our bodies communicate with one another, signals are relayed along these molecular telephone wires, turning on expression of genes involved in growth, differentiation, or in some cases, skin and brain cancers.

The Hh pathway got its unusual name from decades-old genetic studies in fruit flies, where mutations in critical developmental genes led the flies to take on a bristly hedgehog-like appearance. However, versions of the Hh pathway operate throughout the animal kingdom, controlling development, stem cell biology, and cancer in many different contexts.

But even after many years of effort by labs all over the world, surprisingly little was known about how the Hh pathway actually works at a molecular level. Scientists knew that the signals conveyed by these molecular telephone wires were fundamental to human development and disease, but they didn’t know what the signals were, or how they were transmitted intracellularly. Consequently, health researchers’ ability to control Hh signaling in many diseases including cancer had been limited.

So, this is a story not just about a seemingly intractable research question, which is de rigeur in scientific circles, but how a team of largely undergraduate students in a four-yearold lab worked together under enormous odds to shake loose that answer. Myers says that it was because of inexperience, not in spite of it, that the undergraduates in his lab were able to make these discoveries. These students’ fresh, undaunted determination to scientific inquiry, combined with a lack of preconceived notions and a willingness to learn, were key factors that enabled their groundbreaking discoveries.

Two papers, both with U undergraduates as first or co-first authors, were the gratifying result.

Mysterious pathways

When Myers first set up his lab at the U in 2018, the key molecule in the Hh pathway that grabbed his attention was SMOOTHENED (SMO), a so-called “transmembrane protein” that spans across the cell membrane from the outside to the interior. SMO was known to be critical for transmitting signals from the cell surface to the nucleus. But what were the five or six steps between receiving the message and turning on gene expression? There was a “major disconnection about how this worked,” says Myers.

The twenty-five-year-old mystery was indeed tantalizing. It was “this interesting mystery coupled with the importance of Hh function,” says Arveseth, “in developmental and cancer biology [which] hooked me right away.”

Spearheading the project

Arveseth was the point of the spear for this project begun at the beginning of his sophomore year. But there were many others on the team, all of whom are “both incredibly smart, and also very kind and a lot of fun to work with,” according to Myers. This includes Nate Iverson, a third year chemistry major with an interest in cellular signaling. “Having HCI in close connection with the University gave me greater access to research possibilities, and I was able to find an opening in the Myers lab studying Hh signal transduction.”

And then there was biology major Isaac Nelson, who worked tirelessly to produce a freezer full of carefully prepared, purified fragments of SMO for biochemical studies, only to hit a brick wall when he and Myers were unable to formulate a good hypothesis to drive an experiment. “It was only after starting up an international collaboration,” says Myers, “that the critical experiments snapped into view for us.” This led Nelson to send his samples to one of the lab’s new collaborators in Germany, and they used his samples to try an experiment that worked right away. In the midst of a raging pandemic, Nelson’s purified proteins helped to launch a new and entirely unexpected phase of the project, expanding the collaboration to include other scientists around the world.

“It was another scenario,” says Myers, “where everyone worked well together.”

Recent graduate Madison “Madi” Walker, BS’21, with a cell and molecular emphasis, was also part of the team. She is still working in the Myers lab studying another critical aspect of SMO signaling, namely the interaction between SMO and the enzyme G protein-coupled receptor kinase 2. Earlier, former undergraduate Jacob Capener, BS’20, assisted in the work.

Ben Meyers with hedgehog

Another critical member of the Myers lab team is Will Steiner, BS’21, who is currently collaborating with Arveseth and Nelson to purify SMO in complex with its binding partners in order to work out their atomic structures. He became interested in this area of research after taking the cell biology and biochemistry course at the U. “Biochemistry was particularly compelling and got me excited about the chemical reactions behind human physiology,” he says.

It starts in the classroom

Rigorous courses were critical in preparing Myers’ undergraduate team for the hands-on research that led to their remarkable findings in the lab. He has nothing but kudos for the U’s curriculum. “Coursework before the lab experience [for undergraduate researchers] was very, very good here. In general, I’ve been lucky to attract motivated and curious students to my lab. They are inspired to push the research forward. They are all up to the challenge. And they have a great esprit de corps. They all work incredibly well together as a team to drive the science forward.”

of two discovery-laden papers, is that their remarkable findings stemmed from the initial naïve view that the SMO protein didn’t fit the mold of other proteins as was previously assumed. He and Arveseth took a guess that SMO might be directly coupled to a critical intracellular signaling molecule called PKA. This was a rather wild idea, since there were few if any examples of transmembrane proteins that directly interacted with PKA. “It was a guess, how it might work, and a couple of months later: big discovery. Our initial guess was on the right track. There was a whole new unexpected thing going on but that made sense.”

Though early on the team suspected what they had discovered was important, “we didn’t know if we had a full explanation of how the system worked. We weren’t sure if it was the main event or an auxiliary event.” In the first paper, published in the journal PLOS Biology last year, they explained that: what they thought they knew, and what they weren’t sure about… yet.

But it was only after the pandemic was in full force that the team pivoted to the second exciting phase of the project, expanding to include Susan Taylor’s lab at the University of California, San Diego, one of the world’s foremost authorities on the PKA molecule the Myers team had implicated in their research.

Taylor and her colleagues had a critical insight regarding the SMO-PKA interaction which eventually formed the basis of a second manuscript, recently published in Nature Structural and Molecular Biology. “It is a truly remarkable and inspiring collaboration that continues to this day, and I am so proud of how everybody was able to join forces and overcome so many obstacles created by the COVID-19 pandemic,” says Myers. And his team is anticipating that even more exciting discoveries are on the horizon. Eventually, this work may lead to better drugs to treat some of the diseases that result from aberrant Hh signaling, including various skin and brain cancers.

That kind of correlated teamwork was not necessarily easy to enact under the circumstances. “Fortunately, we were able to finish the last key experiment of the first paper,” says Myers, in March 2020, just before the pandemic started to take hold and shut lab work down. He’s always believed that having undergraduates get a taste of cutting-edge research is important. They “shouldn’t have to work on something trivial… What’s exciting about science is to push the boundaries.”

And yes, for Myers and the other senior members of his lab, including graduate students Danielle Hedeen and Aram Centeno, lab manager Ju-Fen Zhu, and former lab technician John Happ, “you have to be committed to helping everybody in your lab, even if they’re neophytes.” Clearly it’s been worth it. “And being a little bit of a neophyte is good,” he says, “because you don’t talk yourself out of doing experiments that are simple, unorthodox.”

Asking the right questions

What Myers is trying to say, and seems to have proven over the course of the past three years and now the publication

In all, with the resulting two papers, the project turned out to be a “best case scenario that wasn’t planned,” and a lesson of how important it is to keep an open mind, which often leads to big discoveries.

Success is never final, however. And Arveseth, recipient of no less than ten scholarships and awards during his sojourn at the U, is now enrolled in the MD/PhD program at the Washington University in St. Louis, where he will focus on hematology and oncology. His colleagues are also pursuing their academic and research careers full-steam ahead. They, along with their mentor Ben Myers, are a testament to the notion that persistence in knowledge gathering pays off but that it must be paired and even driven by a relentlessly open mind.

Concludes Myers, “To be honest, it comes down to the willingness to try new things and to have the ability to work together as a team. In reality, this would have been way too much for any individual scientist, even a highly trained one, to do alone.”

You can follow Meyers and his lab on Twitter @Myers_lab

“Being a little bit of a neophyte is good, because you don’t talk yourself out of doing experiments that are simple, unorthodox.”

The Wilkes Center for Climate Science and Policy

The geography that makes Utah unique—red rock deserts, greatest snow on Earth, cities amidst natural beauty—also makes us vulnerable to one of the biggest challenges of our time: climate change.

Climate change can drive or exacerbate severe drought, wildfires, air pollution, water scarcity, and disappearing snowpack. Luckily, the University of Utah has a deep pool of experts who use the campus location as a living laboratory to address these immense challenges.

A generous $20 million gift from Clay and Marie Wilkes will leverage the U’s location and interdisciplinary knowledge to create the Wilkes Center for Climate Science and Policy. William (Bill) Anderegg, associate professor in the School of Biological Sciences, is the inaugural director of the Wilkes Center, which will be housed in the College of Science. Eventually, the Center will move to the new Applied Science Building currently under construction south of the Crocker Science Center in the soonto-be-retrofitted and augmented Stewart Building.

“One example that we’re getting off the ground quite quickly is the Great Salt Lake Strike Team,” says Anderegg of the Center and its myriad partners at the U, governmental and other higher education partners, “it’s a short-term, focused

team to synthesize key areas about the threatened Great Salt Lake and what can be done about it, and to provide that information to the legislators before the next legislative session.”

Peter Trapa, Dean of the College of Science, which recently merged with the College of Mines & Earth Sciences, another critical partner in this venture says, “We envision that the Wilkes Center will distinguish itself as a partner, or in some cases, the go-to place for scientific information to advise decision-makers, especially in certain domains around air, fire, and water. The Wilkes Center will leverage Utah’s unique geography and its positioning on the front edge of climate change.”

William “Bill” Anderegg

U President Taylor Randall with donor Clay Wilkes at the announcement of new center.

Visualizing the Infinitesimal

Even before Andreas Vesalius (1514–1564) first put pen to paper to draw the human form in anatomical detail, scientists have illustrated their findings, not only to share information but to find greater footing on the terrain we call biology: the science of life.

These models have taken on new urgency with the advent of cell biology, where subjects are even smaller than cells. “This is an invisible space,” Janet Iwasa, molecular visualization expert and Assistant Professor of Biochemistry at the U, reminds us. “Most molecules are smaller than the wavelength of light. These things are moving at a time scale that is not intuitive. When the study objects are so foreign, you have to rely on creative approaches to describe them.”

For Iwasa, those approaches involve scientifically accurate digital animations which have cracked open an entirely new way of viewing diverse molecular and cellular processes. Information-rich and visually compelling visualizations that capture current understanding is what this classically-trained biologist has made a name for herself with.

The need for reconsideration of the visual language that renders the invisible became urgent after a 2009 publication in Science of a much-cited article. The seminal paper posited that cellular structures called P granules are liquid droplets, and that they specify the future germline in a developing embryo through controlled dissolution and condensation. This paper ignited one of the hottest “trends” in cell biology—the study of biological liquid condensates—and earned the lead authors numerous prizes, including, most recently, the prestigious Breakthrough Prize.

For Ofer Rog, Assistant Professor and Mario Capecchi Chair in the School of Biological Sciences, this revelation completely revised the interpretation of his experiments, but also brought with it “whole sets of biological issues.” The existence

of crowding in the cell was one of them. No longer could he try to reduce the behavior of the chromosomes he was studying to properties of single molecules that make them up. “Rather,” says Rog, “we had to understand them as collective or ‘emergent’ behavior.”

With this new understanding, Rog felt “stuck” in his teaching and research with an old graphical language which “was really great for depicting things that are best understood as single objects, but not so great to describe how big clusters work together, to describe how molecules interact with each other much more loosely and much more dynamically.” The recognition of the flexibility and dynamics of cellular components led to the impulse to better honor that complexity graphically.

“I started looking at papers, and how uniform they were,” Rog says. “Papers that were clearly written with a lot of careful attention to details, with exquisite experiments and data, were using graphical models that were very simplistic, inadequate to really capture… our new understandings about biology. I started wondering, ‘How did people solve this in the past? Who should we talk to?’ It wasn’t super clear. So I went and talked to Janet.”

Powerful Renderings

They say the most dangerous thing one can do is to introduce one person to another. It’s a tongue-in-cheek caution, reminding us how conversations, then collaborations, then innovations start. So it was with Iwasa’s animation expertise which, as part of her Animation Lab at the University of Utah, has already animated many subjects, including the life-cycles of HIV and SARS-CoV-2. Now the lab is pairing its expertise with Rog’s condensate research.

“We have a lot of people, like Ofer,” says Iwasa, “who are educators and who have been using our animations for their

Illustration credit: Margot Riggi, PhD, Animation Lab, Postdoctoral Fellow

courses. Condensate research is so new, compared to other big concepts in biology, that a lot of textbooks don’t even cover it. So, having some visual materials for educators who need an intuitive way to introduce these ideas to students was something we were thinking about.” Iwasa’s team had already interviewed undergraduate instructors to find out how they were teaching about condensates and what kinds of challenges they were facing.

And how were professors like Rog teaching about this new paradigm? Not easily, it turns out. The terrain was daunting. Intrigued, the Animation Lab began collaborating with Rog and other cell biologists to better illustrate condensates. “This new paradigm,” writes Rog and Iwasa of their collaboration, challenges “the 20th century textbook view of cellular compartmentalization.” Condensates, she says, seem to play important roles in cells’ normal functioning and in disease, and, naturally, these concepts are now making their way into undergraduate classrooms.

Metaphors can be dangerous

Introducing two people is not the only dangerous thing to happen out there. There are implications of and uses for blending digital animation with biology and other sciences: representations—visual or verbal—are essential tools, but at the same time impose biases. Because of simplification, “metaphors can be dangerous,” Iwasa concedes. “People don’t know how far they can carry them on a molecular level.”

The “language” of graphic representations, according to Rog, have tended to focus on single atomized cell components, and also incorporated implicit assumptions taken from our daily lives.

Iwasa agrees. Imagining the molecular space is “unintuitive, since it is unlike the air- and gravity-filled world we live in. What does a molecule experience being inside the cell? It’s just very different and hard to conceive. Some metaphors can be misleading. For example, there are proteins in the cell that move using a walking-like motion. Says Rog, “We walk in air, but when a molecule “walks,’ it’s the equivalent of us walking through Jell-O—”

“—Or walking in one of those children’s ball pits,” interjects Iwasa. “Except the balls are as big as you are, and you’re constantly bumping into everything, having to push things around.” The constant collisions, the extreme crowding: biologists know about these qualities, but because they don’t often depict that space, “it’s easy to forget and not to consider that, and that influences the types of experiments and the types of models we create.”

Illustrations did occasionally remind biologists of the crowded environment that occupies their objects of study. David Goodsell, a structural biologist and watercolor artist at the Scripps Research Institute in San Diego, is famous for his colorful illustrations of the interior of cells. These paintings are based on state-of-the-art knowledge of what is in the cell–what molecules exist in different sub-cellular compartments and what structures each of them adopts–but also capture the incredible complexity of the cell and, crucially, its crowdedness.

The symposium “Re-Imagining a Cellular Space Occupied by Condensates” was held on the U campus and in Park City Oct. 11–13, hosted by Ofer Rog and Janet Iwasa. The objective of the gathering was to “daylight” how biologists represent a subcellular world in enabling as well as disabling ways, seeking “to build a community that will construct a visual language and new tools that will accurately capture the complexity of molecular condensates.

Participants included experts from diverse disciplines: about one-third of the participants were biologists, actively engaged in condensate research; one-third were visualization and computation specialists—like watercolorist David Goodsell, mentioned above—but also modeling experts, data visualization specialists, and molecular animators.

The final one-third attended from fields not commonly engaged with molecular biology but that have long been thinking about space and ways to represent it, including software and virtual reality developers and academics in architecture and history.

The new science of condensates relies on crowding for the ability of cellular structures to come together and fall apart. Rog, excitedly, returns to the human model and talks about “a thousand objects, like humans, in a crowded subway station, loosely associated” which, nevertheless, remain discrete individuals. How do those individuals behave separately? And how does that behavior change when they function as a collective?

New visual language and recent technological development promise to do a better job of depicting such complexity. Such representations continue to inform scientific discourse, as startling and revealing as 16th Century drawings brought to life through Vesalius’s magisterial bodies-in-motion.

To view animations and other illustrations of the subcellular world, including of the condensates being studied in the Rog Lab, visit animationlab.utah.edu

Meet your new Anatomy Professor Jon Groot

“I took two years off following my bachelor’s in education,” says Jon Groot, PhD. “All I knew was that I wanted to learn more. [I had] no end point in mind. I was just going for what interested me.” The Salt Lake City native moved to Seattle and spent four months in Asia, including Japan and Tibet. He studied to be an EMT.

That’s when he walked into Mark Nielsen’s anatomy class, almost as a one-off, at the School of Biological Sciences. The unique lecture-followed-by-cadaverlab experience categorically entranced him. He served as an apprentice TA for one semester, then as a mentor TA for two years, helping to train the apprentices who rotate through lab stations in small groups, each station featuring a different prosection—a dissection of a cadaver or a cadaver component for purposes of instruction. Students are not just looking at line art memorized on a page when they take anatomy at SBS. Instead, through the station rotations they hold the human body and its parts, they touch and explore it.

Groot remembers sitting in class and fantasizing about being Nielsen. “I want to do what he’s doing,” he thought. Little did he know that even after leaving for six years of graduate work, culminating in both a Master’s and a PhD, it was Nielsen to whom Groot routinely returned for mentorship. “At every level of my education,” he says, “Mark invoked excitement in human anatomy, changed my life and changed my life direction. I never honestly believed that I would do it [take over from Mark],” he says, shaking his head.

And yet here he is.

As of July 1, Groot, father of two, is the new anatomy professor at the School where hundreds of pre-professional undergraduates will re-live his own experience years ago when he sat in class and moved from station to station, scalpel in hand, gloved and glowing about the sheer joy of explaining to others the ultimate machine: the human body.

Perhaps it’s because his bachelor’s is in pedagogy, but it did not escape Groot that his enduring mentor “was not up there [just] to teach anatomy but to teach his students how to learn. He seamlessly goes into being a mentor from being a teacher or professor.” He sees Mark as the ultimate “growth giant,” a teacher first regardless of the subject or content.

The serendipity of his path—from Alta High School in Sandy where Groots lived in a family of teachers and school counselors to his bachelor’s at the U, and from his gap years in Asia and his virtual stumbling into Nielsen’s lab—led to a master’s in Exercise & Physiology which eventually morphed into PhD work. This aspiration pushed him into research and publishing that was “intense” even “brutal” compared to if he had taken a less condensed track.

Following completion of his doctorate in 2015, Groot threaded his way through half a dozen adjunct appointments before being asked to teach at the U in Health Kinesiology and Recreation (now Health and Kinesiology).

After his career there but before being tapped as the new anatomy teacher at U Biology he was Assistant Professor (Lecturer) in Health and Kinesiology where he directed the Human Performance Lab for six years. He taught all the undergraduate students in those labs—the kinesiology course alone numbered 140 students per section. On top of the teaching load, more serious research awaited Groot like one of his gnarly opponents in Wado Ryu karate, in which Groot has become a fourth-degree black belt (of course) as well as a Sensei… another term in the sport for “master teacher.”

Needless to say, Groot likes a challenge and to keep busy, and his refrain is always this: I love to teach. Among other innovations, he hopes to increase funding for TAs in the anatomy lab while also offering a new course next fall: Applied Musculoskeletal Anatomy in which joints and the study of bio-mechanics will help future physical therapists and doctors assess human movement, including errors, and to correct them without surgery.

Mark Nielsen continues to be a north star to his heir apparent as Groot picks up the reins of a nationally-recognized program and attempts to put his own thumbprint on it. As an athlete himself, Groot believes that everyone should know more about their bodies, and he has that coiled athletic spring in him, emblematic of that singular creature who always knows where every part of his body is at any given moment. It’s a characteristic that leads to the kind of “quiet intensity” he identifies in his mentor, and clearly, here at the end of his first semester in the anatomy lab, it is already working its magic to inspire others.

The model that Nielsen developed of empowering undergraduates as teaching assistants and mentors to scale up the volume of undergraduate anatomy students, is one that Groot hopes to maintain, and even expand if needed. Considering that the SBS has seen a thirty percent increase in student enrollment this year, growth is likely, and the funding will hopefully follow.

TAs in the Nielsen model typically have taught specific content at least three times by semester’s end. “You can’t just say ‘go teach,’” he explains, referring to the training of TAs who are all paid. “That what’s necessary to create skilled young teachers. And the students love it! There’s a feeling of camaraderie [among undergraduates]. They feel like they are a part of something.”

Kudos

Distinguished Professor Baldomero “Toto” Olivera and his team of researchers were awarded a Golden Goose Award in September. Impeded by supply chain issues while conducting DNA research in the Philippines, Lourdes Cruz and Olivera began examining cone snails, a group of highly venomous sea mollusks which happened to be in abundant supply along the country’s coastal waters. Several decades and countless airline miles later, and with the help of then-undergraduate students Michael McIntosh and the late Craig Clark, the team discovered the raw material for a non-opioid pain reliever and a powerful new tool for studying the central nervous system, all hidden in the cone snail’s potent venom.

Distinguished Professor and former Director of the SBS M. Denise Dearing is the new Division Director at the National Science Foundation (NSF) for Integrative Organismal Systems. The appointment was effective August 15. The division is one of four within the Directorate of Biological Sciences at the NSF and provides vision and leadership, and contributes to the agency’s mission by supporting fundamental research to advancing our understanding of organisms as integrated units of biological organization.

Thure Cerling, Distinguished Professor of Biology; Distinguished Professor of Geology and Geophysics; and Francis H. Brown Presidential Chair, was awarded the 2022 Rosenblatt Prize, the University’s highest honor given to faculty. Known for founding the stable isotope research lab SIRFER with SBS’s Jim Ehleringer, Cerling “has made important and impactful contributions to science using isotope geochemistry to learn about natural processes,” according to the citation by University president Taylor Randall. Cerling was, until recently, also chair of the Department of Geology & Geophysics at the U.

The School of Biological Sciences has appointed Ofer Rog, assistant professor of biology, as the Mario Capecchi Endowed Chair. The prestigious three-year faculty appointment will allow Rog to continue his work studying the synaptonemal complex (SC)—a conserved structure that underlies chromosomewide behaviors during sexual reproduction.

The U established the chair to honor Utah’s first Nobel laureate, Mario Capecchi, through a generous gift from the George S. & Dolores Dore Eccles Foundation.

A native of Israel, Rog earned his BS and MS from Tel Aviv University, followed by a PhD at Cancer Research UK, University College London and postdoctoral research at UC Berkeley before arriving at the U.

Fond Farewells

Norman Curtiss Negus

(1926–2022)

SBS Emeritus professor, Norm Negus’s lifelong love of animals and the outdoors led him into a very successful professional career of teaching and research at both Tulane University and the University of Utah. He took immense pleasure and pride in guiding students at both the undergraduate and graduate levels. His research with animals and the environment allowed him to be in the outdoors that was his passion. When he was not trapping animals or collecting plants he could be found with his dogs fly fishing, hiking and hunting in the Rocky Mountains that he loved. He passed away just two weeks before his 96th birthday.

Remembered as a remarkable man who had a wonderful life, he served his country in World War II in the Army Air Corp. After the war he completed his undergraduate and Master’s Degree in Zoology from Miami University in 1950, and a PhD in Biology from The Ohio State University in 1956. He taught biology at Tulane from 1950 to 1970. In that year he accepted a position as Professor of Biology at the University of Utah where he worked until his retirement in 1995.

A father of four children, he later married Patricia Jane (aka Pat Berger) in 1973, a biologist in her own right (and, currently, SBS faculty emerita). Together they pursued joint careers of teaching and research at the U.

You can read expanded remembrances at biology.utah.edu.

Robert Vickery

(1922–2022)

Emeritus Faculty Dr. Robert Kingston Vickery Jr passed away eight weeks before his 100th birthday. “Bob was an internationally recognized Plant Geneticist and Chair of the Department of Genetics, one of the traditional Departments at Utah that were merged to form the Biology Department,” says friend and colleague Baldomero “Toto” Olivera. “He was responsible for recruiting [the late] Gordon Lark to Utah as Chair of the new Biology Department; as a senior member of the merged Department, he played a key role in establishing the creative and collaborative interactions between the disparate disciplines of Biology.”

In a tribute during this year’s SBS Science Retreat, plant biologist and colleague of Vickery’s Lynn Bohs spoke fondly of her association and of Vickery’s signature garb of shorts and a cheery yellow shirt that he wore in the field and in the greenhouse atop South Biology building. A great lover of plants, Vickery attended first grade in a Montessori school in Rome, Italy where he skipped the reading lessons, preferring to learn how to grow plants in a planter box. He graduated from high school in Berkeley California and attended Stanford University before and he served in the Army Air Corps during WWII. While there he witnessed the famous raising of the Stars and Stripes over Mount Suribachi.

Presented with a Distinguished Teaching Award in 1972, Vickery’s research model was the monkey flower (mimulus). He also loved to teach. For many years he led trips of students and high school science teachers to the Galapagos Islands to learn in the environment that inspired Charles Darwin.

George R. Riser

(1923–2022)

In 2017 George R. Riser BS’47, received the Distinguished Alumni Award from the School of Biological Sciences. It was an auspicious award for a truly auspicious man in part because of Riser’s sustained funding of the Riser Endowed Scholarship Fund which has provided annual scholarships to thousands of graduate and undergraduate students in biology along with travel awards for field research.

Following his graduation from the University of Utah, Riser went on to New York City to study voice with Enzo Serrafini and at the Philadelphia Conservatory of Music. Later, returning to his science background, he became a physical chemist for the U.S. Department of Agriculture where he worked for 23 years. He passed away at age 98 in Huntingdon Valley, PA.

Ellen Louise Radike

(1954–2022)

A former SBS teaching lab coordinator, Ellen Radike passed away July 22. A graduate of Mount Notre Dame High School in Cincinnati, Ohio, she received her medical technology degree from the University of Cincinnati. In the 70s she worked in the Grand Teton National Park in the 1970’s and fell in love with the mountains.

She worked at several different labs and scientific companies but, in part because of her love mountains, settled in at the University of Utah where she ran the biology teaching labs. Remembered by many on campus as the woman with the black Great Dane Maia by her side, she was also, according to former Co-Director Leslie Sieburth, a caring mentor to biology undergraduates, many of whom went on to graduate school and careers in science. She is survived by her son Jesse, five siblings and many nieces and nephews.

SCIENCE RETREAT & LARK LECTURE

Remembrances of recently-deceased faculty members were given at the Science Retreat & Lark Lecture on October 6th. The new graduate student cohort was welcomed with a variety of research

presentations from faculty, post-docs and graduates. The Lecture was presented by Ron Davis (Stanford University), followed by a reception and display of research posters by both undergraduate and graduate students.

This is the first year for the Lecture since its namesake, K. Gordon Lark, passed away in 2020. SBS’s current campaign to fully endow the Lark Endowed Professorship continues with a $1:$1 match. (Details on back cover)

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Lark Endowed Professorship

Biological Sciences

line back to Gordon Lark (1930- 2020, the “father” of the Department of Biology (now SBS). An endowed professorship in his name is how U Biology has chosen to secure his legacy of research, teaching and innovative, even daring-in-its-day, leadership.

We have secured a $250,000 match so that your gift to fully fund an endowed professorship in Dr. Lark’s name will be matched dollar-for-dollar.

Undergraduate Scholarship Incentive

The University of Utah has encouraged colleges and departments to offer additional undergraduate scholarships to continue to alleviate the financial burden on our students. Donor funded scholarships allow the School of Biological Sciences to provide life-changing educational and research experiences at an exceptional value.

Building Visual Hypotheses. The Animation Lab at the U creates information-rich and visually compelling animations that capture current hypotheses on diverse molecular and cellular processes. These visualizations have broad applications in scientific research, communication, education and outreach, including in SBS’s The Rog Lag interested in better visualizing condensates. Photo credit: animationlab.utah.edu

Thanks to all of our alumni and friends who have already made a donation to this worthy cause. And thank you in advance to those who may be in a position to help us reach our matching goal here at the end of the year.

Please consider helping our students through a scholarship contribution today. For a limited time, the University is also offering some matching incentives for new multi-year scholarship pledges and/or new endowed scholarships. Considering naming a permanent scholarship to support biology students? Now is the perfect time to do so.

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