bio-news

Darwin’s Pigeon “Enigma”

September 22, 2021

Darwin’s short-beak enigma

Charles Darwin was obsessed with domestic pigeons. He thought they held the secrets of selection in their beaks. Free from the bonds of natural selection, the 350-plus breeds of domestic pigeons have beaks of all shapes and sizes within a single species (Columba livia). The most striking are beaks so short that they sometimes prevent parents from feeding their own young. Centuries of interbreeding taught early pigeon fanciers that beak length was likely regulated by just a few heritable factors. Yet modern geneticists have failed to solve Darwin’s mystery by pinpointing the molecular machinery controlling short beaks—until now.

In a new study, biologists from the University of Utah discovered that a mutation in the ROR2 gene is linked to beak size reduction in numerous breeds of domestic pigeons. Surprisingly, mutations in ROR2 also underlie a human disorder called Robinow syndrome.

“Some of the most striking characteristics of Robinow syndrome are the facial features, which include a broad, prominent forehead and a short, wide nose and mouth, and are reminiscent of the short-beak phenotype in pigeons,” said Elena Boer, lead author of the paper who completed the research as a postdoctoral fellow at the U and is now a clinical variant scientist at ARUP Laboratories. “It makes sense from a developmental standpoint, because we know that the ROR2 signaling pathway plays an important role in vertebrate craniofacial development.”

The paper published in the journal Current Biology on Sept. 21, 2021.

Mapping genes and skulls

Two domestic pigeon breeds photos facing each other, the left one has a very short beak, big black eye, white feathers on the head with a crest sticking up. The right pigeon has gray brown feathers on the head with a red eye ball, and a beak that's about twice as long as the other birds.

PHOTO CREDIT: Sydney Stringham

Old German Owl (left) and Racing Homer (right) domestic pigeon breeds.

The researchers bred two pigeons with short and medium beaks—the medium-beaked male was a Racing Homer, a bird bred for speed with a beak length similar to the ancestral rock pigeon. The small-beaked female was an Old German Owl, a fancy pigeon breed that has a little, squat beak.

“Breeders selected this beak purely for aesthetics to the point that it’s detrimental—it would never appear in nature. So, domestic pigeons are a huge advantage for finding genes responsible for size differences,” said Michael Shapiro, the James E. Talmage Presidential Endowed Chair in Biology at the U and senior author of the paper. “One of Darwin’s big arguments was that natural selection and artificial selection are variations of the same process. Pigeon beak sizes were instrumental in figuring out how that works.”

The short- and medium-beaked parents produced an initial F1 brood of children with intermediate-length beaks. When the biologists mated the F1 birds to one another, the resulting F2 grandchildren had beaks ranging from big to little, and all sizes in between. To quantify the variation, Boer measured beak size and shape in the 145 F2 individuals using micro-CT scans generated at the University of Utah Preclinical Imaging Core Facility. 

“The cool thing about this method is that it allows us to look at size and shape of the entire skull, and it turns out that it’s not just beak length that differs—the braincase changes shape at the same time,” Boer said. “These analyses demonstrated that beak variation within the F2 population was due to actual differences in beak length and not variation in overall skull or body size.”

An animation of the skulls of birds showing the variety of beak lengths from short to long.

PHOTO CREDIT: Elena Boer

High-resolution scans of the grandchildren of the Racing Homer and German Owl cross. The animation shows the variety of beak lengths from shortest to longest.

Next, the researchers compared the pigeons’ genomes. First, using a technique called quantitative trait loci (QTL) mapping, they identified DNA sequence variants scattered throughout the genome, and then looked to see if those mutations appeared in the F2 grandkids’ chromosomes.

“The grandkids with small beaks had the same piece of chromosome as their grandparent with the small beak, which told us that piece of chromosome has something to do with small beaks,” said Shapiro. “And it was on the sex chromosome, which classical genetic experiments had suggested, so we got excited.”

The team then compared the entire genome sequences of many different pigeon breeds; 56 pigeons from 31 short-beaked breeds and 121 pigeons from 58 medium- or long-beaked breeds. The analysis showed that all individuals with small beaks had the same DNA sequence in an area of the genome that contains the ROR2 gene.

“The fact that we got the same strong signal from two independent approaches was really exciting and provided an additional level of evidence that the ROR2 locus is involved,” said Boer.

The authors speculate that the short-beak mutation causes the ROR2 protein to fold in a new way, but the team plans to do functional experiments to figure out how the mutation impacts craniofacial development.

Headshots of domestic pigeon breeds. The left four have short beaks, the right four have medium or long beaks.

PHOTO CREDIT: Thomas Hellmann, adapted from Boer et al. (2021) Current Biology

Representative images of individuals representing short beak (left four birds) and medium or long beak (right four birds) pigeon breeds (image credit: Thomas Hellmann). Short beak pigeons, from left to right: English Short Face Tumbler, African Owl, Oriental Frill, Budapest Tumbler. (B) Medium/long beak pigeons, from left to right: West of England, Cauchois, Scandaroon, Show King. The short-beak birds all had the same ROR2 mutation.

Pigeon enthusiasts

The lure of the domestic pigeon that mesmerized Darwin is still captivating the curious to this day. Many of the blood samples that the research team used for genome sequencing were donated from members of the Utah Pigeon Club and National Pigeon Association, groups of pigeon enthusiasts who continue to breed pigeons and participate in competitions to show off the striking variation among breeds.

“Every paper our lab has published in the last 10 years has relied on their samples in some way,” said Shapiro. “We couldn’t have done this without the pigeon breeding community."

 

by Lisa Potter - originally published in @theU

Be the Light

August 16, 2021

Be the light in your community

On July 14-16, 2021, students of the American Indian Services (AIS) Pre-Freshman Engineering Program (AIS PREP) came to the University of Utah to celebrate the completion of their 2021 AIS PREP, co-hosted by the College of Science. AIS PREP is a free program for Native American students to take advanced science, technology, engineering and mathematics (STEM) courses for six weeks for three consecutive summers. At the end of the program, the students earn scholarships to any higher education institution that they choose and continue to receive financial assistance. The 2021 AIS PREP group included 113 students from different Native American tribes: Navajo (Diné), Hopi, Oglala Sioux (Lakota), Shoshone/Bannock, Zuni, Crow, Paiute, and Cheyenne. AIS PREP is focused on making the curriculum culturally sensitive to the Native American students they serve. They bring a unique opportunity to keep the students close to their homes.

“We’re the only non-profit that has taken on such a big program like this. Some of these tribal communities are in rural areas—resources are scarce,” said Meredith Little Lam, project and program manager at AIS and AIS scholarship alumnus. “The whole point of AIS PREP is that we want to make sure we give our Native American students STEM resources that will allow them to succeed in high school.”

The students traveled to the U on July 14 to stay in campus dorms, meet PREP students from other AIS PREP sites, and hear presentations from U staff and College of Science faculty to celebrate the completion of the program. The week ended with a keynote address from the architect, inventor and entrepreneur Alice Min Soo Chun, during which she shared her inspiring story of changing the world by inventing a durable, portable, collapsible solar light.

“These students come from some of the poorest reservations in the United States. This really is a trip of a lifetime for them,” said Little Lam, “Some come from areas where there’s no running water, no electricity. We live in the United States and it’s just appalling that we can’t figure out ways to help these communities. And so, I think that this is a proactive way of getting these students involved in STEM to let them know, ‘You can change your tribal communities. You have it within yourself to be that leader.’”

“The College of Science is honored to have taken part in celebrating this incredible accomplishment of completing AIS PREP,” said Cassie Slattery, director of special projects of the college. “We would be lucky to have any one of these exceptional students pursue science here at the U.”

Anyone can be a scientist


On Thursday, the students learned about a diverse array of topics from speakers, including Donna Eldridge (Navajo/Diné), program manager of Tribal outreach for Health Equity, Diversity, & Inclusion, Amy Sibul of the School of Biological Sciences, Paul Ricketts of the South Physics Observatory, Julie Callahan (Little Shell Tribe of Chippewa) of ASPIRE, and Kyle Ethelbah (Western Apache), director of the U’s TRIO programs. One of the day’s highlights was an explosive presentation from chemist Ryan Stolley. He threw balls of fire, inhaled sulfur hexafluoride to give himself a funny low voice, and had the students freeze flowers with liquid nitrogen and smash them to bits. In between the chemistry magic, Stolley shared his personal story.

“I was a Native American student, of the Choctaw Nation of Oklahoma. When I was young, school was not my focus—I was just getting into trouble. But I got a lucky break and met some chemists who really changed my life,” said Stolley. “Native students are severely underrepresented in STEM disciplines. I love any opportunity to show them that it’s possible to pursue science. I mean, I’m covered in tattoos. Anybody can be a scientist. You just have to be curious.”

Stolley spoke to the students about attending Fort Lewis College, a university in Colorado that offers free tuition to Native American students. He received a doctoral degree in organic chemistry from the U and was a postdoctoral research assistant at the Pacific Northwest National Laboratory. He returned to Salt Lake City as a research assistant professor first in the Department of Chemistry and now in the College of Science, as well as part owner of a local chemical company.

“Part of what my company does is to make products that help clean contaminants out of water across the Colorado Plateau, especially on Tribal lands,” Stolley said, “I want to get these students thinking about how we can take our science and turn it around to help our Native communities.”

Creating positive memories on campus is part of how AIS PREP helps plant the seed to pursue higher education.

“We’re excited to be partnering with the U and having the ability to connect these students with faculty and current student volunteers who are Native American so that they can instill in their minds that it’s not an impossible dream,” said Little Lam. “Maybe they’ll be teachers and maybe they’ll be researchers, but wherever they may be, they can contribute to their Tribal communities. AIS doesn’t just stop with them after they graduate. We give them financial resources, but also say, ‘Hey, we’re here for you. Even after you finish this program.’”

A problem is an opportunity in disguise

This is the first year that AIS invited a keynote speaker to address the students during their program completion celebration. For Little Lam, Alice Min Soo Chun was the perfect choice. Chun, founder and CEO of Solight Designs, Inc. invented the Solar Puff, a portable, collapsible, self-inflating light powered by the sun. Little Lam met Chun while at Navajo Strong, through which Chun donated Solar Puff lights to families on the Navajo Nation without access to electricity.

“Every problem is an opportunity in disguise,” Chun, who is also a professor at Columbia University, told the AIS PREP graduates. “By doing research and observing, anybody can do this.”

Chun’s passion for solar energy began when her son was diagnosed with asthma, a condition that was aggravated by New York City’s poor air quality. Chun was inspired to find energy solutions that would reduce air pollution and its impacts on respiratory health. She realized that her son’s respiratory issues were global; without access to electricity, millions of people are forced to burn kerosene lanterns for lighting that produce noxious fumes. She saw a need for solar lights that were durable and collapsible, but the only ones available had to be inflated, leaving users vulnerable to bacterial infections. So, she invented a foldable design that drew from her childhood.

“I’m Korean. When I was a little girl, my mother taught me origami when I was young. Origami is an incredibly powerful tool,” she said. “Paper on its own can’t stand up. Fold it once, you have a corner, you have structure.”

Through the “Give a Light” program, Solight Designs has supplied Solar Puffs to Haiti, Puerto Rico, The Florida Keys, Ghana, Ecuador, Miami and more after natural disasters left people without power. During her keynote address, Chun passed out Solar Puff lights to everyone in attendance and turned off the lights. Everyone switched on their solar lanterns, eliciting ooo’s and aww’s. The lights illuminated the entire auditorium, demonstrating the invention’s power.

“I used to get beat up a lot for looking different. So, I became a fighter—not with my fists, but with the light of my heart and mind. You are all light warriors,” Chun said. “My hope is that you leave understanding how powerful you are and that you have the ability to change the world.”

by Lisa Potter - originally published in @theU

Birds of the Philippines

June 16, 2021

What factors put Philippine birds at risk of extinction?

The lush forests and more than 7,000 islands of the Philippines hold a rich diversity of life, with 258 bird species who live nowhere but the Philippine archipelago. A new study from University of Utah researchers suggests that, due to deforestation and habitat degradation, more bird species may be endangered than previously thought—including species that may not have been discovered yet. The study is published in Frontiers in Ecology and Evolution.

“Our study provides a roadmap for not only which species may warrant heightened conservation attention,” says Kyle Kittelberger, a doctoral student in the University of Utah School of Biological Sciences. “But which traits a species may have that can help inform if it may likely be more at risk of extinction.”

Birds of the Philippines

Phillippine Frogmouth

Located in Southeast Asia, the Philippines is considered a global biodiversity hotspot and one of the most biodiverse countries in the world, hosting nearly 600 bird species. A high proportion of the wildlife is endemic to the country, meaning that it is found nowhere else. The Philippines also hosts some of the highest richness of species recently identified as distinct from other closely related species, showing that scientists still have much to learn about the Philippine ecosystems.

Within the last decade the number of endemic species has risen from 172 to 258. This increase of 86 endemic species is more than all the endemic bird species in China (67) or India (75) and more than any country in South America or Africa.

Çağan Şekercioğlu, an associate professor in the School of Biological Sciences who has done ornithological field work in over 90 countries on all continents cannot forget his first visit to the islands.

“When I first visited the Philippines in 2008, I was awestruck by the diversity and especially the endemism of its avifauna but also greatly depressed by the rapid loss of habitat,” he says. Excursions into the field took hours due to extensive deforestation. “While looking for rare forest birds in the lowlands of Mindanao, we were literally trying to keep ahead of the loggers that were cutting down century-old rainforest trees within a couple hundred meters of us,” he adds. Despite that, in 13 days he saw 161 bird species he had never seen before—and still has 163 bird species to go.

Deforestation, habitat degradation and wildlife exploitation, however, threaten that biodiversity. Southeast Asia, the authors write, is forecast to lose over a third of its biodiversity over the next century. The Philippines in particular ranks eighth in the world for the number of globally threatened bird species.

“There is a pressing need to assess what traits make some species more at risk of extinction than others and to use this understanding to help inform conservation efforts,” Kittelberger says.

Traits of threatened birds

To understand the status of Philippine birds, the researchers first determined the bird traits most predictive of extinction risk by correlating bird species’ ecological and life-history traits, including body mass, diet, elevation range, and clutch size (the number of eggs laid in a nesting season) with their conservation status. A species endemic to the Philippines was significantly more likely to face an extinction risk, they found. Narrow elevation ranges, dependence on forests and high body mass also put birds at risk for extinction.

Philippine Serpent-eagle

Then the researchers turned around and evaluated Philippine birds’ expected conservation status using those traits, comparing predicted conservation status with the IUCN Red List conservation designations. They found that 84 species were predicted to be in worse shape than their Red List designation, with 14 species predicted to be globally threatened (i.e. vulnerable, endangered, or critically endangered) that aren’t currently classified as such.

“We predicted that the Philippine Serpent-eagle and Writhed Hornbill, two species that are not currently recognized as being globally threatened, are respectively endangered and critically endangered,” Kittelberger says. “We also predicted that the Palawan Peacock-pheasant, Calayan Rail and Philippine Eagle-owl, three species currently recognized internationally as being vulnerable, are likely endangered species. All these birds, therefore, warrant heightened conservation attention as they may be more threatened than currently believed.”

Lost before they’re found

Among the 84 species predicted to be more threatened, 12 were recently recognized as separate species, and three of those were predicted to be “vulnerable.”

Palawan Peacock-pheasant

“The Philippines have a very high level of endemism and it is currently estimated that there are twice as many bird species in the Philippines that have not yet been split and officially recognized, so there is a real risk of losing species before they are described,” Kittelberger says.

Kittelberger says that their research can be applied broadly to assess the conservation status of birds throughout the region.

“The most important thing that the Philippines can do to protect birds,” Kittelberger says, “is to address the high levels of deforestation, habitat degradation, and wildlife exploitation, and to increase land protection for wildlife and increase funding for conservation efforts.”

Find the full study at https://www.frontiersin.org/articles/10.3389/fevo.2021.664764/full 

Co-authors also include Montague H. C. Neate-Clegg, J. David Blount and Çağan Şekercioğlu of the U’s School of Biological Sciences, Mary Rose C. Posa of the California Botanic Garden and John McLaughlin of the University of California, Santa Barbara. The study was supported by the Christensen Fund.

 

By Paul Gabrielsen, first published in @theU

Todd B. Alder

June 9, 2021

Todd Alder

Todd B. Alder contracted COVID-19 early on in the pandemic and today still suffers from residual effects. But being just a “long hauler” as opposed to the alternative is what he calls being “lucky.” Says Alder, “Like many of us (I am guessing), this virus has disrupted my life with family and friends, my law practice, and my ability to travel. But on the plus side, I am really enjoying the Zoom calls where I am wearing a dress shirt and tie on top and something very questionable on the bottom.”

It's a scenario of late that many of us find ourselves experiencing (working on Zoom, not necessarily being pant-less), but the light touch that this biologist-turned-patent-attorney has towards not only the pandemic but work and life itself is evident. And so is his generosity. In April Alder was a featured alum in the School of Biological Sciences’ BioLuminaries speaker series (on Zoom, of course). As a registered patent attorney and partner at Thorpe North and Western (TNW) in Sandy, Alder illuminated the circuitous path one can take as a biology student toward fulfillment and job security… not to mention the love of chihuahuas.

More on that later.

The Road Less Traveled

Alder points to his PhD advisor, SBS’s Gary Rose, as the mentor who gave him “great direction over the years, particularly when I was stuck.” At the time Rose’s lab primarily focused on the neurophysiology of electrosensory systems in electric fish. Alder took an alternate path to study neuronal mechanisms underlying temporal processing in the auditory midbrain, a subject related to Rose’s PhD dissertation from a decade earlier. It was Rose’s broad way of thinking about science, research and the labyrinth that is life and career that still benefits Alder today.

“My dissertation was very broad over some fairly diverse scientific disciplines. This would not have been possible without Gary's early influence in teaching that young graduate student to not only see the world in a different way, but to approach problems and question them in a different way as well. I will always be grateful to Gary for helping me to see that there are no isolated questions or problems in science, but that everything has a much broader context and, as Robert Frost wrote, ‘that has made all the difference.’"

That difference played out while Alder was at the U in a remarkably refreshing and surprising way. “I was recording from a neuron in the midbrain of an anuran amphibian,” he explains, “and I thought of a test to further understand how these particular neurons worked.” Normally, neurons are not held in a stable state long enough for the kind of procedure Alder was planning. “But I stopped the program that was making the frog calls and quickly wrote a section of code so the program could do the test.”

It was that recompiling of the code—and a few crossed fingers—that led to a startling discovery. Once he turned the equipment back on the neuron in question was still there. From that test Alder showed that the generally accepted theory explaining how a neuron differentiates between high and low pulse rates was wrong. It turns out that neurons do not accomplish this differentiation though energy integration. Instead, Alder found that neurons were actually counting the number of pulses that occur within the range of pulse rates to which the neuron is tuned.

“That was one of the most exciting days of my life,” Alder says, “and I have always been amazed that those very complex questions were answered with [a] test performed on one neuron (it was repeated of course).” Alder graduated from SBS with his PhD in 2000.

Tripping the Patent Fantastic

Over the course of seven years, the mixture of biology, neurophysiology, molecular biology, etc. actually led to a degree in law which in turn opened up many opportunities for Alder to work with some very diverse and fascinating technologies. Enter his work in patent law following a clerkship at TNW beginning in 2002.

A Utah native, Alder hasn’t moved far geographically (he still lives in Utah and received all three of his degrees, including his law degree, from the U). But career-wise and developmentally it has been a galactic trip. For this reason he is quick to remind up-and-coming biologists at the U that education is not, and should never have been, about getting a job. “If you really contemplate the principles you are learning and integrate them into your life, it will change you and the way you think. To me, that is worth so much more than what type of job your degree can get you.”

About dogs … and a bear

Perhaps because of his wide-ranging academic, research and now patent career, Alder’s interests, like his dissertation, are broad and diverse. He loves to rock hound, watch horror movies, study theoretical physics and philosophy, collect old books, and “seriously mess with door-to-door sales people.” (Hopefully, while masked.) “Oh, and I once goosed a black bear in the wild, which made him terribly grumpy. But that is a story for a different day... .”

Which brings us to another enduring interest of Todd Alder’s and that is his love of chihuahuas. One advantage of working from home non-stop, quarantined from everyone else, is that your pets become a fixture, a pain and, if cuddly enough, a kind of accessory for that dress shirt above that questionable garment immediately below.

You can watch a recording of the BioLuminaries lecture by Todd Alder and co-presenter Heng Xie (PhD’04) on SBS’s YouTube Channel here.

 

By David Pace

Are you a Science Alumni? Connect with us today!

Nikhil Bhayani

June 2, 2021

Nikhil Bhayani

“Every time I come to the U with my kids,” says Nikhil K. Bhayani, MD, FIDSA (BS’98), “I take them on a reality tour. I [recently] told my youngest son, ‘Let’s retrace my footsteps when I used to go from one of the lecture halls at Presidents Circle, to the Student Union. This is the way my day was like.’”

They ended up at the Pie Pizzeria Underground, a decades-long favorite haunt of students and faculty just west of main campus on 2nd South, famous as much for its densely graffitied walls as its provocatively named specialties like “Hawaii Pie-O” and “Holy Shittake.” “It really feels like a college campus,” says Bhayani of the U. “My son tells me that he wants to get pizza here [at the Pie] every day.”

Though born in Virginia, Bhayani considers Salt Lake City, where he was raised, home. His parents, both originally from India, married in New York City after Bhayani’s father had finished graduate studies at the University of Rhode Island.

“I always wanted to go to medical school,” says Bhayani who graduated in 1998 with a biology major and a chemistry minor. (His brother Mihir also graduated from the University of Utah with a degree in chemistry in 2000 and is also a medical doctor.) While an undergraduate he worked in a bioengineering lab run by Richard Normann, and later in one of the labs at the Moran Eye Center. He recalls fondly some of his fellow Indians, in particular Rajesh, Monica and Leena Gandhi, a few years older than he, but also graduates in biology who went onto medical careers in infectious diseases and cancer.

Bhayani later attended Ross University School of Medicine in Portsmouth, Dominica, and was awarded his medical degree in 2003. In 2006 he completed medical residency training at Mercy Hospital and Medical Center in Chicago where his brother currently lives.

Nikhil and his family now live in Texas where he practices medicine at Dallas-Fort Worth Infectious Diseases, an integrated health care network comprised of physicians, hospitals, case managers, community clinics, and managed care partners.

There he also enlisted as an Infectious Diseases and Epidemiology Physician Advisor at Texas Health Resources in Arlington. In 2016, Bhayani was named Physician of the Year by the Texas Health Arlington Memorial Hospital. Not one to rest on his laurels, he was hired earlier this year as an Assistant Professor in the Department of Internal Medicine, at Texas Christian University and the University of North Texas School of Medicine where he brings his undergrad U experience full-circle by teaching pre-med-students. Especially gratifying recently was when a graduating senior, also interested in infectious diseases, came to him to ask if he could “shadow” him for four weeks for one of the student’s electives.

In clinical practice, says Bhayani, who works long-term with patients who live with HIV and other infectious diseases, “the research is always changing what we do. You have to keep up with developing trends… . We get patients who are insured, who have steady jobs and who are a little more educated, so when they read about new medications they want to make sure they're getting the latest. In private practice you want to be at the top of your educated game. This motivates me to stay on top too."

In his administrative role as physician advisor, Bhayani oversees all infectious disease policy-making—like the use of antibiotics, what lab teams are going to be doing—at fifteen acute care hospitals under the umbrella of the Texas Health Resources system. With a large African immigrant population Dallas/Ft. Worth, also home to a major international airport, experiences emerging infectious diseases and thus needs intense anti-microbial stewardship, including CDC protocols and cooperation with the local health department. Bhayani is at the center of these various sector components.

As you grow up and become successful, always look back and reflect how you got there and give back to the community you were nurtured in.”

It’s an intense but meaningful career, and sometimes Bhayani considers what it would be like to return more to teaching and mentoring, the kind that he feels he got at the University of Utah’s School of Biological Sciences. “My dad always said, ‘As you grow up and become successful, always look back and reflect how you got there and give back to the community you were nurtured in,” says Bhayani. Even so, he never wants entirely to give up his clinical experience at what amounts to the largest nonprofit based healthcare group in the country, second only to Intermountain Healthcare based in Salt Lake City.

“As I reflect, who I am today is thanks to my parents and the University of Utah for giving me motivation and an opportunity to pursue higher education,” says Bhayani who with his wife of eighteen years, also originally from India where her parents still live, is busy raising two sons. This while trying to keep up with following the NBA, NFL and, of course, the Utes, which he loves.

“Most of the work is done by my wife,” Bhayani concedes. He refers to her as the “pillar of the house, that “she keeps everything going. Left to me it would be like college all over again.”

Pizza anyone?

In May 2021, after months of battling the COVID-19 pandemic, Bhayani was selected as Top Physician of the Year by the International Association of Top Professionals (IAOTP) for his outstanding leadership and commitment to the healthcare industry.

 

by David Pace

Are you a Science Alumni? Connect with us today!

Diana Montgomery

May 17, 2021

Diana Montgomery

“Perhaps my favorite experience at the University of Utah is when I started working in a biology lab for the first time and realizing I fit in and enjoyed the work and the people there,” says Diana Montgomery, BS’87 in Biology. “It certainly helped to solidify my career choice.”

While at the U, Diana worked in Allen Edmundson’s crystallography lab on Wakara Way. In addition to learning practical skills, Diana was included in the research publication, titled “A mild method for the preparation of disulfide-linked hybrids of immunoglobulin light chains” in 1987. The journal was Molecular Immunology. (Read the paper here.)

Shortly thereafter, Diana graduated from the U and moved to Baltimore, Maryland, to begin graduate school at Johns Hopkins University. Her advisor was Ernesto Freire, a well-known expert in biological thermodynamics. Diana completed a doctorate degree in Biology/Biophysics from Johns Hopkins in 1994 and conducted postdoctoral work at Northwestern University in the lab of Richard Morimoto and at the University of Massachusetts in the lab of Lila Gierasch.

Diana is now a Principal Scientist in the department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism at Merck, in Pennsylvania. She focuses on developing therapeutic proteins as new drugs, two of which are now FDA-approved products, tildrakizumab and bezlotoxumab.

Tildrakizumab (brand name Ilumya) is approved for the treatment of adult patients with moderate-to-severe plaque psoriasis in the United States and Europe. Tildrakizumab is a monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses.

Bezlotoxumab (brand name Zinplava) is a monoclonal antibody designed for the prevention of recurrence of Clostridium difficile infections, which can be life-threatening. Bezlotoxumab works by binding to a specific toxin produced by the Clostridium difficile bacteria and neutralizes the toxin’s effects.

Merck is a multinational company and one of the largest pharmaceutical companies in the world, employing some 74,000 people. In 2020 alone, Merck invested $13.6 billion in drug research and development.

Diana has 24 research publications with nearly 1,400 citations to her credit. Her recent work has focused on describing the effects of immunogenicity on therapeutic proteins. One liability of protein-based therapeutics is their tendency to elicit an unwanted immune response against themselves. One of the manifestations of such an immune response is the activation of B cells, which produce anti-drug antibodies that bind to therapeutic protein drugs and can reduce a drug’s therapeutic effects or be associated with safety issues. Therefore, an important part of therapeutic protein drug development is to characterize the tendency of a drug to elicit anti-drug antibodies and any potential effects on clinical pharmacokinetics, efficacy, and safety.

Reflecting back to her childhood, Diana recalls several key moments that motivated her to study science.

“My father was a mining engineer. He did some geology education while we were hiking, like what type of rocks were on the trail and how to recognize fool’s gold,” says Diana. “When we went camping, he’d explain the Pythagorean theorem with the triangles of the tent. It made math and science familiar to me.”

In high school, Diana developed an interest in molecular biology and biochemistry. She then chose to attend the University of Utah because it was a reputable research university which was close to home. (Diana grew up in Tooele, Utah, about 30 miles from the U.) Diana received an Honors at Entrance scholarship to begin her studies at the U, based on her achievements in high school.

“At the U, several classes in the Department of Biology (now School of Biological Sciences) were designed to encourage students to make and test hypotheses. This form of experimental-based learning was both effective and highly enjoyable,” said Diana.

“Professors like Gordon Lark and John Roth were fantastic. They made their lectures interesting and taught us how to think like a scientist and how to do science in the laboratory. I was lucky to be a part of that, but at the time didn’t realize it was so rare. I believe it is important for students to get a feel for doing science in introductory classes like these, rather than being exposed to it for the first time in graduate school. By the end of my undergraduate years, I was hooked on the scientific paradigm of hypothesis, design, experiment, and interpret. I have the U to thank for that.”

Diana and her husband, Hwa-ping (Ed) Feng have two children, Ellen and Nathan. Diana particularly enjoys gardening and reading. She also volunteers at a local food pantry and at animal-adoption clinics.

The College of Science and its four academic departments – Biological Sciences, Chemistry, Mathematics, Physics & Astronomy – now graduate more than 650 students each year. We are proud of our many alumni who live and work all around the world. Please share your stories with us!

Are you a Science Alumni? Connect with us today!

Sahar Kanishka

April 30, 2021

Undergraduate Research Award

Sahar Kanishka

Biology major receives 2021 Outstanding Undergraduate Researcher Award.

Sahar Kanishka remembers daily where her family came from, where they are now, and what opportunity there is for her at the School of Biological Sciences (SBS).

“I’ve always wanted to be a doctor ever since I was younger,” she recently explained in a video interview. “Because my family’s from Afghanistan and they actually fled from the Soviet invasion, they were telling me how the medical resources over there were very scarce when they were escaping. Like things we take for granted here [in the United States]. I want to be able to give back in some way. And that’s my way of giving back, becoming a doctor and contributing what I’ve learned here.”

What Kanishka, now in her junior year as an honors student, is learning happens largely in the Gagnon lab at the SBS where she and her colleagues are studying vertebrate lineage and cell fate choice along with cell signaling and genome engineering. Their subject model is the living zebrafish with which they are attempting to answer the question of how biology builds an animal with millions of cells. The question is complicated by the fact that those millions of cells are continually sharing information while shape-shifting at the same time.

Zebrafish

A living organism is the culmination of science turning chaos and cacophony into a kind of marvelous symphony. Using CRISPR-Cas9 gene-editing technology, the Gagnon lab is busy marking cells with a genetic barcode that could later be used to trace the lineage of cells that in the zebrafish are similar to other vertebrates, including humans.

The micro “scissors” of CRISPR is no longer just being used to decode the genome, but to make a version, readable to humans, of what cells are doing in real time and how. It’s research that’s contributing to a sea change in genomic studies, and Kanishka is there at the bench experiencing it firsthand. The way Jamie Gagnon, Principal Investigator who holds the Mario Cappechi Endowed Chair at SBS, puts it, the research Kanishka is doing “may lead to a holy grail method for developmental biology—the ability to record developmental history, in living animals, with molecular and spatial resolution.”

Little wonder then that the Undergraduate Research Program at the University of Utah chose Kanishka for this year’s award. In his nomination letter Gagnon, who referred to Kanishka as having “transitioned quickly into an independent scientist," also wrote that he has been “impressed with Sahar’s poise, focus and commitment to research over the last year, which has been particularly challenging for our undergraduate researchers… . Sahar is already the face of STEM research in the College.”

Kanishka’s journey at the U threaded through ACCESS, a signature program of the College of Science. It was a scholarship and mentorship experience that led to re-figuring what research could be. Instead of working primarily on a computer in isolation and doing anatomy lessons from a book, ACCESS and SBS provided her with a hands-on approach in its full cadaver lab. As a pre-med student hoping to earn a joint medical degree and doctorate, Kanishka’s turn as a teaching assistant to professor Mark Nielsen gave her added invaluable experience. ACCESS also gave her a practical skill set, like creating her first research poster and then presenting it publicly.

The ACCESS program

The same has been true in the Gagnon lab where she says you are free to mold your research experience to your own expectations. Research at the U “fosters an environment of curiosity of real research. It’s really beautiful,” she says, “to have someone [like Gagnon] believe in you like that.” This, she concedes, in spite of feeling at times like an imposter as the child of an immigrant family and as a woman. She’s had to “learn through lots of struggles.”

Some lessons from those struggles have been hard won. “You can’t just put science in a box and tell it what to do,” she explains. “I have to allow it the freedom to seek to understand the world rather than to just understand me.” Her joint undergraduate degree in business administration speaks to Kanishka’s sense of the intersectionality of all learning. She was especially impressed with a recent visit by Reshma Shetty, the inaugural SBS Distinguished Lab Alumni who worked with Baldomera “Toto” Olivera in his lab and is a co-founder of Boston-based Gingko Bioworks, a bio-engineering start-up.

But the ballast in Kanishka’s life--both that of her academic career’s and that of her personal story’s--continues to be family. That includes not only her younger sister and parents here in Utah, but also her extended family in Afghanistan and beyond. “I hate that we’re separated by distance,” she says, referring to her overseas cousins, aunts and uncles as “my other parents and siblings. I owe everything to them. They mean everything to me.”

Until she and her extended family are all at least on the same side of the globe, Kanishka has both advice and a caution for her undergraduate colleagues. “Figure out if you want to do something by actually doing it,” she advises, recommending internships for high schoolers not bound for college, including through a program she helps facilitate as a volunteer called Talent Ready Utah. “College can be a business,” she warns, “pumping out students” for a job market they may not resonate with or even prosper in.

But Sahar Kanishka is optimistic about things as well. When asked about the pandemic and the social and economic upheaval, she proffers a winning smile, while adding, “I’m excited to see how college will change and adapt.”

 
by David Pace
 

Beckman Abstract

  • Lineage tracing in zebrafish with CRISPR prime editing (S. Kanishka)
    All embryos develop from a single cell. We use lineage tracing to map the relationships between individual cells and back to the initial founding cell. These lineage trees can help us understand how cells acquire their fates during normal development, and how that can go wrong in human disease. An emerging method for lineage tracing in embryos uses cellular barcodes. Cellular barcodes individually tag cells with a unique set of mutations specific to that cell. As cell divisions occur, the barcode is passed on to the progeny cells and a lineage tree can constructed based on cells that share similar barcodes. The CRISPR-Cas9 system for gene editing is an ideal tool for creating a huge diversity of cellular barcodes in embryos. However there are limitations with CRISPR-Cas9, including unpredictable indel formation and difficulties in recovering barcodes from cells. In this project, a modified CRISPR system known as prime editing will be applied in zebrafish, and utilized for lineage tracing. Prime editing allows for precise genome editing by inserting user-specified genetic sequences at a target site in the genome. I hypothesize that we can use prime editing to insert a huge library of user-specified barcodes into the genome of developing zebrafish. Because these barcodes are defined by the experimenter, they can be recovered at the end of the experiment using RNA in situ hybridization. In principle, lineage tracing with prime editing will allow us to discover the spatial arrangement of related cells in intact embryos and tissues. We hope to use lineage tracing with prime editing to understand the mechanisms of heart regeneration in zebrafish.

T. Mitchell Aide

April 28, 2021

T. Mitchell Aide

Distinguished Alumnus, Biology

Following his graduation with a bachelor’s from University of Texas - San Antonio, California native T. Mitchell (Mitch) Aide ended up in Utah … but via Panama. It was in Central America where he first met School of Biological Sciences (SBS) professors Lissy Coley and Tom Kursar doing tropical forest research. Aide would eventually become Coley’s first graduate student at the University of Utah. Lissy and Tom were “different than some other advisors,” says Aide. “They showed how high-quality research did not have to exclude enjoying life.”

The relationship proved to be a productive one. Aide graduated from U with a PhD in 1989 and continued in his career as a researcher and professor. Recently he was presented the School of Biological Sciences 2021 Distinguished Alumni Award.

During his sojourn at the U (1982-1990) Aide says that the cohort of professors there “created an environment of high-quality research and education

Stand-up guy on Stand up paddleboard (SUP)

without being aggressively competitive.” He remembers the personal and financial support of the department staff when a house he lived in with other graduate students burned down. His graduate work included a single-authored publication in Nature in 1988, demonstrating that the synchrony of production of young leaves for a community of tropical trees may have evolved as an adaptation to reduce herbivory by insects.

Since then he has published more than 140 peer-reviewed articles. And, after Smithsonian and Fulbright postdoctoral fellowships in Panama and Colombia, respectively, he took a position at the University of Puerto Rico - Río Piedras in 1992, where he is now a full professor.

His research interests cover a diversity of topics related to tropical forest ecology, including plant/animal interactions, forest dynamics, population dynamics, restoration ecology, land change, community ecology, conservation, ecological informatics, and ecoacoustics. Presently, his research focuses on land-use change and its implication for biodiversity conservation.

“In addition to Mitch’s own scientific contributions,” wrote Coley in the nomination letter for the alumni award, Aide “has mentored an enormous number of students, most from Latin America. These include 18 Master’s students, 11 PhD students, over 50 undergraduates and eight postdoctoral fellows. His mentorship of the next generation of scientists has had profound impacts on education and conservation in Latin America.”

Aide has also started a company to monitor biodiversity. “This was motivated by his concern for the alarming loss of species in nature,” says Coley, before explaining that her former student’s innovation was to deploy many low-cost acoustic recorders in nature and then analyze the sounds to quantify changes in the community or to track individual species of interest.

“His company developed the sophisticated but user-friendly Automated Remote Biodiversity Monitoring Network (ARBIMON) platform so researchers can analyze these recordings for their own research,” continues Coley. “His goal is to have permanent acoustic biodiversity monitoring stations in thousands of sites throughout the world, including eco-tourism sites, research stations, protected areas, and threatened areas.”

A consummate researcher, academic and now founder of a company, Aide enjoys water sports, including surfing and snorkeling. After more than 40 years publishing on tropical ecology and conservation, and “seeing our poor progress in conserving tropical biodiversity,” he says with some rue, “I will try a different approach—write a novel.”

During this time of pandemic, personal and societal reflection is the order of the day. Aide expects that there will be substantial changes to higher education. Even so, he advises today’s students to “identify what you are good at and what you enjoy and dedicate 110%” to it.

As a 2021 SBS distinguished alumnus, Mitch Aide is an excellent model for dedication and hard work—even when pivoting late in an esteemed career towards fiction writing to further the cause of and raising consciousness about the critical need for conservation.

 
by David Pace
 

NAS Membership

April 28, 2021

mary beckerle elected to the national academy of science

The National Academy of Sciences has elected Mary Beckerle, PhD, Huntsman Cancer Institute (HCI) CEO and distinguished professor of biology and oncological sciences at the University of Utah (U of U), as a member. Beckerle is among 120 newly elected members announced in a press release during the annual meeting of the National Academy of Sciences.

Election as a member in this organization is widely accepted as a mark of excellence in scientific achievement and is considered one of the highest honors a scientist can receive. Of its more than 2,400 current members, approximately 190 have received a Nobel Prize, according to the National Academy of Sciences.

Beckerle shared she was “very surprised” to learn of her election to the prestigious group. She received a phone call this morning from a member of the National Academy of Sciences informing her of her election. Within minutes, she then received a flood of phone calls, emails, and text messages from colleagues congratulating her. “It was the most connected I have felt to my scientific community since the pandemic began, and it was lovely to be in touch with so many colleagues from around the world,” added Beckerle.

Beckerle’s research discovered a new pathway that is crucial in enabling cells to respond to mechanical signals in their environment. Such signals are now known to regulate cell growth and movement, two behaviors that yield critical insights into cancer biology. The Beckerle Lab is currently focused on understanding the molecular mechanisms underlying this pathway and its impact on tumor progression, particularly in Ewing sarcoma, a rare but deadly bone cancer that typically affects children and young adults.

“Dr. Beckerle’s election to the National Academy of Sciences affirms what her colleagues see every day. She is a driving force as an individual scientist, yet Dr. Beckerle’s hallmark is collaborative leadership that allows teams of scientists to achieve more together than they ever could alone,” said Michael L. Good, MD, University of Utah interim president and CEO of University of Utah Health. In addition to leading HCI, Beckerle holds the Jon M. Huntsman Presidential Endowed Chair and also serves as associate vice president for cancer affairs at the U of U. Beckerle is only the 27th faculty member in the history of the U of U to be elected to the National Academy of Sciences.

Beckerle joined the U of U faculty in 1986, when she set up her first independent laboratory as a young scientist. Prior to coming to Utah, she earned her PhD in molecular, cellular, and developmental biology from the University of Colorado at Boulder, where she received a Danforth Fellowship. She completed postdoctoral research at the University of North Carolina at Chapel Hill and received a Guggenheim Fellowship for her studies at the Curie Institute in Paris.

She has received numerous accolades for her research, including the National Cancer Institute Knudsen Prize in recognition of her contributions to research on the genetic basis of cancer. She is also an elected fellow of other distinguished scientific organizations, including the American Philosophical Society, the American Academy of Arts and Sciences, and the Academy of the American Association for Cancer Research.  She served as President of the American Society for Cell Biology and is a member of the Medical Advisory Board of the Howard Hughes Medical Institute.

As CEO of HCI, she led the organization to achieve its first-ever designation as a National Cancer Institute-Designated Comprehensive Cancer Center, the highest possible status of a cancer research institute. She also has led HCI’s clinical programs to recognition as among the nation’s Best Cancer Hospitals, according to U.S. News and World Report. Beckerle was appointed as a member of then-Vice President Biden’s Cancer Moonshot Blue Ribbon Panel, where she co-chaired the working group on Precision Prevention and Early Detection.

“It is an incredible honor to be named alongside exceptionally talented colleagues who are part of the National Academy of Sciences,” said Beckerle. “Scientific research is fascinating and motivating work, yet as a scientist, I often feel impatient. Each day, I work with the understanding that people are counting on the scientific community to make discoveries that will improve health, develop better treatments for diseases, enhance quality of life, and, wherever possible, prevent development of diseases like cancer. It is deeply humbling to see my contributions, and those of the many people who have worked in my lab over several decades, recognized in this way. My sincere hope is that the work of my research team will contribute to Huntsman Cancer Institute’s vision of delivering a cancer-free frontier.”

Beckerle adds that the National Academy of Sciences has a major impact in shaping science policy. She looks forward to the opportunity to contribute to the national dialogue on how to advance scientific innovation and impact via her role as a member of this organization.

first published by Ashlee Harrison of Huntsman Cancer Institute in @theU

Ace Madsen

April 5, 2021

Ace Madsen, MD

The Uinta Basin in the northeast corner of Utah can seem like a ways “out there” near the border of Colorado and one of the most famous dinosaur quarries in the world. In fact as of last month, says  Vernal-based Ace Arthur C. Madsen, BS’79, “it took six months for the pandemic to reach my corner of the state. Now I have two to three patients a week developing Covid-19 or succumbing to it. I believe the mask and hand sanitizer culture is here to stay.”

It’s a sobering reality for a rural and oil-industry region of the state next to some of the most beautiful and remote landscapes in the state, including Flaming Gorge and the Green River drainage as it flows toward its confluence with the Colorado to the south near Moab. But it is home for Dr. Madsen who has raised his family there and is now grandfather to a whopping fifteen grandchildren.

The University of Utah was the place for Madsen to chase his dream of becoming a doctor. Today he is in private practice in internal medicine. As an undergraduate he recalls Richard Van Norman who taught Botany as one of his favorite professors.“He was friendly, liked to spend one-on-one time with his students and seemed to really care about what we thought and our future plans.”

“My background in basic biological science, biochemistry and molecular biology provided me with a solid background and was invaluable to me in my research activities and medical school.” The Department of Biology, now the School of Biological Sciences, was a bit of a boot camp for him and other pre-med students.

“I am very grateful for the no nonsense approach” of many mentors, he says, including the late Gordon Lark, the late James L. Lords, and emeritus professors William R. Gray and Bob Vickery. Once Madsen had graduated in biology, the rigors of his training continued with the late Dr. Frank Moody and as a research assistant at the U’s Medical School in the departments of Pediatric Neurology with Drs. PF Bray and JT Wu as well as the Department of Surgery with Dr. Layton F. Rikkers, now an emeritus professor of surgery at the University of Wisconsin.

In 1981 Madsen graduated with his MD, receiving the Outstanding Research Award. During that time he secured eight publications and 10 abstracts, predominantly on oncofetal antigens such as carcino embryonic antigen (CEA) and alpha-fetoprotein (AFP). Following his graduation from the U Medical School he completed his residency in 1984 in Internal Medicine at Duke University.

Madsen isn’t the only alumnus in his family from the University of Utah. His wife Zoe graduated in mathematics with a minor in chemistry in 1975, and his son Adam earned his BS in biology in 2006 before following his father’s footsteps to medical school. While at the U, Adam, who quarterbacked for the Utes, was named Scholar-Athlete in the Mountain West Athletic Conference in 2004 and was part of the undefeated and Nationally-ranked Tostito’s Fiesta Bowl Champions football team in 2005.

Father (right, in photo above) and son both practice in Vernal.

In addition to his medical practice and his grandfathering, Madsen works in wood and stained glass as hobbies. When asked what advice he would give to current students in the School of Biological Sciences, he is succinct and quick to number what he thinks future graduates from the U should do. 1. “Study hard. It is difficult to get anywhere without good grades. 2. Get involved with research. 3. Get married--best move I made in life.”

 

By David Pace

Are you a Science Alumni? Connect with us today!