A Framework for Cancer Ecology and Evolution

A Framework for Cancer Ecology and Evolution


July 17, 2024

Why do the vast majority of cancers arise late in subjects’ lives?

A traditional explanation in the development of cancers, known as the somatic theory, is a paradigm focused on mutations in individual cells. In this theory a cascade of approximately six mutational changes in a single cell is the source that triggers cancer.  This theory explains the rapidly increasing “power function” that describes how cancer incidence increases with age.

But this power function which lines up with cancer’s six classic hallmarks is now being challenged by a different paradigm that casts doubt on the primacy of individual cells in cancer development. It also challenges the notion that cancer marks a strict change between “normal” and aberrant tissues, particularly as the body ages.

In a paper published today in The Royal Society Interface out of the United Kingdom, “A modeling framework for cancer ecology and evolution” is explored by University of Utah mathematics professor Frederick Adler with a joint appointment in biology.

Cancer's complexity

Fred Adler. Credit: Matt Crawley

Adler says he has struggled for a long time to come up with an alternative modeling approach for cancer that has the flexibility to capture the complexity of cancer, while standing by the dictum that cancer cells are still cells. “It involved a plane trip where I worked out an extremely complicated approximate version of the method before figuring out, on solid ground, that the exact version was thoroughly simple.” 

Simple didn’t just mean elegant, but also getting results in a reasonable amount of time by optimizing code, something he can appreciate as the current Director of the busy School of Biological Sciences, one of the largest academic units at the University of Utah. 

Adler’s findings build on those of others that countermand the primacy of individual cells. These include observations of mutations common in non-cancerous tissues, and sometimes more common than in nearby cancers. “This implies,” the paper states, “that cancers depend on interactions with the surrounding tissue.” A second emphasis on cancer ecology and evolution is now highlighting “the ecology of nutrients, acids and physical factors and the role of cell interactions.”

“Detailed study of adults shows that few if any of their cells are ‘normal,’” says Adler. “Tissues are instead made up of lineages with ever-increasing numbers of aberrant traits, many of which promote excess growth. The vast majority of these incipient growths are contained by controls within those cells and by other cells.”

In Adler’s parsing of the ecological paradigm, senescence theory plays a critical role, focusing on the breakdown of the system of controls within and around individual cells. “[M]any cancers,” for example, “develop much later than their originating oncogenic mutations.” Furthermore, mutant cells in his models are restrained “by systems that remove their growth advantage, but which can weaken with age due to changes such as impaired intercellular communication. Remarkable data on genetic diversity in healthy tissues show that cancer-related mutations are ubiquitous, and often under positive selection despite not being associated with progression to cancer.”

Overview of CAGRM framework. Cells include an arbitrary number of potential lineages, beginning with all cells in the unmutated lineage C0 and evolving first into C1 and eventually a branching evolutionary tree of lineages here indicated collectively by Ci. There are four forms of regulation (indicated by flat-headed arrows): contact inhibition by other cells (C ), inhibition by antigrowth factor (A), depletion of growth factor (G) and depletion of resources (R). Mutualist cells can aid cell replication by suppressing antigrowth factor or by supplementing growth factor or resources.

Tracking the dual nature of cells

In the paper, Adler first presents a modeling framework which incorporates evolution, stochasticity (a measure of how random a process is, or the quality of lacking a predictable order or plan) and control and breakdown of control. Using a differential equation, the model then tracks the dual nature of individual cells as ecological competitors for resources and space. 

Using this framework Adler then tested whether the ecological model of cancer initiation generates realistic age-incidence patterns similar to the somatic mutation theory. Another test was made to determine how initial defects in the control systems accelerate the process. 

In this comprehensive systems view, cancer, and an incipient cancer in particular, is not an invader. “It is a set of cells,” the paper reads, “that escape the many layers of internal and tissue level regulation, and then grow to damage the host. The success of a cancer, or equivalently the failure [emphasis added] of the regulatory system, requires that the cancer co-opts or evades the systems of control and repair.”

This model/framework, according to the author, assumes a particular structure of the control system but has capacity for “several other extensions” to make it more “realistic.” Those extensions would address, for example, cell differentiation and a clearer class of driver mutations for the genetic model of quantitative trait. Another might address why the mutualist cells in the tests maintain a constant phenotype in spite of what we know about how cells alter behavior in cancer’s presence.

Statistically, we understand that cancer emerges more frequently in older individuals. But how and why is what Adler is attempting to determine. His model, says Adler, “reproduces the rapid increase of cancer incidence with age, identifies the key aspects of control, and provides a complement to the focus on mutations that could lead to new treatment strategies.”

Fred Adler points out that the control system in the model differs greatly across species in concert with their body size and lifespan, thus revealing a paradox known as Peto’s:  cancer rates are similar across organisms with a wide range of sizes and lifespan. “This robustness,” concludes the paper, “is a special case of the principle that all biological systems must be overbuilt to deal with uncertainty.” Referencing Shakespeare’s Hamlet, Adler states that this development in excess of demand exists “to survive ‘the thousand natural shocks that flesh is heir to’… This model seeks to place those shocks in the ecological and evolutionary context that makes long life possible.” 

 

by David Pace

Read about Fred Adler's related work in modeling cancer development, specifically with breast cancer.

 

Journey to the Center of Biotech

Journey to the Center of Biotech 


July 8, 2024
Above: Heng Xie

“I guess I just can’t help being a visionary,” Heng Xie jests, reflecting on her career since leaving academia. 

Xie earned her PhD in biology from the University of Utah in 2004 and where she remained as a postdoc for several years. At the time, she never imagined herself working industry. Yet to her surprise, she amassed extensive experience in biotechnology. In her first foray from academia, she taught eighth-grade science and helped build the charter school’s AP biology program.

While she loved teaching, Xie always felt the urge to venture out and gain experience in molecular biology which she also enjoyed. As such, new technological developments in a local biotechnology startup, IDbyDNA, presented her call to action. She recalls “the startup company was pushing for a new technology that was obviously going to be the future. Now the question was, who was going to make it a reality? Why not us?”

To finally embrace the uncertainty of industry was scary, but Xie knew this was her time to act. “I can always go back to teach, but this leap of faith, if I didn’t take it, I may not have another opportunity,” she says. In fact, while learning new skills herself, she never stopped teaching and mentoring others. 

Hypothesis-free Diagnostics

IDbyDNA is a local metagenomics company with an innovative algorithm that simultaneously profiles tens of thousands of microorganisms (or pathogens) in any sample by massive parallel sequencing, known as Next Generation Sequencing (NGS). Xie says this technology is fundamentally different from other available tests because it is hypothesis-free. “We’re not making any guesses, educated or not; we just treat everybody the same, and we sequence everything in there. And by analyzing the sequence in the sample, bioinformatics can tell you what it is. You don’t have to say ‘Tell me if it’s the flu.' It will tell you, ‘No, it’s not the flu, it’s something else.’” 

By taking this approach to diagnosis, IDbyDNA circumvents two major problems. “The first issue is [the] diversity of the potential cause of the disease. The second issue is [one of timing as] some of the really dangerous pathogens that cause diseases such as tuberculosis, can take a long time to grow. By the time you can actually grow it and identify it, the patient's disease has progressed, and, [by then,] they might have been in the ICU for weeks.” 

Hybrid Capture

Though these major concerns were sidestepped, other problems became apparent. “One problem we saw at IDbyDNA was when you get a patient sample and you start to sequence the DNA, the majority of the DNA is the host DNA because the human genome is orders of magnitude larger than the pathogen genome,” explains Xie. “Even a single human cell is going to give you much more sequencing information than the pathogen. So, you actually are not going to have the level of sensitivity you want for it to be clinically applicable.”

To bypass this problem, one can enrich the pathogen signal by selectively pulling the pathogen sequences (with complementary DNA) from the sample before analyzing. The challenge here is that the diversity of the pathogens would require extremely high complexity capturing, which means high-complexity DNA synthesis.

At IDbyDNA, Xie started as a research scientist, co-developing the Explify® clinical diagnostic platform and left as an associate director after six years. The company was eventually acquired by Illumina, a giant sequencing company. 

Her next adventure in industry after IDbyDNA was as principal scientist at GenScript, a company that develops and manufactures gene synthesis products and services used by researchers in academia, pharmaceutics and biotech. Xie joined the Seattle campus because of the CustomArray technology that synthesizes millions of different DNA molecules on a semiconductor chip. This high-complexity, low-cost production of DNA became the natural extension of Xie’s earlier interest.  

“When I went there [Genscript], this was pre-production, and I helped them evaluate and quantify how good they are and help them improve the product,” says Xie. Her work over nine months resulted in reduced costs and streamlined application of NGS technology in product development. 

Precision Oncology

From GenScript, Xie took the position of senior director of pharma services at NeoGenomics Laboratory, a company dedicated to precision oncology. This newest endeavor is the perfect combination of her other experiences: a hypothesis-free approach applied with hybrid sequencing technology that can provide targeted therapies for cancer patients. At NeoGenomics, biopsies of tumors are sequenced and matched back to the mutation that caused them.

“Then, if the clinician needs to target the specific cancer, they can select suitable drugs that have been approved or are in clinical trials to [make a] recommendation to the patient based on the sequencing results.” This highly targeted therapy means that the patient doesn't have to suffer general chemo, Xie says. She and her team have launched several impactful tests since she joined NeoGenomics. More exciting tests are getting ready for the market. 

Accelerating the pace

It took a while for Xie to leave academia, but she hasn’t looked back since. She has been dedicated to accelerating the pace in the biotech industry, making innovations at the top of the supply chain that impact research in industry and academia further down, or serving patients with state-of-the-art diagnostic technologies. While earning her PhD at the U, Xie never imagined the exciting career she would create for herself. 

“[W]hat I absorbed in school was that there is no value outside academia because everything else is not as scientifically rigorous and not as innovative, not as cutting edge, not at the very boundary of human knowledge.” 

But Heng Xie’s success at all levels of the biotech industry is living proof of the abundant exciting opportunities students have and a testament to the growth of science beyond academia. Her experiences showcase how rigorous research in academia impacts society through the commercialization of innovative technologies. 

by Lauren Wigod 

Delve into the puzzle of ice crystallization and uncover its secrets.

Delve into the puzzle of ice crystallization and uncover its secrets


July 5, 2024
Above: A screen capture from a slow-motion movie covers mere nanoseconds — when water is tuned to a critical point called the liquid-liquid transition.

Making ice requires more than subzero temperatures. The unpredictable process takes microscopic scaffolding, random jiggling and often a little bit of bacteria.

We learn in grade school that water freezes at zero degrees Celsius, but that’s seldom true. In clouds, scientists have found supercooled water droplets as chilly as minus 40 C, and in a lab in 2014, they cooled water to a staggering minus 46 C before it froze. You can supercool water at home: Throw a bottle of distilled water in your freezer, and it’s unlikely to crystallize until you shake it.

Freezing usually doesn’t happen right at zero degrees for much the same reason that backyard wood piles don’t spontaneously combust. To get started, fire needs a spark. And ice needs a nucleus — a seed of ice around which more and more water molecules arrange themselves into a crystal structure.

Valeria Molinero, a physical chemist at the University of Utah, builds computer simulations of water to study ice nucleation.

The formation of these seeds is called ice nucleation. Nucleation is so slow for pure water at zero degrees that it might as well not happen at all. But in nature, impurities provide surfaces for nucleation, and these impurities can drastically change how quickly and at what temperature ice forms.

For a process that’s anything but exotic, ice nucleation remains surprisingly mysterious. Chemists can’t reliably predict the effect of a given impurity or surface, let alone design one to hinder or promote ice formation. But they’re chipping away at the problem. They’re building computer models that can accurately simulate water’s behavior, and they’re looking to nature for clues — proteins made by bacteria and fungi are the best ice makers scientists know of.

Understanding how ice forms is more than an academic exercise. Motes of material create ice seeds in clouds, which lead to most of the precipitation that falls to Earth as snow and rain. Several dry Western states use ice-nucleating materials to promote precipitation, and U.S. government agencies including the National Oceanic and Atmospheric Administration and the Air Force have experimented with ice nucleation for drought relief or as a war tactic. (Perhaps snowstorms could waylay the enemy.) And in some countries, hail-fighting planes dust clouds with silver iodide, a substance that helps small droplets to freeze, hindering the growth of large hailstones.

But there’s still much to learn. “Everyone agrees that ice forms,” said Valeria Molinero, a physical chemist at the University of Utah who builds computer simulations of water. “After that, there are questions.”

You can read the full story in Quanta magazine. Read the published research @PNAS.

Life On Other Planets … and in a student’s mind

Life On Other Planets … and in a student’s mind


June 13, 2024
Above: Mary Fairbanks BS'23, biology

A DNA repair system known as the GO DNA repair system removes oxidized guanine. This helps protect the system from mutating, and while scientists understand how it works, the origin of this mechanism isn’t well understood.

That’s where the Martin Horvath Lab comes in and, in particular, Mary Fairbanks BS’23. She and her team in the School of Biological Sciences at the University of Utah explore structural biology and biochemistry by researching microbes from the Lost City Hydrothermal Field, an area of marine alkaline hydrothermal vents located in the Atlantic Ocean. 

As with Fairbanks, who gained hands-on experience creating experiments and directly participating in research, other lab members worked on the project as undergraduates before graduating. They include Payton Utzman BS’22 and Briggs Miller BS’22 who along with Fairbanks and graduate student Vincent Mays researched microbes that live at the bottom of the ocean where there is little oxygen and even less sunlight. Because of the lack of oxygen in the environment where these microbes thrive, the fact that researchers found GO DNA repair genes is important: it shows a need for genes that repair DNA that has been put under stress from oxygen. Their research was recently published in PLOS

Acting like a scientist

"Working in Dr. Horvath’s lab has taught me how to be curious and be dedicated to a project,” says Fairbanks. “Being able to design my own experiments has given me the opportunity to act as a scientist. I have grown through research and it continues to expand my view of the possibilities of innovation.” 

Horvath first learned that one of the GO repair genes called MutY might be present at the Lost City Hydrothermal Field from a student in his Molecular Biology of DNA Lab course, Emily Dart HBS’16. Horvath knew that Dart was working with William Brazelton, a fellow biologist who had recently collected DNA from Lost City. Searching that Lost City DNA, Dart and her teammates found genes encoding at least portions of MutY.

“Since that first analysis,” says Horvath, “the sequence technology improved, more samples from another expedition generated metagenomes with better coverage, and we now have functional tests that show these MutYs from the bottom of the ocean actually work to prevent mutations in lab strains of bacteria.” That these discoveries stemmed from basic science research by undergraduates, he says, is “something that I am very proud to celebrate!”

How life might evolve on other planets

GO DNA repair genes are advantageous even in environments without much oxygen. Since hydrothermal fields like the Lost City Hydrothermal Field are similar to the environment of early Earth, this indicates that these repair systems evolved before the Great Oxidation Event.

Fig 5. LCHF MutY chemical motifs. (A) Conservation and diversity of MutY-defining chemical motifs are depicted with a sequence logo for the 160 LCHF MutYs. These motifs are associated with biochemical functions including DNA binding, enzyme catalysis, attachment of the iron-sulfur cofactor, and recognition of the damaged OG base.

Insights like this can help develop models of how life might evolve on other planets. Planets that lack the abundance of oxygen that modern Earth has may have life evolving in a similar way to microbes that live near hydrothermal vents. Since these microbes have repair systems that deal with oxidative stress, it’s reasonable to consider that life on other planets may as well.

The group also discovered the role that these repair genes, including MutY, play in hydrothermal microbes, by associating GO DNA repair with metabolic pathways. These pathways produce oxygen as a byproduct, so MutY may play a part in fixing DNA damage caused by metabolic processes.      

Life on other planets may take many different forms, and similarly, learning science also takes many forms beyond the classroom. “I’ve been encouraged to ask questions and explain findings to form a cohesive pattern that tells a story,” says Fairbanks. She credits the lab experience as helping her “see a project from start to finish. I have been able to improve my critical thinking skills and laboratory technique, as well as adapt to change.” 

That adaptation to change is a good lesson to learn as empirically observed far below the surface of the ocean but also on a personal level for Fairbanks and her young researcher cohorts. Findings such as these may show how DNA-based life forms rely on fixing damage caused by oxidation, even in environments without oxygen. And they give scientists a clue as to how life may look on other planets by forming models of life in environments unlike Earth’s. But the “findings” are clearly internal as well for young, developing scientists who will never forget their time examining and interpreting data in the Horvath Lab. 

As Martin Horvath intones of this research, “Life finds a way.” 

As do young minds like that found embodied in Mary Fairbanks who, now headed for a career in the medical field, concludes, “I believe my experience in research will make me a more open-minded thinker.”

by CJ Siebeneck

Meet Lokiceratops: Giant Blade-Wielding Dinosaur


Meet Lokiceratops:
A Giant Blade Wielding Dinosaur


June 21, 2024
Above: Reconstruction of Lokiceratops surprised by a crocodilian in the 78-million-year-old swamps of northern Montana, USA.
Image ©Andrey Atuchin for the Museum of Evolution in Maribo, Denmark.

A remarkable, new species of horned, plant-eating dinosaur is being unveiled at the Natural History Museum of Utah. The dinosaur, excavated from the badlands of northern Montana just a few miles from the USA-Canada border, is among the largest and most ornate ever found, with two huge blade-like horns on the back of its frill. The distinctive horn pattern inspired its name, Lokiceratops rangiformis, meaning “Loki’s horned face that looks like a caribou.” The study included the most complete analysis of horned dinosaur evolution ever conducted, and the new species was announced today in the scientific journal PeerJ.

More than 78 million years ago, Lokiceratops inhabited the swamps and floodplains along the eastern shore of Laramidia. This island continent represents what is now the western part of North America created when a great seaway divided the continent around 100 million years ago. Mountain building and dramatic changes in climate and sea level have since altered the hothouse world of Laramidia where Lokiceratops and other dinosaurs thrived. The behemoth is a member of the horned dinosaurs called ceratopsids, a group that evolved around 92 million years ago during the Late Cretaceous, diversified into a myriad of fantastically ornamented species, and survived until the end of the time of dinosaurs. Lokiceratops (lo-Kee-sare-a-tops) rangiformis (ran-ɡi-FOHR-mees) possesses several unique features, among them: the absence of a nose horn, huge, curving blade-like horns on the back of the frill—the largest ever found on a horned dinosaur—and a distinct, asymmetric spike in the middle of the frill. Lokiceratops rangiformis appeared at least 12 million years earlier than its famous cousin Triceratops and was the largest horned dinosaur of its time. The name Lokiceratops translates as “Loki’s horned face” honoring the blade-wielding Norse god Loki. The second name, rangiformis, refers to the differing horn lengths on each side of the frill, similar to the asymmetric antlers of caribou and reindeer.

PHOTO CREDIT: MARK LOEWEN.
Completed reconstruction of Lokiceratops mounted for display. Study authors Brock Sisson (left) and Mark Loewen (right) peer through the frill fenestrae (windows) of Lokiceratops.

Lokiceratops rangiformis is the fourth centrosaurine, and fifth horned dinosaur overall, identified from this single assemblage. While ceratopsian ancestors were widespread across the northern hemisphere throughout the Cretaceous period, their isolation on Laramidia led to the evolution of huge body sizes, and most characteristically, distinctive patterns of horns above their eyes and noses, on their cheeks and along the edges of their elongated head frills. Fossils recovered from this region suggest horned dinosaurs were living and evolving in a small geographic area—a high level of endemism that implies dinosaur diversity is underestimated.

“Previously, paleontologists thought a maximum of two species of horned dinosaurs could coexist at the same place and time. Incredibly, we have identified five living together at the same time,” said co-lead author Mark Loewen, a paleontologist at the Natural History Museum of Utah and professor in the Department of Geology & Geophysics at the University of Utah. “The skull of Lokiceratops rangiformis is dramatically different from the other four animals it lived alongside.”

The fossil remains of Lokiceratops was discovered in 2019 and cleaned, restored and mounted by Brock Sisson, paleontologist and founder of Fossilogic, LLC in Pleasant Grove, Utah. “Reconstructing the skull of Lokiceratops from dozens of pieces was one of the most challenging projects my team and I have ever faced,” said Brock, “but the thrill of bringing a 78-million-year-old dinosaur to life for the first time was well worth the effort.”

Discover more about Lokiceratops by visiting the full article by Mark Loewen at @The U.
Read more about the story in Discover Magazine, ABC 4 News, KSL News, Science Daily, Science News.

Utah’s fir trees at risk from balsam woolly adelgid

Utah's fir trees at risk from
balsam woolly adelgid


June 20, 2024
Above: A drone photograph in Farmington Canyon shows the several level of infestation of balsam woolly adelgid infesting subalpine fir.
PHOTO CREDIT: MICKEY CAMPBEL

A nonnative tree-killing insect is invading northern Utah, attacking subalpine fir and potentially triggering yet another die-off of the region’s long-stressed conifer forests.

Introduced from Europe into the Pacific Northwest about a century ago, the balsam woolly adelgid (BWA), or Adelges piceae, was first detected in Utah in 2017 and has been spreading around the Wasatch Mountains, visibly affecting many of the popular recreation canyons outside Salt Lake City.

New research from the University of Utah, conducted in partnership with the U.S. Forest Service, has documented the current extent of the adelgid infestation and created a model for predicting its severity around the Uinta-Wasatch-Cache National Forest.

The study documented a clear relationship between the infestation’s severity and temperature, according to lead author Mickey Campbell, a research assistant professor in the Department of Geography (soon to be merged with the Environmental Studies program and renamed the School of Environment, Society, and Sustainability.)

PHOTO CREDIT: MICKEY CAMPBELL The crowns of infested fir trees exhibit crown deformities.

“We took that climate-to-severity relationship along with a series of climate projections and we were able to map current and future exposure to BWA damage at a high spatial resolution,” Campbell said. “The idea [is], in 2040, 2060, 2080 and 2100, based on these different climate projections, determining how exposed these areas are to the potentially damaging effects of BWA. And indeed, we find that for an insect that prefers warmer areas, a warming climate is going to provide it with more opportunity to cause damage.”

The role of climate change

The study appears this month in the journal Forest Ecology and Management. Co-authors include U Biology Professor William Anderegg, director of the Wilkes Center for Climate Science and Policy. [The center hosts its annual Climate Summit on May 14-15, where Anderegg will give opening remarks.]

According to Anderegg, the new study suggests climate change is playing a role in Utah’s adelgid infestation.

“The main pieces of evidence are how strongly temperature is related to the spread and severity of BWA,” said Anderegg, a specialist in forest ecology. “That tells us at the very least as temperatures go up, we should be concerned about more spread and higher severity infestation.” Covering the Wasatch, Uinta, Bear River and a few lesser mountain ranges in northern Utah, this national forest is among the nation’s busiest for recreation. It features five major ski areas that border several others and sees more visits than all of Utah’s national parks combined.

Read the full article by Brian Maffly at @TheU.

Hear the Interview of Dr. Mickey Campbell ( Lead Author and research assistant professor in the Department of Geography) with Ross Chambless on the spread of balsam woolly adelgid in Utah on The Wilkes Center for Climate Science & Policy page.

Bacteriophages: Nature’s bacterial killers

Bacteriophages : Nature's bacterial killers


June 14, 2024
Above: Talia Karasov

Bacteriophages, viruses that attack and destroy bacteria, are everywhere in the natural world where they play a vital role in regulating microbe populations in ways that are not yet well understood.

New research led by the University of Utah and University College London (UCL) has found that plant bacterial pathogens are able to repurpose elements of their own bacteriophages, or phages, to wipe out competing microbes. These surprise findings suggest such phage-derived elements could someday be harnessed as an alternative to antibiotics, according to Talia Karasov, an assistant professor in the U’s School of Biological Sciences.

This result was hardly what she expected to find when she embarked on this research with an international team of scientists. Microbial pathogens are all around, but only a fraction of the time do they sicken humans, other animals or plants, according to Karasov, whose primary research interest is in interactions between plants and microbial pathogens. The Karasov lab is seeking to understand the factors that lead to sickness and epidemics versus keeping the pathogens in check.

“We see that no single lineage of bacteria can dominate. We wondered whether the phages, the pathogens of our bacterial pathogens, could prevent single lineages from spreading – maybe phages were killing some strains and not others. That’s where our study started, but that’s not where it ended up,” Karasov said. “We looked in the genomes of plant bacterial pathogens to see which phages were infecting them. But it wasn’t the phage we found that was interesting. The bacteria had taken a phage and repurposed it for warfare with other bacteria, now using it to kill competing bacteria.”

A thale cress specimen collected in 1866 in Germany and preserved in a herbarium in Tubingen. Credit: Burbano lab, University College London.

Mining herbarium specimens for their microbial DNA

Burbano has pioneered the use of herbarium specimens to explore the evolution of plants and their microbial pathogens. His lab sequences the genomes of both host plants and those of the microbes associated with the plant at the time of collection more than a century ago.

For the phage research, Burbano analyzed historical specimens of Arabidopsis thalianaa plant from the mustard family commonly called thale cress, collected in southwestern Germany, comparing them and the microbes they harbored to plants growing today in the same part of Germany. Lead author Talia Backman wonders if tailocins could help solve the impending crisis in antibiotic resistance seen in harmful bacteria that infect humans.

“We as a society are in dire need of new antibiotics, and tailocins have potential as new antimicrobial treatments,” said Backman, a graduate student in the Karasov lab. “While tailocins have been found previously in other bacterial genomes, and have been studied in lab settings, their impact and evolution in wild bacterial populations was not known. The fact that we found that these wild plant pathogens all have tailocins and these tailocins are evolving to kill neighboring bacteria shows how significant they may be in nature.”

Discover the full story behind bacteriophages and their antibiotic potential by Brian Maffly at @The U. More on this story at earth.com.

Championing Representation & Advocacy in Healthcare

Championing Representation & Advocacy in Healthcare


June 12, 2024
Above: Kimberly Gamarra

Kimberly Gamarra, a graduate of the University of Utah’s School of Biological Sciences, was recently accepted to the U’s Spencer Fox Eccles School of Medicine. While Gamarra has been successful in her pursuit of her goals to work in the medical field,  her journey has been fraught with challenges.

 

Participating in the English as a Second Language (ESL) Express Registration event at SLCC as a peer mentor leader.

Gamarra’s exciting educational milestone boils down to personal triumph, mentorship, and resilience. Navigating her family’s adopted home of the U.S., she began her undergraduate studies early during high school, completing concurrent enrollment classes through Salt Lake Community College before finishing her degree at the U.

In the university setting Gamarra found guidance and community through the Refugees Exploring the Foundations of Undergraduate Education In Science (REFUGES) Bridge Program (REFUGES), designed to support students with tools for college and career readiness. Founded by physics faculty member Tino Nyawelo, the program proved to be a pivotal support system for Gamarra. “From the start, I've always wanted to do medicine," she reflects. “That was my goal. And so having Tino’s program, there was a huge help in acclimating to the new campus and getting to know faculty, staff, and other students. And it really helped me network really well from the start, and feel more comfortable.” Through the program, she not only found her footing in the academic landscape but also discovered her capacity for leadership and mentorship, being able to give back as a science and mathematics tutor.

Gamarra is quick to open up about her upbringing and how her family’s challenges during her childhood impacted her present journey: “My parents are immigrants from Peru and their transition to the U.S, especially navigating healthcare, was a challenge. I suffered from a brain tumor as a child, so a big motivation for them moving to the U.S. was to make sure I received the best treatment possible. This whole process opened my eyes to the strengths and struggles of our current healthcare system, and ways I can help make it better.” 

Drawing from her family's experiences, Gamarra is prepared to think beyond traditional healthcare expectations by providing care for her future patients on more than just a physical level, emphasizing the importance of equity, inclusion, and community on health and well-being. She has been involved in several projects that provide guidance to Latinx families about free health-related resources and volunteers her time as a Spanish and English translator. Her interactions with patients, families and mentors are what fueled her determination to continue pursuing medicine. She is particularly interested in helping foster a greater sense of trust between physicians and their patients, which she sees as key to success. 

At the Mitaka Picture Book initiative in Japan, reading Spanish to Japanese children and their families.

Transcending cultural and linguistic barriers

With an interest in global health and social justice, Gamarra envisions a career that transcends borders and barriers. In her final year at the U, she attended the Oxford Consortium for Human Rights based in the UK, where she drew a strong parallel between health and human rights. With her group she presented on climate refugees and the barriers to accessing healthcare, as well as discussing health from a cultural point of view considering the existence of traditional medicine. Upon returning to Utah, she helped create the podcast RadioNatura, opening up these discussions to a global audience. This commitment to removing cultural and linguistic barriers defines Gamarra's vision for her future in medicine. 

With a degree in biology and a minor in pediatric clinical research, Gamarra will begin medical school this August with an interest in pediatrics. She hopes to expand on her expertise and knowledge: “Presenting different studies that doctors in the University of Utah health community are doing really opened my eyes to the vulnerability of children,” she states. “I see the field of pediatrics as a promising one because I can have a long-term impact and build strong relationships with families, providing comprehensive care that considers the well-being of both the child and the family unit.” 

‘Doing More’ is a subjective term

Though Gamarra has experienced many ups and downs on her path, she has always remained focused on her goals. “I would be lying if I said this whole journey was smooth,” she admits. “It was actually extremely rocky. There were times I doubted myself because there was always a thought in my mind that I could be doing more. But I realized that ‘more’ is subjective. It is less about accumulating experiences and more about the reflections and growth that comes out of those experiences.” While Gamarra admits that she once admired people with busy calendars, she no longer glamorizes it: “Being ‘busy’ without time to self-reflect is not the path I want to take in my life.”

As she prepares to embark on the next chapter of her life — medical school — Gamarra carries with her the support of those who helped her along the way. “I just focus on the people that were there for me, and I think that because of the REFUGES Program, Tino is a wonderful person that was there for me. He was someone that saw me through this journey, and that is still with me through this next journey, which I value a lot.” 

In Kimberly Gamarra, the U’s School of Medicine has found more than just a future doctor, but an individual who will undoubtedly create change and strengthen communities wherever she goes.

By Julia St. Andre

Finding new ant species in a SLC backyard

Utah’s ant man found a new species in his backyard


June 5, 2024
Above: John "Jack" Longino, in the tropics

University of Utah professor Jack Longino’s research mainly takes him to Central America, but on the weekend he collects and examines the diverse ant species around him.

Jack Longino likes to spend his weekends close to the ground. He often wears a vest that holds fifteen tiny vials filled with alcohol and a backpack with about 100 more.

“People look at me and they think I’ve got a bullet belt,” he said.

Longino uses the vials to carefully collect and preserve ants. “I end up with thousands of tiny little bottles of alcohol with dead ants in them,” he said.

He has traveled and documented ants extensively in Central America, but Longino is “interested in ant diversity anywhere I am.”

Luckily, ants are just about everywhere and each zone — from the marshes of the Great Salt Lake to high elevation Alta to the West Desert — has its own set of species.

In 2018 Longino was hanging out in the backyard of his Salt Lake City home when he noticed an unusual group of ants normally found in tropical habitats. Very few of that particular species were recorded in the Western U.S. At first he assumed they had come from Southern Arizona, perhaps hitched a ride on potting soil.

Read the full article by reporter Sofia Jeremias in the Salt Lake Tribune. (Pay wall)

A Tale of Two Worms: Advancing Epigenetics

A Tale of Two Worms : Advancing Epigenetics


June 4, 2024
Above: Immunofluorescence in round worm. Credit: Audrey Brown

Why an important epigenetic gene is missing in some species of roundworm.


by Audrey Brown
Graduate Student, School of Biological Sciences

Have you ever wondered how a cell knows whether it’s supposed to be skin or muscle? Or philosophized about “nature vs. nurture,” that is, how contributions from both genetics and the environment influence physical phenotypes? Epigenetics, a relatively new field in biology, helps explain the mechanistic basis for this phenomenon—and is the field I have chosen to dedicate my doctoral studies at the University of Utah.

Audrey Brown

I sometimes find the easiest way to describe epigenetics is using a metaphor. Imagine that the DNA within a cell is an instruction manual. It contains all the instructions necessary for cellular functions — but this manual can also be modified. Epigenetic modifications (“epi” meaning “on top of”) are like “sticky-notes,” a set of additional instructions on top of the manual. These notes contain directions like “make more of this gene here” or “turn this gene off completely.” In reality, these notes take the form of chemical tags added to the DNA itself or to proteins associated with the DNA. Scientists like myself and my colleagues in Michael Werner’s lab at the School of Biological Sciences are trying to understand what type of information each of these modifications encodes, and how the set of modifications is changed by external environmental factors.

I recently co-authored a paper in Genetics addressing this last pointFor this study, we created and compared lists of all the epigenetic genes present in these two worms. For the most part they contained a similar repertoire of epigenetic genes, yet we found one striking difference: P. pacificus is missing an epigenetic protein complex called PRC2. This was a surprising result since PRC2 is one of the most conserved epigenetic protein complexes, and is essential for various cellular functions, including cell differentiation and gene repression. So how is P. pacificus able to survive without it? We found one clue with the help of Ofer Rog’s lab at the U. We were able to detect the enzymatic output of the PRC2 complex (i.e. the specific “sticky-note” it writes), which led us to conclude that a different, yet unknown enzyme has taken over the function of PRC2 in P. pacificus.

Read more of Audrey Brown's article about these advancements in epigenetics in @The U.