Molecular, Cellular and Developmental Biology

Scientists help students vanquish research-experience Catch-22

Anonymous — Wed, 05 Jun 2024 22:13:25 +0000

Scientists help students vanquish research-experience Catch-22 Anonymous (not verified) Wed, 06/05/2024 - 16:13

Rachel Sauer

In new publication, �� Boulder scientists detail how the SkillsCenter allows students to gain credentials in basic to advanced research skills

It’s an unfortunate truth of higher education that students are not exempt from a classic Catch-22: You need research experience to gain research experience.

“Undergraduates participating in research is a key variable for enhancing their persistence in STEM professions,” explains Zachary Hazlett, a PhD candidate in the University of Colorado Boulder Department of Molecular, Cellular and Developmental Biology. “But to gain access to opportunities in research is not the most straightforward. For a lot of students, these things aren’t baked into their undergraduate degree plan.”

So, students seeking research-focused internships, jobs or higher education opportunities after graduation are often inconsistently prepared with the necessary skills and experience. Hence, the SkillsCenter.

Zachary Hazlett, a PhD candidate in the University of Colorado Boulder Department of Molecular, Cellular and Developmental Biology, is a lead TA on the SkillsCenter proctor team and first author on a paper newly publish in Cell detailing the organizing philosophy, structure and goals of SkillsCenter.

As detailed in a paper newly published in the journal Cell, the SkillsCenter is a modular research skills training course that allows students to “gain training and micro-credentials in the laboratory skills of their choosing.”

In other words, Hazlett says, “what if there was a bridge, something between the classroom and these research spaces that can allow students to gain that necessary experience? That can help equip them to enter those spaces both confidently and competently?”

Module-based curriculum

The SkillsCenter, which is open to students of every major, emerged, in part, from a recognition that undergraduate students have often gained research experiences “by cold-calling faculty members and saying, ‘I’d like to work in research, are there any opportunities in your lab?’” Hazlett says.

Understandably, faculty often ask what their previous experience is, and if a student doesn’t have any, they have to hope they’ll get lucky and find a faculty member willing to teach them.

So, faculty and graduate students in the Department of Molecular, Cellular and Developmental Biology, led by Professor Michael Stowell, began researching and discussing alternative means by which undergraduate students could gain the training and experience they need to gain these critical professional development opportunities.

Based on the principle of “learning by doing,” they designed a module-based curriculum in which modules are scaled by skill level, with appropriate prerequisites, and students can learn at their own self-directed pace. In fall 2021, the first 10 students enrolled in the for-credit SkillsCenter course, working through skills such as lab safety, pipette operation and calibration, centrifugation, buffers and stocks preparation, autoclave sterilization and more.

Today, the course offers training in the laboratory basics as well as advanced training techniques such as polymerase chain reaction, protein expression and purification and various forms of microscopy.

“The course has been designed very carefully,” Hazlett says. “We’ve done our best to build a laboratory space that mimics a traditional research space. Students working in the SkillsCenter gain the experience of what it would be like to be a member of a laboratory research group—in charge of maintaining their space, scheduling equipment, restocking materials, etc. The training modules themselves mimic something a trainee would encounter, with resources to help them and guide them in their conceptual understanding and procedural competence.”

Lab proctors—who are the course instructor, graduate students in the department and a number of undergraduate students who previously took the course—provide on- and off-site guidance for students and assess their work.

What if there was a bridge, something between the classroom and these research spaces that can allow students to gain that necessary experience? That can help equip them to enter those spaces both confidently and competently?"

Learning the scientific process

Through six semesters, SkillsCenter has grown and evolved from the original 10 students to nearly 100 per semester. The lab space is now open from 9 a.m. to 5 p.m. Monday through Friday thanks to increased staffing, and students can work on their modules when their schedule allows.

“It is very important that we have trained lab proctors, and that we instruct our students very carefully on how to engage in this course,” Hazlett says. “Students are instructed that they are responsible for seeking out the resources and guidance they need, and we make sure they know how to access the supports they need.”

Each module requires a certain number of tasks that students complete and submit to proctors for review. Proctors monitor students’ work through each module, give feedback and assess their progress through the scientific process—from hypothesis through notes and observations to interpretation of results.

After completing a module and passing all its required tasks, students receive a certificate for each skill, “so they can collect these certificates and put those skills on their resumes,” Hazlett says, adding that he and his colleagues are working with ORCiD and digital badge organizations to create digital credentials that students can display to future employers. “We also want to embed students’ raw data into those badges, so if an employer wants proof of their skills, they have direct evidence of students’ technical proficiencies.”

Hazlett and his colleagues also are building a network of industry and academic research lab partners to “create an ecosystem for training STEM students. Many students often excitedly explain to me how they have convinced faculty researchers to let them join their labs because of the experiences they have gained in the SkillsCenter.”

Researchers Beiyi Xu, Jennifer Knight, Michael Klymkowsky and Michael Stowell also contributed to the Cell publication.

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In new publication, �� Boulder scientists detail how the SkillsCenter allows students to gain credentials in basic to advanced research skills.

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William B. Wood, pioneering scientist, passes away at 86

Anonymous — Mon, 13 May 2024 20:04:39 +0000

William B. Wood, pioneering scientist, passes away at 86 Anonymous (not verified) Mon, 05/13/2024 - 14:04

A distinguished professor emeritus of molecular, cellular and developmental biology, Wood helped transform �� Boulder into a nationally ranked hub of biomedical science, improved science education and appeared on the debut album of folk legend Joan Baez

William Barry Wood III, who loved science, music, poetry and education in equal parts, and was a distinguished professor emeritus in the Department of Molecular, Cellular and Developmental Biology (MCDB) at the University of Colorado Boulder, passed away on May 9 in Boulder. He was 86.

Bill Wood came to �� Boulder in 1978, leaving a professorship at Caltech to serve as MCDB department chair. He continued in this department as teacher, researcher and administrator until his retirement in 2008. “His clear-thinking mind and kind heart helped to make MCDB a nationally ranked department of modern biomedical science,” said Richard McIntosh, another chair of the �� Boulder department.

In 1972, following important discoveries early in his career, Wood at age 34 became one of the youngest researchers ever elected to the National Academy of Sciences. Later, Wood also emerged as a pioneer in the shifting field of science education. His innovations contributed important ideas and methods for improving the teaching of science at all levels.

William Barry Wood III was a distinguished professor emeritus in the �� Boulder Department of Molecular, Cellular and Developmental Biology.

Bill’s German-born wife, the late Renate H. Wood, became a distinguished Boulder poet, and their sons, Oliver and Christopher, have gained international musical recognition as The Wood Brothers. Wood himself was a masterful guitar player, songwriter and folk musician throughout his life.

In high school, he played in a group with John Hartford, who went on to an impressive career as a revered banjo musician. While still an undergraduate at Harvard in the late 1950s, Bill teamed with Joan Baez on her historic first recording, “Folksingers 'Round Harvard Square.”

The young scientist earned his PhD in 1963 from Stanford University. As a graduate student there, working with Paul Berg in the Department of Biochemistry, Wood learned important skills for the study of macromolecules, such as nucleic acids and proteins. As a young professor at Caltech, he collaborated with Robert Edgar, a geneticist, to study the formation of a virus that infects bacterial cells, known as a “bacteriophage” (for bacteria eater).

Edgar had previously treated samples of T4 bacteriophages with radiation and chemicals that damaged their DNA, making mutations in many different genes. Most of these mutant phages could still infect bacteria, but those bacteria failed to assemble new infective phages as a result of the mutant gene.

Notably, when bacterial cells were simultaneously infected by two phages that were mutant in different genes, infective phages were produced. Thus, the different viral genomes could complement each other, with each providing a functional copy of the gene that was mutant in the other.

Wood invented a method by which one took two populations of bacteria, each infected with a different mutant phage, and broke up the cells in each population to make two samples of bacterial cell cytoplasm, filled with whatever each mutant phage could make.

When these samples were mixed, the materials from one infected population could complement the materials from the other infected population, enabling infective phages to form outside of living bacterial cells. This process became known as “in vitro” (in glass) complementation, because the mutant phages complemented each other without a living cell to help.

This innovation allowed Wood and others to learn by biochemistry and electron microscopy which parts of phage T4 were made by the products of each phage gene. With this information, they could put together a pathway for phage assembly from the protein products of the individual phage genes.

In vitro complementation became an important tool in the hands of many scientists studying virus formation. This valuable contribution helped biologists in the 1960s and ‘70s to elucidate the formation of complex viruses and to significantly combat virus infections.

In the mid-1970s, Wood felt he had contributed what he could to the study of bacterial viruses. His experience combining genetics and biochemistry in the study of hard biological problems led him to seek a new project in an area more complex than the assembly of a virus. One such challenging subject at the time was the problem of how animals develop from a fertilized egg into their adult form.

A distinguished English scientist, Sydney Brenner, had recently introduced the study of a small round worm, Caenorhabditis elegans, into the field of developmental biology. This tiny animal, only 1 millimeter long, lives in rotting fruit. It can be fed on bacteria in the laboratory, and it grows to adulthood in just three days, making it easy, cheap and fast to study.

Several young scientists had already gone to Brenner’s lab to learn how to study C. elegans and brought their projects back to labs in the United States. One of these scientists was David Hirsh, who was on the faculty at MCDB in Boulder, so Wood arranged to do a sabbatical in Hirsh’s lab.

During that year, Wood worked with Hirsh and several of his students to make numerous mutant strains of worms. They identified several that inactivated genes important for the early stages in worm development. Particularly informative were their temperature-sensitive mutants, which developed well when grown at temperatures as low as 60^o, but displayed interesting developmental defects when grown at elevated temperatures closer to 85^o.

These mutants identify genes whose products are needed for normal development. Therefore, they have subsequently been studied by numerous labs to elucidate key players and pathways in development.

Excited by his research experience in Boulder, Wood considered setting up a lab at Caltech to study worm development. But the �� Boulder MCDB department was seeking a chair who could lead the department in valuable new directions. Several enthusiastic members of the department flew to Pasadena, unannounced, and convinced Wood to move his work and his family to Colorado.

In Boulder, Wood quickly assembled an excellent lab of his own, and he also organized the hiring of superior scientists engaged in the same process of using genetic manipulation to study complex biological problems.

At the time, experts were debating whether the developmental fates of individual cells in early embryos are determined by internal factors that are packaged into those cells or determined by external cues from neighboring cells. Wood’s group found compelling evidence for both internal factors and external cues, a finding that has been borne out across organisms.

Wood’s lab discovered a new type of organelle that is not bounded by a membrane. These organelles, called "P granules” in worms, are examples of internal factors that are delivered to particular cells in early embryos and are critical for the normal development of those cells. P granules are the founding members of an ever-growing list of liquid-like condensates that serve diverse roles across organisms.

Finally, Wood himself studied how an organism develops its left-right axis, which in worms becomes apparent when embryos have only six cells. He documented that one-cell embryos already show signs of knowing their left side from their right. From then on, his Colorado license plate read WORMS1.

Singing with Joan Baez

The eldest of five children, Wood grew up in St. Louis, where his father, a renowned physician and medical researcher, taught at Washington University. In 1955, Dr. W. Barry Wood moved his family to Baltimore, when he became the head of the Johns Hopkins Medical School. The elder Wood had been an All-American quarterback at Harvard and a nationally ranked tennis player. Coming from an athletic family, Wood won the Maryland State Junior Tennis Championship at age 17 and played on Harvard’s varsity tennis team.

While an undergraduate chemistry major at Harvard, Wood also devoted time to music, playing his guitar in a group called The Raunch Hands and hosting a weekly program on the campus radio station. There he met singer Joan Baez, then in her first year of college. In 1959, Bill and Ted Alevizos teamed with the future folk legend to make a record now renowned as her debut album. The next year, Joan produced her first solo album, “Joan Baez,” while Bill opted for a career in science.

In an interview conducted at Stanford in 2015, Wood reflected on that early fork in the road. He recalled with a modest smile his parting with Joan Baez: “It was very clear which of us should go to grad school at Stanford and which of us should go to the Newport Folk Festival and become a star.” Pausing, he added: “I have to say, with all due respect to the scientists, that was the most fun I ever had, singing with Joan Baez.”

Wood’s parents were both educators, and throughout his career Wood was interested in finding ways to teach that would help students at all levels learn science efficiently and well. “When my kids started school in the 1970s, I got interested in what they were going to experience, and I was impressed by a book called 'How Children Fail' by John Holt," Wood said. "His message was that for kids to learn, they need to be doing things, not just listening to a teacher. That was my introduction to active learning.”

Textbooks were focused on memorizing pathways, names of enzymes and so on, and I wanted to try to put some life into it.”

Toward the end of his career, Wood turned his full attention to research on science education. In harmony with work spearheaded by Bruce Alberts from the National Academy of Sciences and by Nobel Laureate Carl Wieman in the Department of Physics at �� Boulder, Wood helped to develop a “questions” approach to teaching, suitable for any science pedagogy.

To challenge and assist college-level science teachers, he worked with Dr. Jo Handelsman, who later became a science advisor for President Barak Obama. The pair started the National Institutes of Undergraduate Education in Biology. Now known as NIST, this thriving organization has had far-reaching effects, helping to train thousands of faculty, especially at R1 institutions, how to teach actively.

“Textbooks were focused on memorizing pathways, names of enzymes and so on, and I wanted to try to put some life into it,” Wood said. With “active learning,” lectures become participatory events, and students retain more than when they are simply spoken to. The amount of material presented is reduced, but the amount students retained is greater.

This approach has been adopted widely, and it follows the Chinese principle of instruction, stated as a motto in Wood’s first biochemistry book: “I hear, and I forget; I see, and I remember; I do, and I understand.” In 2016, the Genetics Society of America gave Wood its Elizabeth W. Jones Award for Excellence in Education, calling him “a pioneer in the reform of science teaching.”

The Society cited Wood’s role in the development of the influential National Academies Summer Institutes for Undergraduate Education in Biology and his service as editor-in-chief of CBE-Life Sciences Education, published by the American Society for Cell Biology. “Bill is not only an excellent educator himself,” states Rachelle M. Spell of Emory University, “he helped start a revolution across STEM teaching.”

In 2018, Jenny Knight, an associate professor of molecular, cellular and developmental biology at �� Boulder, served as president of the Society for the Advancement of Biology Education (SABER). That year, SABER instituted the Bill Wood Graduate Student Talk Award, which was very dear to Wood’s heart. According to Knight, who knew Wood as her mentor and colleague, he had “a passion for supporting the next generation of researchers.”

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College of Arts and Sciences professors named 2024 American Academy of Arts and Sciences members

Anonymous — Wed, 24 Apr 2024 19:33:50 +0000

College of Arts and Sciences professors named 2024 American Academy of Arts and Sciences members Anonymous (not verified) Wed, 04/24/2024 - 13:33

Min Han and Arthur Nozik join a distinguished cohort that includes George Clooney and Jhumpa Lahiri

Min Han, a University of Colorado Boulder distinguished professor of molecular, cellular and developmental biology, and Arthur Nozik, a �� Boulder research professor emeritus of chemistry, have been named 2024 members of the American Academy of Arts and Sciences, a cohort that includes Kristine Larson, a �� Boulder professor emeritus of aerospace engineering sciences.

The 250 members elected in 2024 “are being recognized for their excellence and invited to uphold the Academy’s mission of engaging across disciplines and divides,” according to an American Academy of Arts and Sciences announcement. The Academy was founded in 1780 to “help a young nation face its challenges through shared purpose, knowledge and ideas.”

The American Academy of Arts and Sciences was founded in 1780 by John Adams, John Hancock and 60 colleagues who "understood that a new republic would require institutions able to gather knowledge and advance learning in service to the public good."

“We honor these artists, scholars, scientists and leaders in the public, non-profit and private sectors for their accomplishments and for the curiosity, creativity and courage required to reach new heights,” noted David Oxtoby, president of the Academy, in the announcement. “We invite these exceptional individuals to join in the Academy’s work to address serious challenges and advance the common good.”

The 2024 cohort also includes actor and producer George Clooney, author Jhumpa Lahiri and Apple CEO Tim Cook.

Han’s research uses Caenorhabditis elegans and mouse models to study diverse biological problems related to animal development, stress response, nutrient sensing and human disease by applying both genetic and biochemical methods.

He and his research colleagues in the Han Lab work to identify and analyze mechanisms by which animals sense the deficiency of specific nutrients, including lipids, nucleotides and micronutrients, and regulate development, reproductivity and food-related behaviors.

Nozik, who also is a senior research fellow emeritus at the National Renewable Energy Laboratory in Golden, has researched the basic phenomena at semiconductor-molecule interfaces and the dynamics of electron relaxation and transfer across these interfaces. The �� Boulder Renewable and Sustainable Energy Institute’s Nozik Lecture Series is named in his honor.

Previous years’ �� Boulder nominees include Henry Kapteyn, Karolin Luger, Alison Jaggar and Natalie Ahn, among many others. In all, 42 �� Boulder faculty members have been named American Academy of Arts and Sciences fellows.

Top image: Min Han (left) and Arthur Nozik.

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Min Han and Arthur Nozik join a distinguished cohort that includes George Clooney and Jhumpa Lahiri.

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�� Cancer Center leaders aim to use novel molecule to fight cancer

Anonymous — Thu, 29 Feb 2024 15:59:43 +0000

�� Cancer Center leaders aim to use novel molecule to fight cancer Anonymous (not verified) Thu, 02/29/2024 - 08:59

Mark Harden

Tin Tin Su of �� Boulder and Antonio Jimeno of the �� School of Medicine say acceleration-initiative funds will help speed a promising, developed-in-Colorado cancer therapy to patients

After working eight years on a new way to attack some cancers, a pair of University of Colorado Cancer Center researchers are closer to their goal of bringing their therapy to patients—as one of nine research endeavors receiving funding from the Anschutz Acceleration Initiative (AAI).

The project is led jointly by Tin Tin Su, co-leader of the cancer center’s Molecular and Cellular Oncology Program and professor of molecular, cellular and developmental biology at the University of Colorado Boulder, and Antonio Jimeno, a co-leader of the �� Cancer Center’s Developmental Therapeutics Program and professor in the �� Department of Medicine's Division of Medical Oncology.

Tin Tin Su, a �� Boulder professor of molecular, cellular and developmental biology, discovered that a molecule found in the firecracker bush can be synthesized to target cancer stem cells.

Jimeno says it’s significant that the AAI award is for a potential cancer therapy “that was discovered in Colorado and will use Colorado funds from a Colorado donor to help Colorado cancer patients.”

He adds: “Here at the �� Cancer Center, we can get things done really well and really quickly, provided we have the focus and the resources. And this grant provides both.”

Their work involves the use of a synthetic small molecule called SVC112, which has been shown to effectively target cancer stem cells in head and neck cancers, the main focus of Jimeno’s research lab.

Cancer stem cells produce cells that make up most of a tumor’s bulk. They often are resistant to traditional therapies such as radiation and chemotherapy and can recover from treatment to produce more tumor cells. The U.S. Food & Drug Administration has approved the use of protein synthesis inhibitors that slow or stop cancer cell growth, but they can be toxic to healthy cells as well as cancer cells.

SVC112 was originally synthesized by SuviCa, Inc., a Boulder-based biotechnology company co-founded by Su. It’s based on the chemical bouvardin, found in the firecracker bush, Bouvardia ternifolia, a red-flowering plant that grows in the Southwest and Mexico.

The discovery in Su’s research lab at �� Boulder of bouvardin’s remarkable ability to prevent regeneration of tissues in the fruit fly led to the current studies.

Previous research by Jimeno, Su, and others showed that SVC112 can keep cancer stem cells from manufacturing more tumor cells. The pre-clinical research indicated that SVC112 can be more effective than the FDA-approved protein synthesis inhibitor homoharringtonin (HHT), and with less toxicity, while also increasing the effects of radiation treatment.

“It’s effective in ways that other drugs are not,” Su says. “This compound has shown efficacy in squamous head and neck cancer, in salivary gland cancer, colorectal cancer, and leukemia models. This is very exciting, because it proves the biologic point that multiple tumor types rely on the same mechanisms, the same proteins, to become invasive, to grow and to metastasize.”

This is very exciting, because it proves the biologic point that multiple tumor types rely on the same mechanisms, the same proteins, to become invasive, to grow and to metastasize.”

Su points out that SVC112 passed three reviews to be approved to receive milestone-based support from the National Cancer Institute’s (NCI) Experimental Therapeutics Program (NExT) in 2023, providing resources for SVC112’s development. NCI is part of the National Institutes of Health.

Jimeno says that the five-year AAI grant will help fund the arduous next steps in developing SVC112. First, the researchers will conduct pre-clinical experiments leading to an investigational new drug filing to the FDA within two years. Next, he says, plans call for a first-in-human Phase 1a clinical trial in cancer patients “to determine the safe, optimal way of delivering this to humans, employing all the clinical-trials capabilities of our university, including the Cancer Center Clinical Trials Office,” followed by a Phase 1b trial.

Cancers to be targeted in later stages of the clinical trials may change based on early results, if the researchers see patients with certain cancers responding especially well, Jimeno says.

The AAI recipients were announced in January by �� School of Medicine Dean John J. Reilly, Jr., MD, during his annual State of the School address.

Mark Harden is a writer for the Anschutz School of Medicine, which published a slightly different version of this story.

Top image: Bouvardia ternifolia, or firecracker bush (Photo: U.S. Forest Service)

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Tin Tin Su of �� Boulder and Antonio Jimeno of the �� School of Medicine say acceleration-initiative funds will help speed a promising, developed-in-Colorado cancer therapy to patients,

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Small but not simple, bacteria compute without thinking

Anonymous — Fri, 01 Sep 2023 21:26:41 +0000

Small but not simple, bacteria compute without thinking Anonymous (not verified) Fri, 09/01/2023 - 15:26

Rachel Sauer

New �� Boulder research shows that bacteria harness physical laws to operate at the edge of chaos and use calcium to independently diversify and find a place to settle down

Let’s talk about the bacteria in our colons.

Like all life on this planet, their main goal is to replicate their genome, passing it on to the next generation. But hostile environments like the colon force them to make tough choices: Hunker down here or swim farther downstream in hopes of greener pastures?

Meanwhile, all their kin are making the same calculation. Each has the same genome but can’t follow the same instruction manual or else they’ll all land on the same spot. They must diversify. So, how does a single-cell organism lacking the benefit of billions of neurons know how to do that?

Newly published research finds that bacteria—and not just the kinds in our colons, but many types in many environments—use changes in calcium, controlled through a process called “self-organized criticality,” to spontaneously diversify without the need for communication between cells. Bacteria use calcium not only in governing the transition to a biofilm, but in movement, maintaining cell structure and in infection.

Christian Meyer, a postdoctoral fellow in the University of Colorado Boulder Department of Molecular, Cellular and Developmental Biology, researched how bacteria use calcium to diversify.

Understanding how calcium is regulated in bacteria may have significant future implications for, among other applications, treating harmful biofilms that can form on surfaces. Further research may help scientists interrupt a bacterium’s calcium dynamics, perhaps preventing it from settling on a surface in the first place.

“Bacteria have so much to teach us,” says Christian Meyer, a postdoctoral fellow in the University of Colorado Boulder Department of Molecular, Cellular and Developmental Biology who completed the research with former �� Boulder assistant professor Joel Kralj. “There’s a fallacy in assuming that because something is small, it’s simple. Bacteria are using statistical mechanics to run computations instantaneously that I run over an entire weekend on my computer.”

Not more evolved than bacteria

In fact, Meyer’s research was inspired, in part, by the prevalent notion that humans are the pinnacle of evolution and the idea that “we’re more evolved than ________”—than amoebas, than earthworms, than bacteria.

“That’s not at all what evolutionary theory is saying,” Meyer notes. “The theory is that you, as a human, would make a horrible worm. Each unto their own niche. There are lots of systems in the natural world that operate without ‘intelligence,’ by which I mean that bacteria aren’t sitting there with a billion neurons at their disposal to figure out how much calcium they should let in right now. They have to do that rapidly and in changing environments, but also energy efficiently, and do it instantaneously—they’re not thinking.”

Originally, Meyer and his research colleagues studied antibiotics and how they modify the electrophysiology—or the electrical properties of cells that include current and voltage—of bacteria. They showed that E. coli bacteria, when treated with certain antibiotics, respond with changes in membrane potential.

In hundreds of videos of antibiotic-treated bacteria, the scientists watched calcium, as a marker of cell membrane voltage, going in and out of the cell. Instead of general randomness in that process, they saw power laws at work. Power laws describe the probability of an event happening as a function of its magnitude or duration. For example, the relationship between the probability and magnitude of an earthquake follows a power law, with large earthquakes being less likely than small ones.

Through further research with strains of E. coli, B. subtilis and P. putida bacteria, they found that calcium fluctuations resulted from a property known as self-organized criticality (SOC). SOC is a general property of many natural systems that are poised at the boundary between two phases without external control. Rather than separate states of matter, the phases are defined as different dynamical regimes, and often SOC systems are poised at the boundary between ordered and chaotic dynamics—what has been described as “order at the edge of chaos.”

Using self-organized criticality

Meyer and Kralj found that SOC can explain how bacteria cells exist on a knife’s edge between very high levels of calcium outside the cell and calcium levels that are about 100,000 times lower inside the cell. At high levels, calcium can be cytotoxic, meaning it can damage or kill cells. So, the bacteria‘s membranes operates somewhat like a dam, opening and closing rapidly and often—but not in a consistent pattern—to pump calcium in and out.

Bacteria expressing a fluorescent calcium sensor.

The research findings also suggest an evolutionary advantage of SOC, because it provides a way for individual bacteria to diversify, even without communicating with one another. SOC could be compared to a random number generator inside each bacteria cell, one that’s power law-based “so big events are more likely than they would be otherwise,” Meyer says.

“Because of this, going back to the example of bacteria in the colon, a bacterium will swim farther down the colon than it would if it was just randomly swimming. This is an extremely efficiently search strategy, to use power law-based searches in a domain. From my perspective, I think how incredible it is that they’re using a physical process to run computations to figure out what they should be doing, all without talking to each other or ‘thinking’.”

While understanding how calcium dynamics in bacteria result from SOC is an important step, further research will need to study how to target calcium while leaving a bacterium’s membrane electrical voltage intact. Then researchers can begin working toward applications like treating harmful biofilms.

“I’ve really grown to admire what bacteria are capable of doing,” Meyer says. “Imagine being a one-femtoliter cell (one-quadrillionth of a liter) and having to survive in the crazy world we live in with all the changes in temperature and pH and nutrients. It’s a hard world, but they’ve come up with incredibly elegant solutions to the complex challenges they face.

“In some ways, I’ve been inspired thinking how can we co-opt some of these natural processes for solving some of the issues humans face and do it in an intelligent way, things bacteria figured out a long time ago. SOC systems are an interesting mixture of flexible yet robust without the need for constant tuning. These seem desirable properties for many anthropogenic systems, from AI to social networks. I’ve come to appreciate bacteria as good examples of combating that fallacy of we are the pinnacle of evolution. They have amazing secrets to teach us, we just have to look at them.”

Top image: AI-generated picture of bacteria

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New �� Boulder research shows that bacteria harness physical laws to operate at the edge of chaos and use calcium to independently diversify and find a place to settle down.

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Genetic ‘freeloaders’ may play key role in immune system

Anonymous — Tue, 29 Aug 2023 17:24:53 +0000

Genetic ‘freeloaders’ may play key role in immune system Anonymous (not verified) Tue, 08/29/2023 - 11:24

Rachel Sauer

�� Boulder researcher Edward Chuong recently received an international award for his lab’s work studying transposons in the human genome

Our genome, it turns out, is full of freeloaders—selfish elements that behave like viruses, because they exist to copy and paste themselves, but unlike viruses, they can’t leave the cell.

Called transposons, they compose about 50% of the human genome. In fact, most life on Earth contains transposons in their genomes and scientists theorize that transposons have existed since the early beginnings of life on this planet.

However, just because transposons can’t leave a cell doesn’t mean they’re merely “junk DNA” or bugs in the genetic code that can’t affect the cell. Edward Chuong, an assistant professor of molecular, cellular and developmental biology at the University of Colorado Boulder, has found that transposons play a role in the human immune system and how cells communicate within it.

Chuong recently was recognized for this work by the International Cytokine & Interferon Society with the 2023 ICIS-Regeneron New Investigator Award for Excellence in Cytokine and Interferon Research. The award will be presented in October at the Cytokines 2023 conference in Athens, Greece.

Researcher Edward Chuong recently earned the 2023 ICIS-Regeneron New Investigator Award for Excellence in Cytokine and Interferon Research from the International Cytokine & Interferon Society.

Chuong and his research colleagues in the Chuong Lab have studied how transposons can affect signaling by interferons, which are proteins produced by many types of cells in response to infection. They found that transposons can both help and hinder the interferon response of cells.

“One way to think about transposons is they’re inherently parasites that can occasionally be domesticated to help their hosts,” Chuong says. “We found in certain cells that when we deleted the transposon but not the gene, we broke the function necessary for an antiviral response. We showed that cells could no longer respond to a virus because they were missing this transposon, which was an interesting twist to the evolutionary arms race against disease. We’re starting to see we’ve gotten some help from very old viral infections to fight new ones.”

Not all junk DNA

Chuong and his colleagues have extensively studied endogenous retroviruses, a type of transposon originating from past retroviral infections. A retrovirus, one of which is HIV, is a type of RNA virus that has a special enzyme to convert its genetic information into DNA. When it invades a cell, it can insert that DNA into the host cell’s DNA and fundamentally change its genome. When this happens to cells that give rise to sperm or egg cells, the retrovirus can become a part of the next generation’s genome.

They identified MER41, an ancient retrovirus that invaded the genomes of humans’ primate ancestors more than 50 million years ago and found that it had been “domesticated” to regulate important immune-defense genes, including the antiviral gene AIM2.

“If we consider that key parts of our DNA are not human in origin, it implies that we are all genetically modified organisms, being changed in important ways by ancient transposons and viruses,” Chuong says. “What we think of as ‘human’ DNA is likely to be less than half of the human genome sequence. Throughout our evolutionary history, transposons have been invading and replicating within our genome, and eventually going extinct. Yet, each invasion leaves behind a ‘fossil record’ of potentially thousands of copies in the genome.

“So, the vast majority of these transposons are junk DNA, but not all of them. We thought that some of them must be important and must have shaped our evolution and biology.”

A classic example of this is a set of genes called RAG1 and RAG2, which are responsible for shuffling human DNA to generate the virtually infinite variation in antibodies for adaptive immune response. Researchers have learned that these proteins originated from what was once a parasite “and our evolutionary ancestors were able to co-opt these proteins for an immune function,” Chuong says. “Transposons are a pivotal source of new genetic material and are increasingly appreciated to be important for adaptation and change in DNA.”

Understanding immune response

Chuong’s research on transposons’ role in the immune system has looked at how they can regulate immune signaling and how they affect the communication system cells use to coordinate immune response.

We’re starting to see we’ve gotten some help from very old viral infections to fight new ones."

“When you get infected by a virus, immune cells detect that and release many cytokines, which are signaling proteins that help control inflammation; one of the most important of these is interferon,” Chuong says. “Other cells will detect interferon using a receptor on the outside of the cell, which causes the activation of immune genes.

“But these are not genes that you want on all the time; that’s what would lead to autoimmunity. So, when a cell is stimulated with interferon, several hundred genes with antiviral and inflammatory functions become activated.”

Activating interferon activates transcription factors, which are proteins that modulate how a cell translates DNA to RNA. They travel into the cell’s nucleus and trigger gene expression, or the process by which instructions in DNA are turned into a functional product like protein.

“The work that this award recognizes shows that a lot of these regulatory elements, you can think of them as switches or knobs,” Chuong says. “They’re not coding DNA, but often are around or upstream of a gene. We’ve found that these non-coding regulatory elements that control immune gene expression are themselves derived from transposons.”

This research has potential implications for understanding and treating many diseases, including cancer. Chuong and his colleagues have found that some transposons that are usually inactive in healthy cells become reactivated in tumor cells. Future research may delve into what that means for making the immune system more susceptible to therapy.

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�� Boulder researcher Edward Chuong recently received an international award for his lab’s work studying transposons in the human genome.

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Pioneering biologist elected to National Academy of Sciences

Anonymous — Fri, 12 May 2023 18:13:20 +0000

Pioneering biologist elected to National Academy of Sciences Anonymous (not verified) Fri, 05/12/2023 - 12:13

Lisa Marshall

Gia Voeltz, �� Boulder professor of molecular, cellular and developmental biology, changed the way we visualize cells

Think back to your middle school biology days, and you might recall textbook images of a circular cell, its internal organs, or “organelles,” spread out across it with little contact or interaction.

Shortly after cell biologist Gia Voeltz arrived at the University of Colorado Boulder in 2006, she peered through one of the world’s strongest electron microscopes and saw something different: One of those organs, the endoplasmic reticulum, was actually touching the others, seemingly influencing their position, growth and behavior.

The discovery forever changed our understanding of the structure and function of cells, helped ignite new interest in the field of cell biology and is now shedding new light on what goes wrong to cause diseases, including neurodegenerative diseases.

At the top of the page: Gia Voeltz in her lab. Above: Gia Voeltz.

This month, it also earned Voeltz a place in the National Academy of Sciences, one of the highest professional honors a scientist can achieve.

The NAS also elected theoretical physicist Anna Maria Rey, a professor adjoint of physics and fellow with the National Institute of Standards and Technology and JILA, to the organization. (Read more about that here).

“This is a huge recognition not just for me and my lab members but for our entire community,” said Voeltz, a professor of molecular, cellular and developmental biology (MCDB). “I feel so fortunate that I’ve had the kind of environment that we have here at �� to be able to do this work.”

Voeltz’ research centers around the endoplasmic reticulum (ER), an organelle historically drawn as something resembling a stack of pancakes and set apart from the kidney-shaped mitochondria (the cell’s energy centers) and round endosomes (which regulate cell growth).

Keith Porter, who chaired the MCDB department in the late 1960s and established what remains one of the world’s most sophisticated electron microscopy facilities on campus, coined the term “endoplasmic reticulum” in the early 1950s.

But until Voeltz’ discovery, the ER was considered a workhorse, viewed as a simple protein factory set apart from the intracellular action.

In reality, her lab discovered, the ER is more like a lacy and dynamic coral, spread out across the cytoplasm with the cell’s other organs, clinging to it like ornaments on a tree. Instead of those organs’ being isolated and doing their own thing, they are all connected and communicating through the ER.

“Everyone thought they knew what the ER did, but it turns out it does a lot more than we thought,” said Voeltz. “And it is extremely medically relevant.”

In 2018, Voeltz was named a Howard Hughes Medical Institute (HHMI) investigator and awarded $8 million to take her research wherever she wanted.

She and her trainees have since doubled down on exploring what happens when things go wrong with the ER.

For instance, she notes, a host of deadly RNA viruses including SARS CoV-2, the virus that causes COVID 19, wrap themselves in the ER membrane “like an invisible cloak” to evade the immune system and replicate.

Voeltz and her students are among a handful of groups in the world exploring the ER’s role in viral replication and imagine a day when that process could be disrupted to prevent or treat such infections.

Meanwhile, she’s also looking into how certain proteins regulate the critical interaction between the ER and other organelles, and what happens when those proteins are mutated in developing brain and nerve cells.

It’s really the first step in understanding how a mutation in a gene can lead to a mutant protein and affect the whole biology of the neuron. If we could somehow correct that, we could potentially treat a host of diseases that are currently incurable.”

The lab is currently studying the roots of an incurable childhood neurodegenerative disorder called hereditary spastic paraplegia, HSP, that weakens, stiffens and causes tremors in the legs and can also cause blindness and cognitive impairment.

In a recent paper, they identified a key protein that influences the shape of the ER and, in turn, influences how axons—nerve fibers that carry signals from the brain to the limbs—form.

When the protein is missing or mutated, they found, a domino-effect occurs, with the ER misshapen, other organelles disrupted and axons developing improperly.

“It’s really the first step in understanding how a mutation in a gene can lead to a mutant protein and affect the whole biology of the neuron. If we could somehow correct that, we could potentially treat a host of diseases that are currently incurable.”

For now, what Voeltz is most proud of is the way her research has shaped biology education.

Already, some textbook illustrators have begun to draw the cell in a different way because of her work. She hopes that continues.

“I look forward to the day when the front cover of a cell biology textbook has a picture of organelles that are all interacting with each other. That would make me really proud.”

Gia Voeltz, �� Boulder professor of molecular, cellular and developmental biology, changed the way we visualize cells.

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Artist vivifies the pain, diaspora and tragedy of Kashmir

Anonymous — Wed, 21 Dec 2022 18:25:30 +0000

Artist vivifies the pain, diaspora and tragedy of Kashmir Anonymous (not verified) Wed, 12/21/2022 - 11:25

Clint Talbott

Shloka Dhar, who majored in art practices and molecular, cellular and developmental biology, is the College of Arts and Sciences’ outstanding graduate for fall 2022

Shloka Dhar began her studies at the University of Colorado Boulder with a plan: take a pre-med track to become a doctor. Four-and-a-half years later, she’s chosen a path that better reflects who she is and where she is from.

Last week, Dhar graduated with a BA in molecular, cellular and developmental biology, along with a Bachelor of Fine Arts in art practices, summa cum laude. She also has been named the outstanding graduate of the College of Arts and Sciences for fall 2022.

At the top of the page: Shloka Dhar smiles in front of her thesis project, which is titled Mõaj. Above: Before completion, Dhar poses next to her project's metal framework, which reflects the topography of the Himalayas in Kashmir, her family homeland.

What changed, Dhar told fellow honors graduates last week, was that she realized her interests were broader than medicine. Dhar has worked in a lab studying muscle stem cell regeneration in mice. Although that was exciting work, Dhar said, she felt she was not doing justice to who she is as a person.

“For as long as I have remembered, I have always loved biology, and I have always loved art,” she said. “The rest of the world thought art and science are diﬀerent career paths, and for a moment, I believed them.”

“But I did not want to settle for one or the other, because I truly believe that they are intertwined,” she continued. Her honors thesis in sculpture thus combined the two, exploring ideas of genetic memory, preservation, loss, physical displacement and genocide.

Dhar was born in Bokaro Steel City in India, an industrial center, but her roots are in Kashmir, the disputed war-ravaged territory at the northern juncture of India and Pakistan.

Kashmir, Dhar notes, “is a war zone that I have never been able to visit, and now I am a citizen of a country that I feel does not want me. I do not belong where I am now, stuck in a liminal space. My art documents my explorations through this in-betweenness, of expeditions through my personal identity and out into my interactions with the physical world.”

Dhar’s mother fled the Kashmiri Pandit Genocide of 1990, which was conducted by Islamic extremists, she notes in her thesis. Legally, Dhar is an Indian immigrant who has American citizenship. “However, I really consider myself a displaced Kashmiri.”

Dhar reflects that her identity is constructed of many parts, “many of which seem to clash.”

“The identity I grew up with is disintegrating, and in the midst of attempting to reconstruct it, I ask myself, ‘How can I be a Kashmiri when there is no more Kashmir?’”

Her thesis project, titled Mõaj, is “a continuing discourse about my experiences of physical and psychological displacement, genetic memory, a reclamation of the land, and reconnection with my ancestors,” she writes.

Mõaj is a sculpture constructed of more than 550 feet of steel and traditional Indian fabric. It reflects the Himalayan topography of Kashmir, and it “embodies the heaviness of these ideas,” she states.

Through her art, she says, “I can visually understand the nature and extent of the psychological pain and intergenerational trauma present in my body. It is given a physical form that persistently highlights the beauty of my culture so that I am able to acknowledge the pain.”

My art is my most successful method of communication, and the most important message I want to communicate is that I am here. I persist not only despite my cultural history, but because of it.

“Both pain and beauty must be present so that neither is gone unappreciated. My art is my most successful method of communication, and the most important message I want to communicate is that I am here. I persist not only despite my cultural history, but because of it.”

Yumi Janairo Roth, a professor in sculpture and post-studio practice who was Dhar’s thesis advisor, says that she and fellow faculty member Richard Saxton are "incredibly proud of Shloka.”

Roth adds: “Mõaj is a remarkable work that, in many ways, is semesters in the making, bringing together issues related to the Kashmiri diaspora, identity, epigenetic memory and community that Shloka has been exploring for a while. We're excited for what the future holds for her.”

Shloka Dhar, who majored in art practices and molecular, cellular and developmental biology, is the College of Arts and Sciences’ outstanding graduate for fall 2022.

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Big grant supports students transferring from two-year colleges

Anonymous — Thu, 15 Dec 2022 22:26:04 +0000

Big grant supports students transferring from two-year colleges Anonymous (not verified) Thu, 12/15/2022 - 15:26

�� Boulder, Front Range Community College among 104 recipients of Howard Hughes Medical Institute funding to boost inclusion in STEM fields

Students who are transferring from Front Range Community College (FRCC) to the University of Colorado Boulder might soon find the process easier, thanks to a six-year $470,666 Howard Hughes Medical Institute (HHMI) grant, which supports the collaboration between the two institutions.

That grant is part of an $8.8 million grant for �� Boulder’s larger learning community collaboration, which focuses on successful transfer of community college students and aims to improve the diversity of students in the sciences nationwide.

“This HHMI grant recognizes the partnership that we are building with colleagues across the �� Boulder, FRCC Westminster and FRCC Boulder County Campuses,” said Lee Niswander, professor and chair of the �� Boulder Department of Molecular, Cellular and Developmental Biology.

“We are excited to be a part of a nationwide learning community to discuss and implement best practices to support the transfer of students from community college to a four-year institution to earn a baccalaureate degree in the life sciences.”

We are excited to be a part of a nationwide learning community to discuss and implement best practices to support the transfer of students from community college to a four-year institution to earn a baccalaureate degree in the life sciences.

The �� Boulder/FRCC team will work on topics related to peer-mentoring and student research experiences in the life sciences.

“We are pleased to have provided FRCC students with summer research experiences over the past two years as part of �� Boulder faculty research teams, and we are preparing to select a new set of FRCC students for summer 2023,” Niswander added.

“This partnership will provide FRCC students a great opportunity to participate in cutting-edge research on the �� Boulder campus, said Cheryl Hoke, chair of FRCC’s Westminster Campus Science Department.

“Undergraduate research experiences enhance students’ perceptions of themselves as scientists, help prepare them to transfer to a university setting, and lead to greater degree completion in STEM (science, technology, engineering and mathematics). We are excited to continue our collaboration with �� faculty in support of students,” she said.

The Colorado partnership is among those from 104 colleges and universities that received grants through HHMI’s Inclusive Excellence 3 (IE3) initiative to continue their “critical work to build capacity for inclusion of all students in science.”

These grants—totaling more than $60 million over six years—along with previous funding to IE1 and IE2 schools, now support 161 schools nationwide as they design experiments that hope to improve the introductory undergraduate science experience, HHMI states.

“Sustaining advances in diversity and inclusion requires a scientific culture that is centered on equity,” said Blanton Tolbert, HHMI’s vice president of science leadership and culture. “In science education, increasing the number of individuals from underrepresented backgrounds must go hand in hand with creating inclusive learning environments in which everyone can thrive.”

In science education, increasing the number of individuals from underrepresented backgrounds must go hand in hand with creating inclusive learning environments in which everyone can thrive.

In preparing IE3 pre-proposals, each school picked one of three broad challenges to address:

How can schools make the content of the introductory science experience more inclusive?
How can schools evaluate effective inclusive teaching, and then use the evaluation in the rewards system including faculty promotion and tenure?
How can we create genuine partnerships between two- and four-year colleges and universities so that transfer students have a more inclusive experience? (This is the challenge targeted by the ��/FRCC collaboration.)

The challenges were carefully selected to help the schools focus on designing strategies to prevent the massive loss of talent from STEM that occurs during the college years, HHMI states.

Of the nearly 1 million students who enter college annually intending to study STEM, more than half will not complete a STEM bachelor’s degree, student data show. Those who leave STEM are disproportionately students who are first in their family to attend college, students who begin at community colleges, and students from historically excluded ethnic and racial groups.

The IE3 initiative targets the introductory STEM experience because that is when most of the departure from STEM occurs, HHMI observes. For non-transfer students, this departure from STEM typically occurs during or immediately after the first year in college.

Besides Niswander, the �� Boulder collaborators include Julie Graf and Lisa Romero de Mendoza, both with the Biological Sciences Initiative.

�� Boulder, Front Range Community College among 104 recipients of Howard Hughes Medical Institute funding to boost inclusion in STEM fields.

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L. Andrew Staehelin, �� Boulder molecular biologist, dies at 83

Anonymous — Wed, 05 Oct 2022 19:12:58 +0000

L. Andrew Staehelin, �� Boulder molecular biologist, dies at 83 Anonymous (not verified) Wed, 10/05/2022 - 13:12

Professor emeritus remembered for his ability to present important material expertly and for his humor, intelligence and interest in people

L. Andrew Staehelin, a longstanding member of the University of Colorado Boulder Department of Molecular, Cellular and Developmental Biology (MCDB) passed away on Sept. 28, 2022. He was 83.

Staehelin came to �� Boulder as an assistant professor in 1970, was promoted to full professor in 1978, and became a professor emeritus in 2006. Throughout his career, he was a devoted and skillful teacher who introduced many �� Boulder undergraduates to the wonders of cell biology.

His broad knowledge of cell structure and the fundamentals of cell growth and differentiation allowed him to present that important material in an expert fashion. His humor, intelligence and interest in people made this task a pleasure, both for his many students and himself.

Staehelin’s research relied upon his expertise in electron microscopy and grew from his commitment to preparing cells for study with the most reliable methods available. He and his students wrote almost 300 scientific papers and book chapters, and he edited several books, earning him several prestigious awards and the admiration of his colleagues.

At the top of the page: Cells with nuclei in blue, energy factories in green and the actin cytoskeleton in red (ZEISS Microscopy/Flickr). Above: L. Andrew Staehelin was a long-time part of the Department of Molecular, Cellular and Developmental Biology.

Staehelin was born in Sydney, Australia, on Feb. 10, 1939, but his family soon moved to Switzerland, where he was reared and received his education, culminating in1966 with a PhD in natural sciences from the Swiss Federal Institute of Technology in Zurich.

He did postdoctoral work in New Zealand and then at Harvard with Keith Porter, a renowned electron microscopist. Staehelin and his wife, Margrit, moved to Boulder in 1970, where he joined the newly formed Department of MCDB. He was a proud member of that department until his retirement.

Staehelin was known as a stimulating and inspiring teacher who particularly enjoyed the challenges of teaching large courses, such as “Introduction to Molecular and Cellular Biology” and “Cell Biology.” The quality of his undergraduate teaching was recognized with two teaching awards.

His graduate teaching included contributions to the department’s core courses, but his greater graduate focus was on the students in his lab, where his many graduate students and postdoctoral fellows knew him as a rigorous perfectionist who demanded the attention to detail that is essential for high-quality science. Fortunately for all, Staehelin’s enthusiasm and optimism sustained the energy of those working with him.

Staehelin’s lifelong pursuit was the relationship between cell structure and function. His initial method of choice was freeze-fracture electron microscopy, which introduced him to the concept of rapid freezing for the preservation of cells in a good approximation to their native structure. His passion for improving “cryo” techniques culminated with the introduction of high-pressure freezing to the cell biological research community.

This technique has become the standard for studying the structure of cells at the nanoscale. During his final research years, he pushed this analysis into three dimensions by using electron tomography.

During his 36 years with �� Boulder, Staehelin took advantage of the sabbatical leave system to work at other universities, learning new experimental techniques and exploring new biological systems. His first sabbatical leave in Freiburg, Germany, was made possible by a Senior Humboldt Award. With support from a �� Faculty Fellowship, he took a sabbatical at his alma mater in Zurich, and for his final sabbatical he returned to Australia, to the University of Melbourne, as a visiting professor.

Staehelin’s awards and recognitions included membership in the German National Academy of Sciences Leopoldina, his becoming a fellow of the American Association for the Advancement of Science (AAAS), a faculty recognition award from �� Boulder, the Haselkorn Scholar Award from the University of Chicago, and appointment as a fellow of the Society of Plant Biologists.

His service to the research community included establishing the Plant Cell Wall Gordon Conference. Locally, Staehelin was known for his efforts to educate the public about genetically engineered plants, often writing newspaper op-ed pieces that helped to explain complex scientific concepts in simple, accessible language.

Because he recognized the need to increase food production, so the world could feed more people on less land and with less water, he championed the need to exploit the best plant-breeding techniques, including genetic engineering, as well as the best methods for cultivation.

Professor emeritus remembered for his ability to present important material expertly and for his humor, intelligence and interest in people

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