bio-news

Visualizing the Infinitesimal

September 29, 2022

Visualizing the Infinitesimal

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

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

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

Vol 324, Issue 5935

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

For Ofer Rog, Assistant Professor and Mario Capecchi Chair in the School of Biological Sciences, this revelation completely revised the interpretation of his experiments, but also brought with it “whole sets of biological issues.” The existence of crowding in the cell was one of them. No longer could he try to reduce the behavior of the chromosomes he was studying to properties of single molecules that make them up. “Rather,” says Rog, “we had to understand them as collective or ‘emergent’ behavior.”

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

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

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

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

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

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

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

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

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

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

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

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

The Workshop
Which leads us to the Re-Imagining a Cellular Space Occupied by Condensates symposium and workshop, borne out of the ready collaboration between Rog and Iwasa. While the Animation Lab’s initial foray into condensates was, in the beginning, educationally focused, that somewhat limited approach may now be at an inflection point.

“When Ofer and I talked,” says Iwasa, “we agreed that the research community had not yet reached any sort of consensus on how best to represent condensates. So our attempts to capture condensates by animation didn’t have a visual language to fall back on.”

Greater consensus may emerge at the symposium & workshop on October 11-13. Unlike the many traditional meetings dedicated to condensates, where scientists present and debate the minute details of their experiments, here scientists will interact with illustrators and other “tool builders,” to discuss the visual language of condensates.

While there is always a risk in illustration (including digital animation) of simplifying things too much and thus restricting future perceptions and scientific understanding, the symposium also pre-supposes that the conversation is essential. In short, the gathering promises to “daylight” how biologists represent a subcellular world in enabling as well as disabling ways, seeking “to build a community that will construct a visual language and new tools that will accurately capture the complexity of molecular condensates.” These representations will help generate experimentally-testable hypotheses, and will lead to the development of new techniques for scientific communication and teaching.

“One of the things that we realized,” says Rog, “is that challenges similar to the one we are facing now, in the condensate field, must have been figured out by other fields in the past, in biology and outside biology.” Symposium participants will include experts from diverse disciplines: about one-third of the participants are biologists, actively engaged in condensate research; one-third will be visualization and computation specialists—like watercolorist David Goodsell mentioned above—but also modeling experts, data visualization specialists, and molecular animators.

The final one-third will come from fields that are not commonly engaged with molecular biology but that have long been thinking about space and ways to represent it. This last group includes software and virtual reality developers and academics in architecture and history.

The symposium will take place at the Crocker Science Center at the University of Utah, on October 11, 2022, 9 AM to 5 PM, and is open to the public. It will be followed by a two-day workshop (by invitation only).

 

By David Pace. First published @ biology.utah.edu

 

>> HOME <<

 

Golden Goose 2022

September 20, 2022

Golden Goose Award

Baldomero "Toto" Olivera

A side hustle that transformed neuroscience.

As scientists working in the Philippines in the 1970s, biochemists Baldomero Olivera and Lourdes Cruz, professor emeritus of the University of the Philippines Diliman, found it tough to get hold of the right supplies for DNA research.

“We had to find something to do that didn’t require fancy equipment because we had none,” said Olivera, a distinguished professor at The University of Utah’s School of Biological Sciences, in a video produced for the Golden Goose awards.

Olivera and Cruz came up with what they hoped would be a fruitful side project. Cone snails are commonplace in the Philippines, and they had always fascinated Olivera, who had collected shells as a child. The pair decided to research the nature of the venom that the snails used to paralyze their tiny fish prey.

Cone Snail Shells

The team discovered the bioactive compounds in the venom were tiny proteins known as peptides. After moving to the US and teaming up with University of Utah grad students Dr. Michael McIntosh and the late Craig T. Clark, Olivera and Cruz learned that some of the venom peptides reacted differently in mice than in fish and frogs. It turned out in mammals the compounds were involved in the sensation of pain, rather than muscle paralysis.

“There was this incredible gold mine of compounds,” said McIntosh in the video. He is now a professor and director of research of psychiatry in the School of Biological Sciences at The University of Utah.

On September 14, 2022, the American Association for the Advancement of Science (AAAS), the world’s largest multidisciplinary scientific society, hosted the 11th annual Golden Goose Award ceremony, a celebration of federally funded research that unexpectedly benefits society. AAAS awarded University of Utah research of a non-opioid pain reliever, hidden in the venom of tiny cone snails, which greatly decreases pain for patients with chronic illnesses while helping scientists develop new ways to map the body’s nervous system. As undergraduate researchers, Craig Clark (in memoriam) and J. Michael McIntosh, now a professor of psychiatry at the U, isolated a compound that eventually led to an approved non-opioid pain killer. Baldomero M. Olivera, Distinguished Professor in the School of Biological Sciences, and Lourdes J. Cruz, then faculty of biology at the U and now Professor Emeritus at the University of the Philippines, supervised the research. The award recognizes all four individuals.

The Golden Goose Award spotlights scientific research that may have appeared obscure, sounded funny, or for which the results were unforeseen at the outset but ultimately, and often serendipitously, led to breakthroughs. This year, the award comes on the heels of the U.S. Congress passing and President Biden signing the bipartisan and historic CHIPS and Science Act. This new law reauthorizes key federal agencies whose projects will propel discovery, build on our strengths, and show what American investment, intellect, ingenuity and risk-taking can accomplish — precisely the type of innovation the Golden Goose Award honors.

U.S. Representative Jim Cooper (D-TN), often referred to as “Father Goose,” will retire from Congress at the end of this term. He conceived of the award as a strong counterpoint to criticisms of basic research as wasteful federal spending, such as the late Sen. William Proxmire’s (D-WI) Golden Fleece Award, leading to a coalition of business, university, and scientific organizations establishing the award in 2012. Thanks to his legacy, the award will continue to elevate the importance of recognizing basic science that ultimately improves people’s quality of life.

“The Golden Goose Award reminds us that potential discoveries could be hidden in every corner and illustrates the benefits of investing in basic research to propel innovation,” said Sudip S. Parikh, chief executive officer at AAAS and executive publisher of the Science family of journals. “AAAS is honored to elevate this important work since the award’s inception, and we thank Representative Cooper for his tireless leadership and dedicated support to this award and the scientific community.”

Tiny snail, big impact
In the 1970s, Olivera and collaborator Cruz were interested in the deadly venom used by cone snails, marine creatures native to the Philippines. When Olivera moved to the U, his focus shifted to other areas, but he kept the cone snail venom as a side project. In 1979 he assigned two undergraduate researchers the task of isolating the venom’s components and testing their impacts on mice. Craig Clark, a sophomore biology major, and McIntosh, a 19-year-old who just graduated high school, discovered something unexpected—a compound they named “shaker peptide” blocked calcium channels in the mice, which are the nerve’s ability to communicate with the rest of the body. Later, they found that the shaker peptide specifically targeted the channels related to pain in mammals and is 1,000 times as powerful as morphine. McIntosh is now a professor of psychiatry at the U with his own lab and thirty years later, continues to work with Olivera to explore the therapeutic potential of cone snail venom that has one of the most promising non-opioid alternatives to manage pain. One compound become an FDA-approved painkiller.

2022 Golden Goose Awards Ceremony

The student project of Clark and McIntosh is part of a long tradition of undergraduate research in the U’s College of Science. Fifty years ago, K. Gordon Lark, the first chair of the Department of Biology at the U, started an initiative to support undergrad research opportunities in faculty laboratories, an initiative that led to recruiting biology undergraduates such as Clark and McIntosh. The College of Science is expanding his legacy under a newly created Science Research Initiative, which provides most U science undergraduates with a unique opportunity to pursue their own independent research projects.

2022 Golden Goose Awardees:

Craig T. Clark (in memoriam), Lourdes J. Cruz (University of the Philippines), J. Michael McIntosh (University of Utah; George E. Wahlen VA Medical Center), and Baldomero Marquez Olivera (University of Utah)
Tiny Snail, Big Impact: Cone Snail Venom Eases Pain and Injects New Energy into Neuroscience
Impeded by supply chain issues while conducting DNA research in the Philippines, Lourdes Cruz and Baldomero Olivera began examining cone snails, a group of highly venomous sea mollusks which happened to be in abundant supply along the country’s coastal waters. Several decades and countless airline miles later, and with the help of then-undergraduate students Craig Clark and Michael McIntosh, the team discovered the raw material for a non-opioid pain reliever and a powerful new tool for studying the central nervous system, all hidden in the cone snail’s potent venom

Ron Kurtz (RxSight), Tibor Juhasz (ViaLase), Detao Du (Rayz Technologies), Gerard Mourou (Ecole Polytechnique), and Donna Strickland (University of Waterloo)
How a Lab Incident Led to Better Eye Surgery for Millions of People
Nearly 30 years ago, a graduate student at the University of Michigan’s Center for Ultrafast Optical Science (CUOS) experienced an accidental laser injury to his eye. Fortunately, his vision was not severely affected. However, the observation of the very precise and perfectly circular damage produced by the laser led to a collaboration. Eight years later, that group of researchers developed of a bladeless approach to corrective eye surgery. The new procedure, also known as bladeless LASIK, uses a femtosecond laser rather than a precision scalpel cut into the human cornea before it is reshaped to improve the patient’s vision.

Manu Prakash (Stanford University) and Jim Cybulski (Foldscope Instruments Inc.)
Foldscopes and Frugal Science: Paper Microscopes Make Science Accessible
While researching in remote areas of India and Thailand, a technical challenge piqued Manu Prakash’s curiosity. In certain areas of the world, transport, training, and maintenance barriers can make state-of-the-art microscopes inaccessible. Prakash found a potential solution in a decidedly un-technical material: paper. Using principles of origami applied to printer paper, matchboxes, and file folders, Prakash and graduate student Jim Cybulski designed a paper microscope known as the Foldscope that can achieve powerful magnification with materials that cost less than $1 to manufacture. Today, just over a decade later, two million Foldscopes have been distributed in over 160 countries and have been used to diagnose infectious diseases, diagnose new species, and identify fake drugs, among many other applications.

 

first published @ CNN and @theU

>> HOME <<

At-Risk Forests

September 7, 2022

At-Risk Forests

Global analysis identifies at-risk forests.

Forests are engaged in a delicate, deadly dance with climate change, hosting abundant biodiversity and sucking carbon dioxide out of the air with billions of leafy straws. They can be a part of the climate solution as long as global warming, with its droughts, wildfires and ecosystem shifts, doesn’t kill them first.

In a study published in Science, William Anderegg, the inaugural director of the University of Utah’s Wilkes Center for Climate Science and Policy, and colleagues quantify the risk to forests from climate change along three dimensions: carbon storage, biodiversity and forest loss from disturbance, such as fire or drought. The results show forests in some regions experiencing clear and consistent risks. In other regions, the risk profile is less clear, because different approaches that account for disparate aspects of climate risk yield diverging answers.

 

William Anderegg

“Large uncertainty in most regions highlights that there's a lot more scientific study that's urgently needed.”

 

An international team

Anderegg assembled a team including researchers from the United Kingdom, Germany, Portugal and Sweden.

“I had met some of these folks before,” he says, “and had read many of their papers. In undertaking a large, synthetic analysis like this, I contacted them to ask if they wanted to be involved in a global analysis and provide their expertise and data.”

Their task was formidable –assess climate risks to the world’s forests, which span continents and climes and host tremendous biodiversity while storing an immense amount of carbon. Researchers had previously attempted to quantify risks to forests using vegetation models, relationships between climate and forest attributes and climate effects on forest loss.

“These approaches have different inherent strengths and weaknesses,” the team writes, “but a synthesis of approaches at a global scale is lacking.” Each of the previous approaches investigated one dimension of climate risk: carbon storage, biodiversity, and risk of forest loss. For their new analysis, the team went after all three.

Three dimensions of risk

“These dimensions of risk are all important and, in many cases, complementary. They capture different aspects of forests resilience or vulnerability,” Anderegg says.

  • Carbon storage: Forests absorb about a quarter of the carbon dioxide that’s emitted into the atmosphere, so they play a critically important role in buffering the planet from the effects of rising atmospheric carbon dioxide. The team leveraged output from dozens of different climate models and vegetation models simulating how different plant and tree types respond to different climates. They then compared the recent past climate (1995-2014) with the end of the 21st century (2081-2100) in scenarios of both high and low carbon emissions. On average, the models showed global gains in carbon storage by the end of the century, although with large disagreements and uncertainty across the different climate-vegetation models. But zooming in to regional forests and taking into account models that forecast carbon loss and changes in vegetation, the researchers found higher risk of carbon loss in southern boreal (just south of the Arctic) forests and the drier regions of the Amazon and African tropics.
  • Biodiversity: Unsurprisingly, the researchers found that the highest risk of ecosystems shifting from one “life zone” to another due to climate change could be found at the current boundaries of biomes – at the current transition between temperate and boreal forests, for example. The models the researchers worked from described changes in ecosystems as a whole and not species individually, but the results suggested that forests of the boreal regions and western North America faced the greatest risk of biodiversity loss.
  • Disturbance: Finally, the authors looked at the risk of “stand-replacing disturbances,” or events like drought, fire or insect damage that could wipe out swaths of forest. Using satellite data and observations of stand-replacing disturbances between 2002 and 2014, the researchers then forecast into the future using projected future temperatures and precipitation to see how much more frequent these events might become. The boreal forests, again, face high risk under these conditions, as well as the tropics.

“Forests store an immense amount of carbon and slow the pace of climate change,” Anderegg says. “They harbor the vast majority of Earth's biodiversity. And they can be quite vulnerable to disturbances like severe fire or drought. Thus, it's important to consider each of these aspects and dimensions when thinking about the future of Earth's forests in a rapidly changing climate.”

Future needs

Anderegg was surprised that the spatial patterns of high risk didn’t overlap more across the different dimensions.

“They capture different aspects of forests' responses,” he says, “so they wouldn't likely be identical, but I did expect some similar patterns and correlations.”

Models can only be as good as the basis of scientific understanding and data on which they’re built and this study, the researchers write, exposes significant understanding and data gaps that may contribute to the inconsistent results. Global models of biodiversity, for example, don’t incorporate dynamics of growth and mortality or include the effects of rising CO2 directly on species. And models of forest disturbance don’t include regrowth or species turnover.

“If forests are tapped to play an important role in climate mitigation,” the authors write, “an enormous scientific effort is needed to better shed light on when and where forests will be resilient to climate change in the 21st century.”

Key next steps, Anderegg says, are improving models of forest disturbance, studying the resilience of forests after disturbance, and improving large-scale ecosystem models.

The recently-launched Wilkes Center for Climate Science and Policy at the University of Utah aims to provide cutting-edge science and tools for decision-makers in the US and across the globe. For this study, the authors built a visualization tool of the results for stakeholders and decision-makers.

Despite uncertainty in the results, western North America seems to have a consistently high risk to forests. Preserving these forests, he says, requires action.

“First we have to realize that the quicker we tackle climate change, the lower the risks in the West will be,” Anderegg says. “Second, we can start to plan for increasing risk and manage forests to reduce risk, like fires.”

Find the full study here.

 

by Paul Gabrielsen, first published in @theU.

College Rankings

September 1, 2022

College Rankings

U.S. News & World Report has released their 2022-2022 National University Rankings. The University of Utah is now ranked No. 1 in Utah and No. 42 nationally among public universities.

The College of Science fared even better. National rankings for public universities put Biology at No. 13, Chemistry at No. 20, Mathematics at No. 22, and Physics & Astronomy at No. 47.

There are many factors used to determine a school’s final ranking in the U.S. News & World Report but one factor that is not considered is cost. When cost is factored, there are few universities that challenge the University of Utah.

>> HOME <<

Crystal Su

August 24, 2022

Crystal Su

A new paper in Current Biology describes the development of a novel, synthetic insect-bacterial symbiosis.

The symbiotic bacteria express a red fluorescent protein that is visible through the insect cuticle, facilitating characterization of the mechanics of infection and transmission in insect tissues and cells. In addition, Su et al. engineered the bacteria to modify their ability to synthesize aromatic amino acids, which are used by the insect host to fuel cuticle strengthening. Correspondingly, insects maintaining bacteria that overproduce these nutrients exhibited stronger cuticles, signifying mutualistic function. The establishment of this synthetic symbiosis will facilitate detailed molecular genetic analysis of symbiotic interactions and presents a foundation for the use of genetically-modified symbionts in the engineering of insects that transmit diseases of medical and agricultural importance. The paper is titled “Rational engineering of a synthetic insect-bacterial mutualism.”

Red fluorescent proteins in a weevil.

Broader context
SBS Professor and Principal Investigator Colin Dale says, “the work described in the paper was catalyzed and conducted by Crystal Su, an extremely brave and dedicated graduate student in SBS, who took on this very high risk and transformative project and pushed through numerous roadblocks, doggedly refusing to take no for an answer.” Su engaged three additional labs–Golic, Rog and Gagnon–in SBS to assist with specialist techniques, highlighting the utility of interdisciplinary science and the breadth of talent and collaborative spirit that exists in SBS.

Dale views Su’s work as a “bucket list” accomplishment, “something I dreamed about while playing cricket games at Bristol University Vet School during my Ph.D. While Crystal dedicated six years of her life to bring this novel new biology to life, it’s also the product of foundational work by SBS graduate students in the decade prior, involving the identification, characterization, culture and development of genetic tools for proto-symbionts free-living bacteria that have the capability to establish stable, maternally-transmitted associations with insects.”

Synthetic Biology
Synthetic Biology focuses on utilizing engineering approaches to design and fabricate organisms (including associations and communities) that do not exist in the natural world. It can yield practical solutions for a wide range of problems in medicine, agriculture, materials and environmental sciences. In addition, it can be used to investigate the functions of natural systems, via replication and manipulation, as highlighted in the Su et al. paper. To understand its potential, it is useful to think of the contribution of synthetic approaches to other disciplines in science, most notably in chemistry, says Dale who also serves in the School of Biological Sciences as Section Head, Genetics and Evolution.

 

Read the paper in Current Biology
Read the article on Undergraduate Research in the Dale Lab

 

by David Pace, first published @biology.utah.edu

>> HOME <<

Ants of the World

August 15, 2022

Ants of the World

Seeing the world through ants.

Known affectionately as “Ant Man” in the School of Biological Sciences at the University of Utah and beyond, John “Jack” Longino is part of a globe-spanning initiative called the Ants of the World Project that aims to generate the most complete phylogenetic tree of the ant family (Formicidae) to date.

Part of that project is Ant Course, a regularly-occurring field course on ant biology and identification. After three years of accommodating the pandemic, this year the group, involving multiple research universities, is convening in Vietnam August 1-13. During the course, the world’s ant identification experts get together to teach 24 students all about ants. Beginning in 2001, the course has been staged in the United States, Costa Rica, Venezuela, French Guiana, Peru, Uganda, Mozambique, Borneo, and Australia.

“These courses have become famous,” says Longino, “with generations of students being shaped and connected by their Ant Course experience.” The Ants of the World project, he explains, integrates teaching and research. The initiative funds three new Ant Courses in locations that are poorly known, training new generations of ant biologists while they learn about the ants of these regions.

 

John “Jack” Longino

"These courses have become famous," says Longino, "with generations of students being shaped and connected by their Ant Course experience."

 

“After a long delay due to COVID, we are finally offering our first Ant Course, in Vietnam,” says Longino of their field site in Cúc Phương National Park, just south of Hanoi. “I’m really looking forward to meeting this new group of students, interacting with Asian colleagues, and experiencing first-hand the ant fauna of Southeast Asia.” Situated in the foothills of the northern Annamite Range, the national park consists of verdant karst mountains and lush valleys with an elevation that varies from 150 meters (500 feet) to 656 m (2,152 feet) at the summit of May Bac Mountain, or Silver Cloud Mountain.

It’s all part of Ants of the World Project’s attempt to survey nearly all ant genera and just under half the described species using advanced genome reduction techniques. The result will be a comprehensive evolutionary tree of ants, out to the smallest branch tips.

The resulting data set will help researchers answer questions: Are there predictable patterns of intercontinental dispersal and diversification? Following dispersal to a new region, is there accelerated filling of morphological and climate space? How have biotas responded to climate shifts in the past? Can we predict how ants will respond to current rapid climate change?

Eurhopalothrix semicapillum, named for the hairy patches on its face.

Longino and Elaine Tan, a graduate student in the Longino lab, will be meeting up with 34 other ant specialists and ant specialists-to-be. Along with “Ant Man,” course faculty include the other principal investigators of the Ants of the World Project: Michael Branstetter (USDA-ARS), Bonnie Blaimer (Museum für Naturkunde in Berlin, Germany), Brian Fisher (California Academy of Sciences) and Philip Ward (UC Davis).

Ants of the World is a collaboration of four different institutions, including the School of Biological Sciences. Ant Course is organized and run by the California Academy of Science and is designed for scholars to share information and discover together the ants of a particular region. It applies ant biology to established areas of inquiry but also encourages students to ask new questions.

Zahra Saifee is a University of Utah intern who will be accompanying the team as a scientific communications specialist. She says of Ant Course, “it really is about the ants, what new species there are in [a particular region and] where species overlap. The team discusses their observations of what they’re doing with others across the world. The core is bringing diverse people to ‘nerd out’ about it for two weeks.”

A lot of the time in Vietnam, says Saifee, is set up just to explore and see what people will find. “Curiosity is at a premium, bringing observations to the group as a sounding board. People can bring to the group ‘rough drafts’ of research and ideas.”

This open-door approach to discovery was transformative for Rodolfo Probst, PhD, a member of the Longino lab who successfully defended his dissertation just this month. His 2013 Ant Course experience in Borneo connected him to a year’s work back east following his graduation from college before he settled into graduate school as part of Longino’s lab.

Ants are the focus of that lab’s research but it’s not just about ants. The research goals of the Longino lab involve “reciprocal illumination,” in which the latest evolutionary concepts of species formation, combined with the latest genetic tools, allow the construction of a detailed “biodiversity map” of ants. The patterns revealed in the map then inform general concepts of biological diversification.

The research has the additional benefit of allowing other researchers, like those students participating in Ant Course, to more easily identify ants. To this end, Longino helps curate a large on-line specimen and image database (Antweb.org), a major resource for ant researchers worldwide.

To study the way ants network can potentially speak to the design and character of larger eco-systems, Saifee suggests, making the study of ants more than a niche science. It propels one to look at the larger picture of life—not just its wonders, but its changes and adaptations. In short, its ecology and evolution. “There are a lot of different species [of ants] and how we organize data is key to new scientific discoveries,” concludes Saifee.

Making new discoveries about ants is important because, as subject models, they are on par with vertebrates and vascular plants as key taxa for ecology, evolutionary biology, biogeography, conservation biology, and public interest. Having a solid phylogenetic history opens entire new worlds of biological exploration, and has been achieved for vertebrates and many plants. With a little more effort, much of which is being addressed by the NSF-funded Ants of the World project, the same can be true for ants.

Ant Course in Vietnam is currently at the center of that ambition. Follow the Ant Course blog and on Twitter @AntsProject. Read the profile of graduate student Elaine Tan, who is accompanying Jack Longino to Vietnam here.

 

First published at biology.utah.edu

 

N.S.F. Director

August 10, 2022

National Science Foundation

The National Science Foundation has announced a 2-to-4-year appointment of Denise Dearing as Director for the Division of Integrative Organismal Systems.

The Division of Integrative Organismal Systems (IOS) is one of four divisions within the Directorate of Biological Sciences at the NSF. The Division Director provides vision and leadership, and contributes to NSF’s mission by supporting fundamental research to advancing our understanding of organisms as integrated units of biological organization. The Division Director also provides guidance to program officers and administrative and support staff, and assesses needs and trends, develops breakthrough opportunities, implements overall strategic planning, and policy setting.

Both the NSF and the UU are supportive of Denise continuing to participate in her on-going research program and provide mechanisms and resources to enable the research in her group to continue and advance during her time at the NSF.

Dearing is Distinguished Professor in Biology at the University of Utah and a two-term former chair of the department which was made a School in 2018 after which she became director. The research in the Dearing lab focuses on understanding how small mammals overcome challenges related to diet and disease. “Our work draws on approaches from many disciplines (e.g., physiology, ecology, pharmacology, genetics, biochemistry, ethology) and combines field and laboratory studies,” says Dearing whose research website features three current projects: Understanding the genetic underpinnings that enable ingestion of poisonous diets; Investigating the role of gut microbes in facilitating the ingestion of dietary toxins; and Rules of Resilience: Modeling impacts of host-microbe interactions during perturbations.

Dearing earned her B.S. in Biology from Eastern Connecticut State University, 1985 an M.S. in Biology from the University of Vermont in 1988, and a Ph.D. in Biology from the University of Utah in 1995. She served as Associate Dean, College of Science between 2012 and 2014.

Among her awards and honors are the 2018 Joseph Grinnell Award (American Society of Mammalogist); the 2014 C. Hart Merriam Award (American Society of Mammalogists); a 2008 Graduate Student and Postdoctoral Scholar Distinguished Mentor Award; and a 2008 Distinguished University Teaching Award (University of Utah).

 

by David Pace, first published @biology.utah.edu

>> HOME <<

Cellular Crosslinking

July 19, 2022

Cellular Crosslinking

Structural signatures of Escherichia coli chemoreceptor signaling states revealed by cellular crosslinking

Motile bacteria are capable of swimming efficiently toward favorable chemical environments and away from inhospitable ones. This behavior–called “chemotaxis”–is frequently used by unicellular organisms for finding food.

Not surprisingly, such behaviors play important roles in establishing beneficial host symbioses and pathogenic infections. The value of understanding in detail this mechanism of directed cell migration in response to extracellular chemical signals cannot be over-stated, and Escherichia coli, commonly referred to as E. coli, has become the paradigm molecular model.

“Despite their tiny size, bacteria have evolved amazingly sophisticated protein machines for detecting and responding to changes in their environment,” says John “Sandy” Parkinson, principal investigator in the School of Biological Sciences. Caralyn Flack, a research associate in the Parkinson Lab, developed a technique for monitoring the behavior of living bacteria before and after she changed the structure of a critical signaling protein inside the cell.

Flack’s new findings were recently published in Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS). The paper, titled “Structural signatures of Escherichia coli chemoreceptor signaling states revealed by cellular crosslinking,” makes an important advance in elucidating the molecular mechanism(s) of signal propagation through chemoreceptor molecules.

Caralyn Flack

"This new cellular crosslinking approach delivers unprecedented insight into receptor structural properties as the receptors function within cells"

 

“Bacteria are amazing at sensing and responding quickly to changes in their environment,” states Flack. “This makes them a great model for trying to understand transmembrane signaling.” But it turns out that changes that accompany signaling events in chemoreceptors are difficult to follow with traditional structural methods, and those techniques that do work cannot replicate the native cellular environment. To remedy that, the technique Flack developed does three things. First, it assesses behavior. Second, it changes the structure of a protein inside living bacteria, and third, it then watches the signaling behavior change in real-time. The technique, which involves “crosslinking,” she says, has proven to be “really powerful for structure-function analyses of signaling proteins.”

In essence, what Flack did was create receptor proteins with a special amino acid at a position of interest. That amino acid, cysteine, has unique chemical properties that, under the right conditions, allow it to form a covalent bond (to “crosslink”) to a nearby cysteine in the same protein or in another protein. Such crosslinks constrain the structural movements of the proteins and can change its behavior. This is how Flack was able to change the structure, and in consequence, the function of a receptor within a living cell.

The crosslinking reporter sites “enabled us to evaluate receptor output states before and after crosslink formation,” she writes. This new cellular crosslinking approach “delivers unprecedented insight into receptor structural properties as the receptors function within cells” stated one reviewer of the PNAS manuscript. Flack suggests that “similar crosslinking approaches could serve to follow signal transmission in other regions of the chemoreceptor molecule and perhaps in other signaling proteins, as well.”

Work on those topics is ongoing.

Photo: Colorized scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip by NIAID on Flickr

 

by David Pace, first published in biology.utah.edu.

 

PAYTON UTZMAN

July 14, 2022

Payton Utzman

Many people wouldn’t see a direct line between working on John Deere tractors in rural Washington State and working on a DNA repair enzyme that functions to prevent cancer in humans.

But that’s the unlikely trajectory of Payton Utzman BS’22 who after graduating from the School of Biological Sciences headed off to join Nabla Bio at a 15,000-square-foot state-of-the-art wet laboratory and co-working space for high-potential biotech and life science ventures at Harvard University.

“We are a small team of nine scientists,” says Utzman, “working to synthesize therapeutic antibodies that are designed by artificial intelligence. It has been an amazing experience so far learning so many new skills and applying my undergraduate research experience in such a useful way.”

 

Payton Utzman BS'22

"The elegant and candid relationship between the structure of a protein and its corresponding function resembled my understanding of how metal parts assembled into an engine can produce incredible amounts of power."

 

Granted, it wasn’t a just a bounce from the spring seat of a John Deere tractor in Pullman, WA to Boston. But Utzman’s mechanically-oriented mind found a formidably gratifying corollary in biochemistry and structural biology in the Horvath lab. “I spent my childhood weekends helping my father and grandfather maintain various tractors and machinery. By the time I graduated high school, I was a self-taught mechanic, having restored an old pickup and rebuilding the engine through the guidance of a manual,” he remembers. “When I was exposed to the microscopic world of proteins, I was amazed by the enzymatic function of these biological machines. The elegant and candid relationship between the structure of a protein and its corresponding function resembled my understanding of how metal parts assembled into an engine can produce incredible amounts of power. I was then intrigued to learn more about the world of proteins and motivated to join Dr. Horvath’s research team in learning a protein mechanistically functions to repair DNA.”

In addition to making discoveries in DNA repair, the Horvath Lab, headed up by principal investigator and SBS Associate Professor Martin Horvath, applies structural methods and biochemistry to make discoveries in Chronic Neuropathic Pain that may lead to the use of non-opioid drugs. For the DNA repair project the lab studies the atomic resolution structure of MutY, [a human gene that encodes a DNA glycosylase], to understand how this enzyme recognizes and removes Adenine in OG:A base pairs.”

Says Utzman, “to better understand the mechanism of MutY, we are interested in learning about the evolution of this enzyme over millions of years. This led us to studying MutY enzymes from microbes at The Lost City Hydrothermal Field, a site similar to conditions in which life may have been conceived on Earth.” Samples from the Lost City have been collected by another SBS professor William “Billy” Brazelton, a unique partnership with marine biology and the unique mineral structures at the bottom of the Mid-Atlantic.

From these samples containing MutY-encoding genes, Utzman and his colleagues were excited to locate microbes that survive off of energy created from a geochemical reaction involving rocks and water, one of the discoveries that would lead to a better understanding of the nature of cancer.

“One of the most valuable assets of the University of Utah is the large amount of cutting-edge research occurring on campus,” says Utzman of his four years in Utah and his seven semesters as a teaching assistant. “I am so thankful for the research opportunities given to me by the U which have paved the way for me to actually have an impact on treating disease and impacting lives.”


Video on Payton Utzman’s 2020 research - “A Structural Analysis of the LC MutY Metagenome”.

Since exchanging leather work gloves in rural America for the rubber-gloved hands of the science researcher, Utzman has learned how to think critically and solve difficult problems. “I am passionate about getting kids interested in science and showing the amazing problems we can solve by blending scientific disciplines with creativity.”

Pursuant to that interest, Utzman worked together with other dedicated STEM students at the U to found the student-led STEM Tutoring program at the U to provide free tutoring to high school students in the greater Salt Lake City area. Not surprisingly, Utzman believes that the future of medicine is molecular. And while his professional ambition is to continue studying the function of proteins to one day help develop therapeutics to treat disease, he is also driven to outreach–-both in elevating the uninitiated to the scientific method (and critical thinking) and in science communication for the public.

The U graduate is quick to reference Dr. Anthony Fauci, the physician-scientist and immunologist serving as the director of the National Institute of Allergy and Infectious Diseases and the Chief Medical Advisor to the President. During the past three years the young scientist saw Fauci as the country’s undisputed spirit guide through the coronavirus pandemic. “His perseverance to help people and communicate scientific truth is inspiring,” says Utzman who finds the short-statured but brilliant (and reportedly fit) octogenarian as his “hero.”

For Utzman, the greatest advice he can give up-and-coming scientists at the U and elsewhere, is to learn how to learn. “The pandemic was a difficult time for all of us, and it was devastating that the virus affected so many lives. I think one of the biggest take-aways from the pandemic was the importance of scientific research and clear communication with the public. My advice for other students would be to learn how to read and to understand research publications.”

Embedded now in the next chapter of his life, Utzman has secured an excellent foundation. The Beta Theta Pi was a two-time Undergraduate Research Opportunities Program (UROP) Scholar, an SBS Research Scholar in 2021 and recipient of the Continuing Student School Scholarship in 2020. Additionally, he was lead author of a paper published in the University of Utah Undergraduate Research Journal.

Though far from the farm fields outside Pullman, Washington, the grease monkey in Utzman apparently is forever. He says that despite long days at the bench studying that “elegant and candid relationship between the structure of a protein structure and its corresponding function” he can still become absorbed by those other metal parts, the ones in trucks and motorcycles that coalesce so intricately–those other machines that can kick out a lot of power, but on the level of a combustion engine.

And this just in from Beantown: Payton Utzman is working on yet another engine–training for the Boston Marathon.

At age 81, Dr. Fauci–known to “kill it” on the treadmill at the gym–would be proud.

Are you a Science Alumni? Connect with us today!

 

Biomimetic Cephalopods

July 11, 2022

Biomimetic Cephalopods

Bringing ancient animals back to life—as robots.

In a university swimming pool, scientists and their underwater cameras watch carefully as a coiled shell is released from a pair of metal tongs. The shell begins to move under its own power, giving the researchers a glimpse into what the oceans might have looked like millions of years ago when they were full of these ubiquitous animals.

This isn’t Jurassic Park, but it is an effort to learn about ancient life by recreating it. In this case, the recreations are 3-D-printed robots designed to replicate the shape and motion of ammonites, marine animals that both preceded and were contemporaneous with the dinosaurs.

 

David Peterman

"Evolution dealt them a very unique mode of locomotion after liberating them from the seafloor with a chambered, gas-filled conch. These animals are essentially rigid-bodied submarines propelled by jets of water."

 

The robotic ammonites allowed the researchers to explore questions about how shell shapes affected swimming ability. They found trade-offs between stability in the water and maneuverability, suggesting that the evolution of ammonite shells explored different designs for different advantages rather than converged toward a single best design.

“These results reiterate that there is no single optimum shell shape,” says David Peterman, a postdoctoral fellow in the University of Utah’s Department of Geology and Geophysics.

The study is published in Scientific Reports and supported by the National Science Foundation.

Bringing ammonites to “life”

For years, Peterman and Kathleen Ritterbush, assistant professor of geology and geophysics, have been exploring the hydrodynamics, or physics of moving through the water, of ancient shelled cephalopods, including ammonites. Cephalopods today include octopuses and squid, with only one group sporting an external shell—the nautiluses.

Before the current era, cephalopods with shells were everywhere. Although their rigid coiled shells would have impacted their free movement through the water, they were phenomenally successful evolution-wise, persisting for hundreds of millions of years and surviving every mass extinction.

“These properties make them excellent tools to study evolutionary biomechanics,” Peterman says, “the story of how benthic (bottom-dwelling) mollusks became among the most complex and mobile group of marine invertebrates. My broader research goal is to provide a better understanding of these enigmatic animals, their ecosystem roles, and the evolutionary processes that have shaped them.”

Peterman and Ritterbush previously built life-sized 3-D weighted models of cone-shaped cephalopod shells and found, through releasing them in pools, that the ancient animals likely lived a vertical life, bobbing up and down through the water column to find food. These models’ movements were governed solely by buoyancy and the hydrodynamics of the shell.

But Peterman has always wanted to build models more similar to living animals.

Diagram of a Biometic Cehalapod.

“I have wanted to build robots ever since I developed the first techniques to replicate hydrostatic properties in physical models, and Kathleen strongly encouraged me as well,” Peterman says. “On-board propulsion enables us to explore new questions regarding the physical constraints on the life habits of these animals.”

Buoyancy became Peterman’s chief challenge. He needed the models to be neutrally buoyant, neither floating nor sinking. He also needed the models to be water-tight, both to protect the electronics inside and to prevent leaking water from changing the delicate buoyancy balance.

But the extra work is worth it. “New questions can be investigated using these techniques,” Peterman says, “including complex jetting dynamics, coasting efficiency, and the 3-D maneuverability of particular shell shapes.”

Three kinds of shells

The researchers tested robotic ammonites with three shell shapes. They’re partially based on the shell of a modern Nautilus and modified to represent the range of ancient ammonites’ shell shapes. The model called a serpenticone had tight whorls and a narrow shell, while the sphaerocone model had few thick whorls and a wide, almost spherical shell. The third model, the oxycone, was somewhere in the middle: thick whorls and a narrow, streamlined shell. You can think of them occupying a triangular diagram, representing “end-members” of different shell characteristics.

“Every planispiral cephalopod to ever exist plots somewhere on this diagram,” Peterman says, allowing the properties for in-between shapes to be estimated.

Once the 3-D-printed models were built, rigged and weighted, it was time to go to the pool. Working first in the pool of Geology and Geophysics professor Brenda Bowen and later in the U’s Crimson Lagoon, Peterman and Ritterbush set up cameras and lights underwater and released the robotic ammonites, tracking their position in 3-D space throughout around a dozen “runs” for each shell type.

No perfect shell shape

By analyzing the data from the pool experiments, the researchers were looking for the pros and cons associated with each shell characteristic.

“We expected there to be various advantages and consequences for any particular shapes,” Peterman says. “Evolution dealt them a very unique mode of locomotion after liberating them from the seafloor with a chambered, gas-filled conch. These animals are essentially rigid-bodied submarines propelled by jets of water.” That shell isn’t great for speed or maneuverability, he says, but coiled-shell cephalopods still managed remarkable diversity through each mass extinction.

“Throughout their evolution, externally shelled cephalopods navigated their physical limitations by endlessly experimenting with variations on the shape of their coiled shells,” Peterman says.

So, which shell shape was the best?

David Peterman

“The idea that one shape is better than another is meaningless without asking the question—‘better at what?’” Peterman says. Narrower shells enjoyed less drag and more stability while traveling in one direction, improving their jetting efficiency. But wider, more spherical shells could more easily change directions, spinning on an axis. This maneuverability may have helped them catch prey or avoid slow predators (like other shelled cephalopods).

Peterman notes that some interpretations consider many ammonite shells as hydrodynamically “inferior” to others, limiting their motion too much.

“Our experiments, along with the work of colleagues in our lab, demonstrate that shell designs traditionally interpreted as hydrodynamically ‘inferior’ may have had some disadvantages but are not immobile drifters,” Peterman says. “For externally shelled cephalopods, speed is certainly not the only metric of performance.” Nearly every variation in shell design iteratively appears at some point in the fossil record, he says, showing that different shapes conferred different advantages.

“Natural selection is a dynamic process, changing through time and involving numerous functional tradeoffs and other constraints,” he says, “Externally-shelled cephalopods are perfect targets to study these complex dynamics because of their enormous temporal range, ecological significance, abundance, and high evolutionary rates.”

Find the full study @ Nature.com.

 

by Paul Gabrielsen, first published in @TheU.