For a while, crocodile

For a while, crocodile


April 17, 2024
Above:  Some 215 million years ago in what is now northwestern Argentina, the terrestrial crocodylomorph Hemiprotosuchus leali prepares to devour the early mammal relative Chaliminia musteloides. Credit: Jorge Gonzalez

The ancestors of today’s crocodylians survived two mass extinction events. A new study uncovered a secret to their longevity, which could help conservationists better protect our planet’s most vulnerable species.

Keegan Melstrom, assistant professor, University of Central Oklahoma with three crocodylomorphs. Photo credit: University of Central Oklahoma

Most people think of crocodylians as living fossils— stubbornly unchanged, prehistoric relics that have ruled the world’s swampiest corners for millions of years. But their evolutionary history tells a different story, according to new research led by the University of Central Oklahoma (UCO) and the University of Utah.

Crocodylians are surviving members of a 230-million-year lineage called crocodylomorphs, a group that includes living crocodylians (i.e. crocodiles, alligators and gharials) and their many extinct relatives. Crocodylian ancestors persisted through two mass extinction events, a feat requiring evolutionary agility to adapt to a rapidly changed world. The study’s authors discovered that one secret to crocodylian longevity is their remarkably flexible lifestyles, both in what they eat and the habitat in which they get it.

“Lots of groups closely related to crocodylians were more diverse, more abundant, and exhibited different ecologies, yet they all disappeared except these few generalist crocodylians alive today,” said Keegan Melstrom, lead author and assistant professor at UCO, who began the research as a doctoral student at the U. “Extinction and survivorship are two sides of the same coin. Through all mass extinctions, some groups manage to persist and diversify. What can we learn by studying the deeper evolutionary patterns imparted by these events?”

Earth has experienced five mass extinctions in its history. Experts argue that we’re living through a sixth, driven by habitat destruction, invasive species and changing climates. Identifying traits that boost survivorship during planetary upheaval may help scientists and conservationists better protect vulnerable species today.

Historically, the field has regarded mammals as the poster children for understanding mass extinction survival, lauding their generalist diet and ability to thrive in different ecological niches. Despite their resilience, research has largely ignored the crocodylomorph clade. The paper, published on April 16 in the journal Palaeontology, is the first to reconstruct the dietary ecology of crocodylomorphs to identify characteristics that helped some groups persist and thrive through two mass extinctions—the end-Triassic, about 201.4 million years ago (Ma), and the end-Cretaceous, about 66 Ma.

There’s a danger of trying to draw conclusions from millions of years ago and directly apply it to conservation. We have to be cautious,” said co-author Randy Irmis, curator of paleontology at the Natural History Museum of Utah and professor in the U’s Department of Geology & Geophysics. “If people study mammals and reptiles and find the same patterns with respect to extinction survival, then we might predict that species with a generalist diet may do better. That information helps us make predictions, but it’s unlikely we’ll ever be able to pick out which individual species will survive.”

A hidden past of alternative lifestyles

Randy Irmis faces off with a fossil Borealosuchus skull from the Natural History Museum of Utah’s collections. This crocodylian lived approximately 48 million years ago in the American West. Photo credit: Jack Rodgers/NHMU

Living crocodylians are famous for being semi-aquatic generalists that thrive in environments like lakes, rivers or marshes, waiting to ambush unsuspecting prey. Picky eaters, they are not. Young ones will snack on anything from tadpoles, insects or crustaceans before graduating to bigger fare, such as fish, baby deer, or even fellow crocs. Yet the uniform lifestyle of today’s crocodylians masks a massive diversity of dietary ecologies in which past crocodylomorphs thrived.

During the Late Triassic Period (237–201.4 Ma) Pseudosuchia, a broader evolutionary group that includes early crocodylomorphs and many other extinct lineages, ruled the land. The earliest crocodylomorphs were small-to-medium-sized creatures that were rare in their ecosystems, and were carnivores that mostly ate small animals. In contrast, other pseudosuchian groups dominated on land, occupied a wide range of ecological roles and exhibited a dizzying diversity of body shapes and sizes.

Despite their dominance, once the end-Triassic extinction hit, no non-crocodylomorph pseudosuchians survived. Whereas hyper-carnivore crocodylomorphs appeared to also die off, the terrestrial generalists made it through. The authors hypothesize that this ability to eat almost anything allowed them to survive, while so many other groups went extinct.

 

Read the full story by Lisa Potter in @The U.

2025 College of Science Awards

 

2025 College of Science AWARDS


The College of Science is committed to recognizing excellence in education, research and service.
Congratulations to all our 2025 College of Science award recipients!

 

Student Recognition

Research Scholar
Autumn Hartley
BS, Geology & Geophysics

Outstanding Undergraduate Student
Alice Parker, BS, Chemistry & Mathematics

Outstanding Graduate Student
Samantha Linn, Mathematics

Faculty Recognition

Excellence in Research
William Johnson, Professor, Geology & Geophysics

Excellence in Teaching and Mentoring
Peter Lippert, Associate Professor, Geology & Geophysics

Distinguished Educator
Ryan Stolley, Associate Director, Science Research Initiative

Distinguished Service
Sivaraman Guruswamy, Professor, Materials Science and Engineering


Postdoc Recognition

Outstanding Postdoctoral Researcher
Dustin Harper, Geology & Geophysics

Staff Recognition

Staff Excellence Award
Gordon Kafton, Systems Administrator, College of Mines and Earth Sciences


Safety Recognition

Excellence in Safety
David Carrier, Professor, School of Biological Sciences


Outstanding Undergraduate Research Award

Outstanding Undergraduate Researcher
Corrine Orton, Mathematics


Outstanding Undergraduate Research Mentor Award


Office for Undergraduate Research Mentor Award
Fred Adler, Professor, School of Biological Sciences


Office for Undergraduate Research Mentor Award
Martin Horvath, Associate Professor, School of Biological Sciences

 

For the College's 2024 Awards, click here.

 


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In Detox: Woodrats use ‘quantity over quality’ as a plan

Woodrats use ‘quantity over quality’ as a Detox plan


January 9, 2025
Above: A woodrat (N. lepida) between two food staples; juniper (left, ancestral diet) and creosote bush (right, new diet for the species).

Woodrats are one of the only animals that can tolerate large quantities of creosote, a shrub with leaves coated in a chemical cocktail of poisonous resin.

Part of the team doing field work in California to capture wild woodrats.

The critter’s constitution has astounded biologists and represents a decades-long debate—over evolutionary time, how do animals adapt to a deadly diet? Do detoxification enzymes become more specialized or more abundant?

The study, led by University of Utah (U) biologists, is the first to pinpoint the specific genes and enzymes that allow woodrats to eat the near-lethal food without obvious harm. The scientists compared the detoxification pathways of two woodrat species that encountered creosote independently in their evolutionary histories to those who had never encountered creosote. Before creosote invaded parts of the Southwest, woodrat populations had a smaller number of genes that coded for enzymes that process creosote toxins. As creosote grew to dominate the landscape, natural selection drove a detox-gene duplication bonanza, resulting in massive increases in the numbers of genes that produce enzymes that eliminate creosote toxins. Curiously, these enzymes did not become more specialized to detoxify creosote—there was just much more of them.

The authors propose that gene duplication is an important mechanism by which animals initially adapt to new environmental pressures.

“These woodrats have only been exposed to creosote bush for about 15,000 years—in an evolutionary timescale, that’s very little time,” said Dylan Klure, postdoctoral researcher at the U and lead author of the study. “Some other changes may happen in the future, but right now, the duplication innovation is what’s allowed them to become so toxin-resistant so quickly.”

The study published on Jan. 10, 2025, in the journal Science.

There are two primary hypotheses for how animals evolve tolerance to toxic chemicals. The first is that new DNA mutations modify existing detoxification enzymes to metabolize toxins faster and more efficiently—a lower quantity, higher quality approach. The second is that detoxification genes and the enzymes they produce don’t change much, but duplicate in number over evolutionary time, allowing animals to produce more detoxification enzymes in response to toxin consumption—a greater quantity, lower quality approach. Previous research found that herbivorous insects process toxins using specialized enzymes that metabolize chemicals faster. Since the 1970s, biologists have favored this “enzyme quality over quantity” hypothesis. This study found the exact opposite.

“We discovered that creosote-feeding woodrats don’t have specialized enzymes to metabolize creosote toxins, just more—many more, and from a wide variety of existing detox enzymes,” said Denise Dearing, U biologist and senior author of the study. “These duplications of existing genes increase the quantity of detoxification enzymes produced, enabling more toxin to be eliminated.”

Read the full article by Lisa Potter in @TheU 
Read the story as featured on NSF Stories.

Coyote numbers are often higher in areas where they are hunted

Coyote numbers are often higher in areas where they are hunted


January 9, 2025
Above: Trap camera photo of a coyote recorded in the Wasatch Mountains in October 2019. Credit: Austin Green.

Counterintuitive findings are based on images from hundreds of trap cameras deployed in nationwide campaign to document wildlife.

Coyote populations across the United States are influenced by a number of factors, but surprisingly their abundance is found to be higher in areas that allow hunting of the predator, according to research by a University of Utah wildlife biologist and colleagues in other states.

As U.S. landscapes became increasingly plowed and paved over the past couple centuries, wildlife has become less abundant thanks to the loss and fragmentation of habitat. But not coyotes, North America’s most successful mid-sized predator, which have expanded their range despite eradication campaigns and rapid urbanization.

Coyotes are bold generalists, eating anything from seeds, trash, roadkill, rodents, deer fawn, even pets, and fill niches left vacant by the elimination of bears, wolves and cougars, according to co-author Austin Green, a researcher with the U’s Science Research Initiative and former graduate student in the School of Biological Sciences.

It is reasonable to expect hunting to reduce species abundance, especially in conjunction with other anthropogenic factors that spurred the wave of Holocene extinctions. Unregulated hunting, after all, resulted in the disappearance of the passenger pigeon, dodo and monk seal, and near-extinctions of many other now-rare species, including iconic megafauna such as the American bison and white rhinoceros.

Coyotes, on the other hand, have displayed a pronounced resiliency in regions, such as Utah where hunting and trapping these predators is heavily subsidized and barely regulated, according to the findings based on extensive camera surveys.

“This is corroborating a lot of other evidence that direct hunting and intervention is actually not a really good way to manage coyote populations, if the goal is to decrease their abundance,” Green said.

The new study, which was funded in part by the U’s Global Change and Sustainability Center, was led by the University of New Hampshire (UNH). It relied on data compiled by Snapshot USA, a sprawling collaborative campaign to sample wild mammal populations with motion-triggered trap cameras arrayed in transects each fall.

Read the full article by Ethan Hood in @TheU 

The Next Antibiotic Revolution: Viruses to the Rescue

The Next Antibiotic Revolution: Viruses to the Rescue


Dec 09, 2024
Above: Talia Backman – Ph.D. student, School of Biological Sciences, shares a micrograph of tailocins.

From multicellular organisms, like us humans, to single-cell bacteria, living things are subject to attack by viruses. Plants, animals and even bacteria have evolved strategies to combat pathogens, including viruses that can threaten health and life.

Talia Backman, a University of Utah doctoral candidate wrapping up her final year in the School of Biological Sciences, found her project and niche in studying bacteria and the viruses that infect them.

She studies how bacteria create and use weapons, called “tailocins,” by repurposing genes from viruses.

“I’m especially interested in how bacteria have taken this a step further,” Backman said, “using remnants of past viral infections as a novel defense mechanism.”

“Phage” is the word that refers to the viruses that infect bacterial cells. While phages do not attack human cells, a lot can be learned from the strategies used by bacteria to survive a viral infection. Working with Talia Karasov, the principal investigator and assistant professor of biology (yes, they share the same first name), Backman recently helped make an unexpected discovery.

Repurposing viruses

“The bacterial strains (Pseudomonas) that I am studying are essentially repurposing the viruses that infect them,” Backman said, “retaining features from the infectious particles that ultimately help them to kill or co-exist with other strains of bacteria. These repurposed phage parts are called ‘tailocins.’ Understanding the role tailocins may be playing in shaping the prevalence, survival, and evolutionary success of certain bacterial strains is not well understood and is a major focus of the research in the Karasov lab.

Research on bacteria, and their unique viral pathogens, might just offer a novel solution to the antibiotic crisis. Beyond revealing how microbial communities combat infection, compete and evolve is the adjacent opportunity and potential to discover a new class of antibiotics.

Read the full article in @School of Biological Sciences.

2024 Clarivate’s Most Cited

Bill Anderegg, Highly Cited Researcher 2024


December 9, 2024
Above: William Anderegg at the One-U Responsible AI inaugural symposium in September. Courtesy of @The U.

Highly Cited Researchers have demonstrated significant and broad influence in their field(s) of research.

William Anderegg, associate professor in the School of Biological Sciences and director of the Wilkes Center for Climate Science and Policy has again been selected as one of Clarivate's Highly Cited Researchers for 2024. Each researcher selected has authored multiple Highly Cited Papers™ which rank in the top 1% by citations for their field(s) and publication year in the Web of Science™ over the past decade.

Citation activity, however, is not the sole selection indicator. This list, based on citation activity is then refined using qualitative analysis and expert judgment as the global analytics company observes for evidence of community-wide recognition from an international and wide-ranging network of citing authors.

Of the world’s population of scientists and social scientists, Highly Cited Researchers are 1 in 1,000.

“As the need for high-quality data from rigorously selected sources is becoming ever more important,"  says David Pendlebury, Head of Research Analysis at the Institute for Scientific Information at Clarivate, "we have adapted and responded to technological advances and shifts in the publishing landscape. Just as we have applied stringent standards and transparent selection criteria to identify trusted journals in the Web of Science™, we continue to refine our evaluation and selection policies for our annual Highly Cited Researchers™ program to address the challenges of an increasingly complex and polluted scholarly record.”

According to the Clarivate's website, "The Highly Cited Researchers 2024 list identifies and celebrates individuals who have demonstrated significant and broad influence in their fields of research. Through rigorous selection criteria and comprehensive analysis, we recognize researchers whose exceptional and community-wide contributions shape the future of science, technology and academia globally."

"This program also emphasizes our commitment to research integrity. Our evaluation and selection process continues to evolve with filters to address hyper-authorship, excessive self-citation, anomalous citation patterns and more, ensuring that recognized researchers meet the benchmarks we require for this program."

Exploring the "global landscape of top-tier research talent," they continue, "provides us with insights on global research and innovation trends."

This year Clarivate™ awarded 6,886 Highly Cited Researcher designations to 6,636 individuals. Some researchers have been recognized in more than one Essential Science Indicators™ (ESI) field, resulting in more designations than individual awardees. This analysis, which includes the distribution of designations across nations and institutions, reflects the impact of these 6,886 appearances, distributed across fields, in accordance with the size of each.

While the sole researcher from the College of Science this year to be honored with the designation, Anderegg, one of three at the University of Utah, was the only one at the U to appear in two categories, Plant & Animal Science and Environment & Ecology.

This table summarizes the number of researcher designations by field of research and the cross-field category.

One-U Responsible AI

William-Anderegg

Anderegg is also the executive committee member who leads the One-U Responsible AI’s environmental working group. The group’s members bring their diverse expertise to establish ethical policy, explore AI’s impact on society and the environment, and develop responsible methods for using AI to improve climate research.

“Our goal of this working group is to put together a vision and a mission about responsibly developing and using AI to address human environmental challenges across scales to promote resilience and foster sustainable development,” said Anderegg at the group's inaugural symposium this past September. “AI could have an enormous negative impact on the environment itself. There are direct impacts for the cost of running AI—the power and water needed to run the massive data centers, and the greenhouse gas emissions that result. Then there are indirect challenges—misinformation, polarization, and increasing demands on the power grid. At the same time, there are another set of opportunities in using AI to tackle the marginal problems in forecasting and grid rewarding systems.”

The working group’s vision is to utilize AI to bolster our resilience to climate change with collaboration, training, technology, and ethical governance.

“The University of Utah is set to engage in these two focal areas of developing sustainable AI—how we use AI in a manner that minimizes environmental impact and maximizes long-term sustainability? Then, how do we harness AI for environmental resilience challenges?” Anderegg noted.

This is the second year in a row that Anderegg has made the Highly Cited Researcher list. With his mentor, biology professor emeritus John Sperry, the two were honored in the 2023 cohort. The two of them worked closely together, publishing multiple papers over the course of about six years in the areas of plant hydrology and forest stress. Their research is an auspicious example of how, in the tradition of peer-reviewed research, scientists routinely stand on the shoulders of others to move forward human understanding.

You can link to selected publications by Bill Anderegg here


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New tools for peering into cell function.

New tools for peering into cell function


Sep 9, 2024
Above: Ming Hammond, professor of chemistry. PHOTO CREDIT: Dave Titensor, University of Utah

U chemists discover how key contrast agent works, paving the way to create markers needed for correlative microscopy.

Two labs at the University of Utah’s Department of Chemistry joined forces to improve imaging tools that may soon enable scientists to better observe signaling in functioning cells and other molecular-scale processes central to life.

Rodrigo Noriega, assistant professor of chemistry and co-author of the study.

The Noriega and Hammond labs, with complementary expertise in materials chemistry and chemical biology, made critical discoveries announced this month in the Journal of the American Chemical Society that could advance this goal. Their joint project was kickstarted through a team development grant from the U College of Science and the 3i Initiative to encourage faculty with different research interests to work together on big-picture problems.

“We’re trying to develop a new kind of imaging method, a way to look into cells and be able to see both their structural features, which are really intricate, while also capturing information about their activity,” said co-author Ming Hammond, a professor of chemistry. "Current methods provide high-resolution details on cellular structure but have a challenging ‘blind spot’ when it comes to function. In this paper, we study a tool that might be applied in electron microscopy to report on structure and function at the same time.”

Biological samples often need “markers,” or molecules that are the source of detectable signals, explained co-author Rodrigo Noriega, an assistant professor of chemistry. A widely used type of markers are flavoproteins which, when photoexcited, trigger a chemical reaction that yields metal-absorbing polymer particles whose high contrast in electron microscopy is easily seen.

Scientists had long assumed that a mechanism involving singlet oxygen generation, a special kind of reactive oxygen species, was at play. However, the U team found that electron transfer between the photoexcited marker and the polymer building blocks is the main contributor to the process.

You can read the full story by Brian Maffly in @TheU.

 

Scientists Find Hope in Cone Snail Venom

Scientists Find Hope in Cone Snail Venom


Aug 23, 2024
Above : Ho Yan Yeung, PhD (left) and Thomas Koch, PhD (right, also an author on the study) examine a freshly-collected batch of cone snails. Image credit: Safavi Lab.

Based on work by Toto Olivera, the father of research on cone snail venom, scientists are now finding clues for how to treat diabetes and hormone disorders in a toxin from one of the most venomous animals on the planet.

An international research team led by University of Utah scientists has identified a component within the venom of a predatory marine cone snail, the geography cone, that mimics a human hormone called somatostatin, which regulates the levels of blood sugar and various hormones in the body. The hormone-like toxin’s specific, long-lasting effects, which help the snail hunt its prey, could also help scientists design better drugs for people with diabetes or hormone disorders, conditions that can be serious and sometimes fatal.

The results were published Aug. 20 in the journal Nature Communications.

A blueprint for better drugs

Somatostatin acts like a brake pedal for many processes in the human body, preventing the levels of blood sugar, various hormones, and many other important molecules from rising dangerously high. The cone snail toxin, called consomatin, works similarly, the researchers found—but consomatin is more stable and specific than the human hormone, which makes it a promising blueprint for drug design.

By measuring how consomatin interacts with somatostatin’s targets in human cells in a dish, the researchers found that consomatin interacts with one of the same proteins that somatostatin does. But while somatostatin directly interacts with several proteins, consomatin only interacts with one. This fine-tuned targeting means that the cone snail toxin affects hormone levels and blood sugar levels but not the levels of many other molecules.

In fact, the cone snail toxin is more precisely targeted than the most specific synthetic drugs designed to regulate hormone levels, such as drugs that regulate growth hormone. Such drugs are an important therapy for people whose bodies overproduce growth hormones. Consomatin’s effects on blood sugar could make it dangerous to use as a therapeutic, but by studying its structure, researchers could start to design drugs for endocrine disorders that have fewer side effects.

Consomatin is more specific than top-of-the-line synthetic drugs—and it also lasts far longer in the body than the human hormone, thanks to the inclusion of an unusual amino acid that makes it difficult to break down. This is a useful feature for pharmaceutical researchers looking for ways to make drugs that will have long-lasting benefits.

Learning from cone snails

Finding better drugs by studying deadly venoms may seem unintuitive, but Helena Safavi, associate professor of biochemistry in the U’s Spencer Fox Eccles School of Medicine and the senior author on the study, explained that the toxins’ lethality is often aided by pinpoint targeting of specific molecules in the victim’s body. That same precision can be extraordinarily useful when treating disease.

“Venomous animals have, through evolution, fine-tuned venom components to hit a particular target in the prey and disrupt it,” Safavi said. “If you take one individual component out of the venom mixture and look at how it disrupts normal physiology, that pathway is often really relevant in disease.” For medicinal chemists, “it’s a bit of a shortcut.”

Among Safavi’s coauthors are faculty from the U’s School of Biological Sciences, including Baldomero Olivera and Samuel Espino. The U has been a hotspot for research into the venom’s pharmacological properties since Olivera arrived in Utah in 1970 from his native Philippines, bringing his interest in cone snails with him.

Read the full, original story by Sophia Friesen in UofU Health.
Read about Toto Olivera’s 2022 Golden Goose Award for early research in cone snails here.

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?

Fred Alder. Credit: Mathew Crawley

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

 

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. 

The dynamics of escape in a person with imperfect initial control.  We see replacement by increasingly dark shades of gray that indicate cells that are growing faster and faster, leading to an increase in the total cell population (black line at top) above the healthy level (horizontal orange line).

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 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