Each year, monarch butterflies embark on one of nature’s most astonishing migrations, traveling thousands of miles across North America. But in recent years, populations have suffered heavy losses. The decline of this beloved species has dominated conservation discussions, with campaigns urging people to take individual action —planting milkweed, creating butterfly gardens, and reducing pesticide use. But according to David Lohman, a professor of Biology at the CUNY Graduate Center and The City College of New York, focusing conservation efforts on a single butterfly species risks missing the larger crisis: the widespread decline of insect biodiversity worldwide.
The monarch’s migration path east of the Rockies faces challenges due to habitat loss, particularly the reduction of milkweed, and climate change. While the monarch’s migration phenomenon is indeed threatened, the species itself is not critically endangered, as it remains widespread and common throughout much of the world, Lohman says. He suggests that instead of concentrating conservation efforts on a single, well-known species, broader systemic changes — such as preserving wild habitats and reducing pesticides — would benefit not just monarchs but entire insect communities.

Conservation strategies for charismatic megafauna, such as tigers, pandas, and rhinos, often involve focused funding for breeding and maintaining reserves for individual species. But Lohman explains that insects require a different approach. This is in part due to insects’ unique reproductive strategies and ecological roles: Unlike birds or mammals, which invest heavily in raising a few offspring, most insects produce hundreds or thousands of eggs, of which only a fraction survive. This means that traditional conservation approaches, such as breeding programs or protected reserves for individual species, are less effective for insects. Instead, protecting the habitats that sustain these vast, interconnected populations is key.

“Insects have a capacity for rapid population growth, and their roles in the food chain are much different than that of other animals, not only in how they support the trophic pyramid but in their dietary specialization,” Lohman said. “Many animals are generalists that can eat a variety of foods, while insects are often highly specialized, consuming or parasitizing only one or a handful of species. This dependency of one organism on another makes habitat diversity incredibly important to all insect conservation. An insect population cannot survive without its specific hosts.”
Butterflies, like all insects, rely on diverse, stable environments to thrive. But habitat destruction, climate change, pesticides, and light pollution are severely reducing these supportive environments, contributing to what scientists are calling the “insect apocalypse.”

“It’s not one single thing leading to insect declines,” Lohman explains, “it’s a combination of many factors — essentially death by a thousand cuts.”

Insects’ public relations problem
Another overlooked challenge is the public’s perception of insect conservation. In a study Lohman co-authored, researchers found that people are far less interested in protecting insects than charismatic animals like pandas or elephants. Even among insects, public attention is skewed toward a few iconic species — like monarchs — while thousands of lesser-known but equally vital insects receive little concern. This bias, he argues, has serious implications for conservation funding and policy.

“Charismatic vertebrates like polar bears and elephants tend to captivate people, and unfortunately, insects don’t have as good of a PR machine, so they go unnoticed,” Lohman said. “It's hard to capture public interest for something so tiny and often nondescript.”
The way humans engage with insects also differs from interactions with larger fauna. Many people can recall raising monarch butterflies or ladybugs in a classroom, or catching fireflies in their backyards, fostering an appreciation for insects. However, these outdoor experiences are becoming less common for children today. Lohman argues that these experiences are critical for increasing public interest in insect conservation and provide unique hands-on engagement that isn’t often possible with other animals of conservation concern.

“To justify insect conservation, it is often pointed out that they provide many ecological services that directly benefit humans and are worth protecting,” Lohman said. “But for me personally, the reason why I think it's important to conserve insects is that they’re so damn fascinating. There are so many stories of unique biology, including morphology, diets, lifestyles, and adaptations, that really highlight the diversity of life. I specifically chose certain species with these fascinating traits to write vignettes about in my book, hoping others will appreciate this diversity as well.”
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Butterflies’ colorful lives and how to preserve them
Lohman’s research goes beyond conservation, exploring the ecology and evolution of insects, particularly butterflies, in the tropics of Africa and Asia to understand how species interact with each other and their environments. Recently, he co-authored The Lives of Butterflies: A Natural History of Our Planet’s Butterfly Life, which showcases the diversity of butterflies — not just in their coloration, but across their behaviors, life histories, and more.

“My hope is that the book has something for everyone, from amateur lepidopterists to experts who study butterflies like I do,” he said. “I’ve had colleagues tell me that they learned new things about species with unusual life histories reading my book, and I’m gratified that even people who have spent a good chunk of their life appreciating butterflies can still find something in the book that is new and interesting.”
Ultimately, Lohman’s perspective is a call to rethink how we approach insect conservation. Instead of asking how we can save the monarch butterfly, he urges people to ask how we can save the ecosystems that support all butterflies and countless other insects. By planting native plants, minimizing pesticide use, and advocating for policies that protect wild spaces, individuals can make a meaningful impact, he said.
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The future of butterflies, and indeed all insects, he argues in his book, depends not on isolated efforts to rescue individual species, but on a broader commitment to preserving the natural world.

Salmonella infections are a major public health issue in the United States, causing over 1.3 million illnesses annually. These infections are a leading cause of foodborne illness, often traced back to raw or undercooked poultry meat and eggs. Emerging antimicrobial resistance in Salmonella isolates found in retail chicken meat is a growing concern, the trends of which were recently explored in a new study by a group of researchers from the University of Illinois Urbana-Champaign.

Salmonella comprises thousands of strains, known as serovars, which vary in their prevalence, distribution, and antimicrobial resistance across different regions. Controlling Salmonella outbreaks can be challenging, as the pathogen is very diverse and some serovars are multi-drug resistant. Furthermore, infections in poultry often aren’t easy to detect.
“The problem in detection is that some Salmonella serovars don’t infect poultry, and in many cases, the chickens do not present as clinically ill,” said Csaba Varga (IGOH), an assistant professor of epidemiology specializing in the distribution and spread of diseases. “They can appear healthy while still harboring Salmonella, and then humans consume the meat and get infected.”

To monitor Salmonella's presence and antimicrobial resistance in retail chicken meat, the National Antimicrobial Resistance Monitoring System for Enteric Bacteria has been sampling chickens since 2002. Longitudinal datasets like these are invaluable for tracking changes in the bacteria over time, said Varga. In his recent study, he and his team utilized this extensive dataset to explore trends in the prevalence of the most common serovars of Salmonella and their antimicrobial resistance patterns over recent years.

The team includes Nasim Sohail, a visiting research scholar at the College of Veterinary Medicine, and Hamid Sodagari, a postdoctoral researcher in Varga’s lab, and first author on the study.

They examined publicly available data on nearly 40,000 samples taken from retail chicken meat between 2013 and 2020. Of these, approximately 3,000 samples (7.7%) tested positive for Salmonella. The four most common serovars identified were S. Kentucky, S. Typhimurium, S. Infantis, and S. Enteritidis. Notably, S. Kentucky was the most prevalent serovar in poultry, constituting about 35% of Salmonella-positive samples. However, Varga points out that it is of less concern because S. Kentucky rarely infects humans, unlike the other three serovars.

While the average prevalence of S. Kentucky and S. Enteritis has remained relatively stable over the years, the researchers observed a significant decline in S. Typhimurium and a dramatic increase in S. Infantis from 2013 to 2020.

“We were expecting to see a decrease in Typhimurium due to the live attenuated Typhimurium vaccine that the poultry industry has been using,” explained Varga. “But controlling for one serovar can open up the niche, allowing others to take over. We expected to see a potential increase in other serovars due to this, however, we didn’t expect such a dramatic increase from S. Infantis.”

Varga went on to explain that the prevalence of S. Infantis surged from around 3% of positive Salmonella samples in 2015 to nearly 40% in 2020. This is particularly concerning due to the high levels of antimicrobial resistance found among S. Infantis samples.

“S. Infantis has become increasingly prevalent and has recently emerged as multidrug-resistant due to a plasmid (pESI) within that serovar,” said Sohail. “This plasmid contains several antimicrobial resistance and virulence genes, that help with the pathogenesis of S. Infantis. This is likely why it is increasing in prevalence not only in the United States but also across the globe.”

The other serovars also demonstrated varying levels of antimicrobial resistance. Additionally, the four serovars varied in their spatial distribution across the United States, with high-proportion clusters of S. Typhimurium more commonly detected along the East Coast, and S. Kentucky along the West Coast and southern states.

Several factors could influence the distribution of Salmonella serovars, such as environmental differences or variations in chicken management practices. However, the researchers say more studies are needed to explore these factors in detail. 
The emergence of a multidrug-resistant S. Infantis serovar in the United States and worldwide is a significant public health concern. These findings underscore the need for further research and the implementation of serovar-specific mitigation strategies in the poultry production chain, said Varga.

“Our results show that the vaccination against S. Typhimurium is working, but that the industry will have a new challenge to control S. Infantis,” explained Varga. “They will likely need to figure out a different type of intervention since the current mitigation efforts are not working against it. This just shows we need to consider serovar-specific control measures for Salmonella in the future.”

The team plans to further investigate how management practices affect the development of antimicrobial resistance, and explore what can be done to reduce Salmonella prevalence and resistance to antimicrobials. Varga stresses that even with efforts to reduce Salmonella, it is unlikely to disappear anytime soon. Therefore, consumers should take safety precautions when handling and consuming poultry. 

“We can work to reduce Salmonella, but it won’t disappear,” said Varga. “Consumers need to be aware that they must take food safety precautions to cook poultry meat to temperature and not cross-contaminate food products in the kitchen.”
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The study is published in Food Control, found at https://doi.org/10.1016/j.foodcont.2024.110701. More information on other projects in the lab can be found at https://vetmed.illinois.edu/varga-lab/

Advances in genomics research and technology are providing a more comprehensive understanding of how our genetic code interacts with our environment to influence our health, behavior, and overall well-being. This has far-reaching implications for various fields, including healthcare, insurance, policing, and even judicial sentencing. The legal system faces the challenge of protecting individuals from potential misuse of genetic data, such as unfair denial of health insurance, while also allowing for the leveraging of its benefits, like improving early interventions for disease. Addressing these issues requires the judiciary to have a good understanding of genomics, ensuring that they can make informed decisions in cases involving genetic information.

To meet this growing need, the Carl R. Woese Institute for Genomic Biology at the University of Illinois Urbana-Champaign, in partnership with the National Courts and Sciences Institute, recently hosted the third "Genomics for Judges" workshop, which was held from June 27-28th. This workshop aimed to equip judges with the knowledge necessary to navigate the legal landscape shaped by advances in DNA sequencing, analysis, and more recently, artificial intelligence. The workshop was funded by the State Justice Institute.

The two-day workshop offered a comprehensive curriculum that included expert seminars and panels, interactive discussions, and hands-on experiments. Judges explored the latest developments in genomics and AI, increasing their understanding of its applications, implications, and limitations. By examining the intersection of genomics with the legal system, the event sought to prepare judges for the challenges and opportunities these technologies present.

The workshop featured many notable seminars, including one by Derek Hoiem, a professor of computer science, who provided an overview of AI. Hoiem differentiated between traditional narrow machine learning models and emerging generative AI technologies, like ChatGPT. He emphasized the importance of understanding AI's training processes, potential biases, and the role of digital forensics in verifying the authenticity of AI-generated media, a growing concern in legal contexts.

Another notable seminar was led by Brian Allan (IGOH), a professor of entomology, who discussed genetic modification in mosquitoes as a strategy to combat disease spread. He detailed current genetic modification techniques for tackling this, which include creating sterile mosquitoes or those resistant to diseases. Allan then highlighted the regulatory ambiguities surrounding genetically modified organisms and the legal questions judges might face in the future concerning the environmental and ethical implications of GMOs.

Alta Charo, the Warren P. Knowles Professor Emerita of Law and Bioethics at the University of Wisconsin-Madison, delivered a compelling keynote address on equity and access to emerging genome editing therapies. She reviewed recent advancements in genome editing, explaining the underlying mechanisms and the significant hurdles in making these therapies broadly accessible. Charo highlighted challenges such as financial barriers, the complexity of treatments, and the disparities in technological capabilities across different regions. She emphasized the critical role of the judiciary in ensuring that legal decisions regarding these technologies compel companies to address and devise solutions to these equity issues.

Additional seminars covered topics like diagnostics and classifications by AI models, using machine learning to predict health risks based on genomic data, and the future of human genetics in light of technological advances in genetic editing. These sessions underscored the transformative potential of genomics and AI in healthcare and emphasized the need for judicial understanding of these fields.

A highlight of the workshop was a hands-on experiment led by Dan Urban, IGB's Senior Outreach Activities Coordinator. Judges pipetted DNA samples from various commercially available snack foods into gels and used electrophoresis to separate the DNA, testing whether the snacks labeled as GMO-free actually contained GMOs. This experiment offered a practical demonstration of genetic testing techniques and their applications, and it quickly became a favorite among the judicial participants.

Case studies formed another critical part of the workshop, allowing judges to apply their newfound knowledge to hypothetical legal scenarios. In one hypothetical criminal case study, judges considered the legal processes involved in using AI to generate a suspect’s face from DNA evidence at a crime scene. They discussed the potential biases of such AI tools, the types of expert testimony required, and the ethical and legal ramifications of admitting AI-generated evidence in court. Another civil case study explored the idea of a lawsuit involving a genome editing tool used to cure an embryo of a life-threatening disease. In the hypothetical scenario presented, the child later develops cancer, and the parents believe it is related to genome editing. Judges examined the legal procedures for such a lawsuit, the necessary evidence, and the expert testimonies required to resolve the case.

The workshop, titled “AI in Genomics and Genetic Engineering” is part of the IGB’s Genomics forTM program, a series of workshops designed to educate different professional groups on genomics research, and explore with them its potential impact on the job sector they work in. 

“The Genomics for program is a prominent element of our efforts in outreach, and a vivid demonstration of our commitment to engage all sectors of the public with clear and trusted information on genomics,” said IGB director Gene Robinson. “We’re pleased and honored to again collaborate with the National Courts and Sciences Institute, one of the premier judicial training organizations in the country.” 
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The workshop underscored the critical role of education in bridging the gap between advancing technology and the judiciary. By equipping judges with a robust understanding of genomics and AI, the IGB aims to ensure that legal decisions involving these technologies are informed, fair, and just. 

Plants are diverse organisms capable of communication, self-defense, and forming cooperative partnerships with insects; yet these remarkable abilities are often overlooked in the bustle of everyday life. At Pollen Power summer camp, however, middle school students dive into this fascinating world of plant and pollinator interactions, bringing these hidden wonders to light.

Hosted by the Carl R. Woese Institute for Genomic Biology, Pollen Power has been transforming the way young minds see the world around them since its inception in 2013. The camp provides a dynamic learning environment filled with a blend of hands-on learning and scientific exploration, that encourages campers to see the world through the eyes of a scientist.

“At Pollen Power, students take something they consider an ‘ordinary everyday thing’ in nature and learn to see it in a new light,” said Sarah Choi, the IGB’s Outreach K-12 Project Manager and lead organizer of Pollen Power camp. “They start to appreciate the plants and pollinators around them. And through our activities and experiments they leave feeling like scientists, with more curiosity about the world around them.”

The camp, funded by the Center for Advanced Bioenergy and Bioproducts Innovation theme within the IGB and the Champaign Unit 4 School District, welcomed 4th-8th graders this year from June 3rd-7th. Throughout the week, campers engaged in various activities designed to teach them not only about plants and pollinators, but also teamwork, communication, and scientific observation.

In line with Pollen Power tradition, campers broke into small groups mentored by Franklin STEAM Academy staff, and designed and conducted week-long experiments to observe the growth rates of cress seeds under different conditions, such as varying liquids, temperatures, and light exposure. Predictably, seeds given water and sunlight flourished the most, offering practical insights into plant care and environmental factors.

Besides their experiments, the week’s itinerary was packed with diverse and engaging activities, featuring many exciting additions that were new to the camp this year. One highlight of this year's camp was the celebration of the simultaneous emergence of both the 13-year and 17-year cicadas, during which campers collected cicadas and learned the art of insect pinning. This hands-on activity connected the campers to a rare and spectacular natural event, enriching their appreciation of the insect world.

In addition, this year’s camp featured a new storytelling session with children’s author Janice Harrington, who read from her book Rooting for Plants. This session engaged the campers’ imaginations and helped to deepen their connection to plant life and their community. Another standout event was a talk by Todd Krone, co-founder and CEO of PowerPollen, a company innovating in the field of pollen collection and preservation for agriculture. Krone's presentation on pollen biology was followed by an interactive activity, giving campers a glimpse into the exciting applications of pollen science in modern agriculture.

The IGB’s new mobile lab bus also made its debut at Pollen Power. Using the bus's advanced equipment, campers were able to examine and image plants and insect specimens they had collected from a nearby prairie. Campers also toured Prairie Fruit Farms, where they experienced firsthand how local agriculture integrates with natural ecosystems. The farm features goat pastures, organic fruit orchards, and restored prairie, emphasizing the connection between plants, pollinators, and sustainable farming practices.

Throughout the week, the campers explored state-of-the-art facilities in the IGB Core, where they used confocal microscopes and 3D imaging to visualize different pollen particles and reconstruct plant images. They also crafted art from the plants they gathered, creating watercolor paintings with chlorophyll dye they had extracted, and transferring the colors of petals and leaves onto bandanas through hammering.
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By the end of the camp, it was evident that campers had gained a profound appreciation for the plants and pollinators in their environment. Through activities, tours, and expert interactions, Pollen Power provides a rich and varied learning experience that aims to inspire the next generation of scientists.

Rapid tests for COVID-19 have become a gold standard for virus testing, widely available at pharmacy chains and drug stores due to their low cost, speed, and ease of use. However, these tests often fall short in accuracy compared to molecular tests like PCR, especially in the early stages of infection. Recently, researchers at the University of Illinois Urbana-Champaign developed a new rapid test that is more reliable and sensitive than commercial tests, by using DNA nanotechnology instead of antibodies to detect the SARS-CoV-2 virus.

Commercial rapid tests for SARS-CoV-2 either the presence of antigens—proteins found on the virus—or antibodies produced by our immune systems in response to infection. While effective when a patient’s infection is well-established, these tests can produce false negatives if conducted too early, when virus levels are low, and the body has not yet mounted a significant immune response. Additionally, prior infection can sometimes trigger a false positive due to lingering antibodies.

The new test, developed by the Illinois team, utilizes DNA nanostructures called DNA nets, specifically designed to bind to the spike proteins on the virus. In a positive sample, the DNA net captures the virus and moves along a test strip, akin to commercial tests. When the virus reaches the test line, which also contains DNA nets, it becomes completely bound. Gold nanoshells intermixed with the nets amplify detection, lighting up to form a bright, easily visible line, indicating a positive COVID-19 result. 

“We took advantage of the large amount of research advances that came out of COVID-19.” said Saurabh Umrao, first author on the study and postdoctoral researcher in the lab of Xing Wang (CGD), a bioengineering faculty. “One being DNA aptamers, which are synthetic DNA molecules that you can design so that they are very specific to a single target. When these are added to the DNA nets, it’s like using a fishing net to catch a specific fish; in this case we’re capturing the whole virus.”

Umrao notes that the new test works on multiple strains of SARS-CoV-2 and is 100 times more sensitive than currently available rapid tests, enabling detection of viral loads as low as 103 viral copies/mL, compared to the 105 viral copies/mL needed for standard commercial tests. Furthermore, by modifying the DNA aptamers in the nets, the tests can be tailored to detect other kinds of viruses as well, Umrao said.

“We’ve been applying for grants to generate funds for clinical trials,” said Umrao. “We want to use actual patient samples and show that this technology can be used not only for early detection of COVID-19, but for other concerning diseases respiratory diseases, as well as blood-borne diseases like HIV.” 

The team has secured intellectual property for this new technology and is refining the test to enhance its portability and ease of use, said Umrao. They also plan to add another test line to the strip that will show if a patient has influenza as well. 

“It is important for people to be able to distinguish whether they have influenza or SARS-CoV-2 to receive the appropriate antiviral therapy,” said Umrao. “But the symptoms for these two diseases are nearly identical. That’s why we plan to add another test line to help people determine which they are infected with.” 

Umrao explained that this innovative testing approach aims to make rapid tests more reliable, enabling early and accurate detection of COVID-19 and other infectious diseases. This can help manage and control the spread of infections, improving healthcare outcomes for individuals and communities worldwide.
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The study is published in Analytical Chemistry, and was funded by the National Institute on Alcohol Abuse and Alcoholism, and the National Institute of Dental and Craniofacial Research. The paper can be found at https://doi.org/10.1021/acs.analchem.3c03698

We often think of species as separate and distinct, but sometimes they can interbreed and create hybrids. When this happens consistently in a specific area, it forms what’s known as a hybrid zone. These zones can be highly dynamic or remarkably stable, and studying them can reveal key insights into how species boundaries evolve—or sometimes blur. In a new study published in Evolution, researchers at the University of Illinois Urbana-Champaign describe a hybrid zone between two manakin species in Panama that has overall remained relatively stable over the past 30 years.

Hybrids resulting from mixed-species breeding are not uncommon; consider, for example, the mule (horse-donkey) or the liger (lion-tiger). However, many of these classic examples of hybrids are typically infertile and exist only as first-generation crosses. In contrast, along the western edge of Panama, against the Caribbean Sea, a long-term hybrid zone exists between two species of birds, the golden-collared manakin and the white-collared manakin.

Previous research conducted nearly 30 years ago on this hybrid zone found that the genomic center—where the population’s genome is nearly 50% white-collared DNA and 50% golden-collared DNA—did not overlap with the phenotypic transition zone, the area where the population visually transitions from more golden-collared plumage to more white-collared. The previous study found these two areas were about 60 km apart, and until recently, it was unclear whether there had been any changes over the years.

Kira Long, a former graduate student in Jeff Brawn’s lab, now a postdoctoral researcher at the University of Idaho, and her team decided to compare the current population of manakins in the hybrid zone to those from the previous study ~30 years ago. Doing so would allow the researchers to see whether the genomic center or the phenotypic transition zone has moved over time, and how stable the genomic and phenotypic traits are across the population.

“Currently, hybrids at the genomic center look phenotypically almost identical to the golden-collared manakins,” explained Long. “They have the golden yellow collar and dark green belly of golden-collared manakins. What’s crazy is that these hybrids are the most genetically mixed between white and golden-collared manakins, yet they look almost identical to the golden-collared parents. Whereas the birds that visually look the most mixed have genetically a majority of white-collared DNA.”

Long’s team includes Illinois researchers Jeff Brawn, a professor emeritus of natural resources and environmental sciences, Julian Catchen (CIS/GNDP), an associate professor of integrative biology, and his former graduate student Angel Rivera-Colón, as well as collaborators from the University of Maryland College Park and the Smithsonian Institution.   
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Over four years, the team captured and took blood samples from over 600 manakins across different areas of the hybrid zone. The blood samples were sequenced using RADseq to examine thousands of genomic markers across the genome. These were then compared to samples taken from museum specimens housed at the Smithsonian Institution that were used in the original, older study. The team also measured phenotypic traits of the wild-caught and historical birds, known to differ between golden-collared and white-collared manakins, including feather coloration and length.

After comparing the historical and wild-caught bird genomes, the researchers found that the genomic center of the population had not moved in approximately 30 years. Less than 3% of the genomic markers tested had changed over time. Furthermore, the phenotypic transition zone had also remained stable, with only one trait—belly color—having shifted in location over time by about 10 km. 

“What this means is that if you went to the same location in the phenotypic transition of the hybrid zone 30 years ago, you would see birds with more yellow bellies, whereas if you went to that same spot now you would see birds with more olive-colored bellies,” said Long. “The hybrid bellies are essentially getting darker over time. This may mean that there is some sort of selection for the green bellies in these populations where it is spreading.”

Hybrids have varying success in the animal kingdom depending on the species that are mixed. There is a hybrid zone of cottonwood trees, for example, that is extremely stable, only moving slowly during interglacial periods, according to Long. Hybrids of many species often have less fitness than the parental species because they are too intermediate in their traits, but sometimes hybrids are able to capitalize on this and find success, by making use of environmental niches that are between the optimums for the parental species.

According to Long, the population of hybrid manakins seem to be doing just fine, which may explain why the hybrid zone is so stable. While there is evidence of decreased hatching success in the hybrids—which Long says will be published soon in her next article—she notes that this is essentially nature filtering out the genetic combinations between the white-collared and golden-collared manakins that do not work. Once they hatch, the hybrids’ survival appears similar to the parental species, and they do not seem to have issues finding mates, according to Long.

The next big steps for this system is to determine if female choice is affecting selection for specific hybrid phenotypes and determine the underlying genomic architecture of these traits, Long said. This may provide insight into why hybrids typically resemble the golden-collared species and why the transition zone for belly color is shifting while other phenotypic traits remain relatively stable among hybrids. 

“It’s thought the females prefer golden-collared colors, and that might be why the more olive belly color, which is a trait of golden-collared manakins, is spreading in the hybrids,” said Long. “We have indirect evidence for this, but it’s never been formally tested, so it would be great to get that last piece of the puzzle.”
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The study was funded by the NSF, USDA, the Smithsonian Institution and the National Museum of Natural History. The paper can be found at https://doi.org/10.1093/evolut/qpae076

The NSF Molecule Maker Lab Institute, hosted by the University of Illinois Urbana-Champaign, is a cutting-edge research institute focused on advancing the creation and study of molecules using AI and machine learning. Researchers at the institute combine expertise in chemistry and biology with advanced tools to accelerate the discovery and manufacturing of important molecules, such as those used in therapeutic drugs. Recently, MMLI unveiled two new tools and a significant upgrade to an existing tool in the AlphaSynthesis suite, further enhancing researchers’ ability to synthesize functional molecules.

AlphaSynthesis is an MMLI platform offering click-and-go tools with a user-friendly interface, aimed at integrating knowledge of molecules and molecular synthesis across publicly available databases and publications. The suite currently includes two AI tools developed over the four years since the institute’s inception: Contrastive Learning enabled Enzyme ANnotation (CLEAN), which can accurately predict enzyme function based on amino acid sequences, and ChemScraper, which can extract chemical structures of molecules from publication texts. The suite also includes Molli, an online tool for creating catalysts and extracting features from molecules.

“A key deliverable of the institute is to develop new AI tools that enable highly efficient discovery and synthesis of important molecules,” said Huimin Zhao (BSD leader/CABBI/CGD/MMG), Steven L. Miller Chair of Chemical and Biomolecular Engineering and Director of MMLI. “We’ve designed a variety of AI tools in the AlphaSynthesis suite as an end-to-end pipeline for molecular discovery and synthesis.”

Among the newly announced AI tools is NovoStoic, which uses a computational procedure to plan enzymatic synthesis routes for creating a target molecule. Many molecules of interest are derived from microorganisms that have enzymes or gene clusters necessary for their creation. NovoStoic leverages this by determining the specific biochemical steps needed to generate the desired molecule using enzymes or microbes, optimizing the process, said Zhao.

Another new tool is Somn, which uses a machine learning model to optimize chemical reactions, by improving catalysts and predicting the best conditions for the desired reactions to occur. Zhao explained the model specifically predicts the appropriate ligands, solvents, and bases that are needed for creating target molecular reactions.

The new suite also includes updates to Chemscraper. Now the AI tool not only extracts and creates chemical structures from text, such as articles or books, but it can also mine the literature for figures of chemical diagrams. Zhao explained that the tool can also create 3D chemical structures based on these images, allowing researchers to visualize the details of the structures.
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These advancements mark a significant leap forward in the field of molecular innovation, making it easier and faster for researchers to develop new molecules. As MMLI continues to push the boundaries of molecular science, the potential for new discoveries and applications expands, benefiting various fields from medicine to materials science.

What do marine ecosystems, worm regeneration, and a soccer-themed video game have in common? On the surface, perhaps nothing, but these are some of the fascinating projects middle schoolers pursued as part of the STEAM TRAIN program this year. The STEAM (Science, Technology, Engineering, Arts, and Mathematics) TRAIN (Transdisciplinary Research Across Institutional Near-peers) program is a collaboration between the Carl R. Woese Institute for Genomic Biology, Franklin STEAM Academy, and Uni High, that encourages middle school students to explore any science or engineering projects that interest them, with no limits other than their own creativity (and feasibility, of course).

STEAM TRAIN is organized by IGB’s Senior Outreach Activities Coordinator Daniel Urban and Franklin’s Magnet Site Coordinator Zanne Newman, and funded by the University of Illinois’ Community Research Partnership Program. The program runs from September to May every year, and has just completed its fourth successful year, engaging over 20 middle school students.

The program provides mentorship across multiple levels, including Uni High students, and graduate students and professors from the IGB. With guidance from their near-peer mentors, middle schoolers learn to formulate hypotheses, refine their research questions, collaborate effectively, and take the lead on their investigations. The program empowers student-driven research, giving middle school students the opportunity to conceive and design their own scientific and engineering projects. Mentors play a crucial role in steering the project design and equipping students with the tools needed to realize their innovative ideas.

Middle schoolers then use these tools to develop their group’s science projects over the course of the year. This year five groups presented the culmination of their projects in May, which delved into a range of disciplines including biology, engineering, and computer science.

Some groups researched the ecology of different animals, with one focusing on habitats, diets, and potential threats to various marine species, and another examining the different locomotions of snakes and the environments those movements are used in. Another group instead explored computer science, coding a Pong-like video game using Python, where two players compete to push a ball into the opposing goal to score points.

One group, fascinated by the regenerative abilities of planaria flatworms due to their stem cells, conducted an experiment in which worms were bisected and observed for regrowth. They found that whether a worm was cut into two or four pieces, all segments regrew into whole, separate individuals within five weeks, noting that previous research has shown that even a 1/200th piece of worm can regenerate.

Another group took an engineering approach, deciding to test the tensile strength of different materials, including wood, plywood, cloth, silk, and various metals. Materials were clamped between tables, and a bucket was hung from them and filled with weight until the material broke or became severely warped. Brass, wood, and silk proved to be among the strongest materials in the tensile test. The group also tested the durability of different materials under a blowtorch (operated by an adult, of course) or when submerged underwater for prolonged periods.

"I am always impressed by the types of questions our students ask,” said Danny Ryerson, IGB’s Outreach Activities Coordinator. "They choose incredibly interesting and challenging topics to research, and the levels of excitement and ingenuity they tackle these problems with are amazing."
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The STEAM TRAIN program exemplifies the power of creativity and mentorship in inspiring the next generation of scientists and engineers, showing that with guidance and resources, young minds can achieve extraordinary things.

CRISPR, (short for “clustered regularly interspaced short palindromic repeats”), is a groundbreaking gene-editing tool that empowers scientists to finely manipulate DNA, whether by inserting, deleting, or swapping genetic materials. This technology harnesses programmable enzymes, acting as molecular scissors, to precisely cut DNA at targeted locations. Among these enzymes, Cas12a stands out for its specificity and accuracy in its genome editing capabilities compared to the more widely used Cas9 enzyme. However, Cas12a's efficiency in making these edits currently falls way short of Cas9.

In a recent study published in Nature Communications, researchers at the University of Illinois Urbana-Champaign unveiled a novel strategy to bolster Cas12a's activity while preserving its accuracy. Led by Huimin Zhao (BSD theme leader/CABBI/CGD/MMG), Steven L. Miller Chair of chemical and biomolecular engineering, the team included graduate students Guanhua Xun and Zhixin Zhu, postdoctoral researcher Jingxia Lu, and automation engineer Nilmani Singh from the Carl R. Woese Institute for Genomic Biology.

CRISPR relies on programmable editing enzymes called nucleases, sourced from microorganisms like bacteria and viruses, to cut DNA. These enzymes, which include Cas12a and Cas9, are guided to their DNA targets by CRISPR RNA. Cas12a exhibits superior accuracy, displaying fewer off-target effects compared to Cas9, as well as the ability to edit multiple genome locations simultaneously. Yet Cas12a’s high accuracy is a double-edged sword, as it can hinder its genome editing activity.

“The human genome is large, around 3 billion base pairs. But if you just want to hit a specific 20 base pairs, there’s a high chance you won’t hit just that,” explained Singh. “That’s a big hurdle. CRISPR offers lot of potential for drug development, but these won’t make it to clinical trials unless you minimize off-target effects.”

Prior efforts by other researchers to enhance Cas12a's efficiency involved tinkering with the enzyme itself, but the Illinois team took a different approach, focusing on the guide crRNA instead.

The researchers incorporated 2-aminoadenine, also known as base Z, into the structure of the crRNA. This alteration fundamentally transforms the base pairing dynamics through the substitution of base adenine for base Z. The resulting Z – thymine bond is stronger due to the three-hydrogen bonds, increasing the binding efficiency of crRNA to the target DNA. This, in turn, enhances Cas12a's activity while maintaining its specificity, rivaling the efficiency of Cas9 in mammalian cells.

“Our guide RNA engineering is very unique, because we incorporate a natural occurring, non-conical base,” said Zhao. “When we think of DNA we think of the typical ATCG bases, but a few years ago we discovered some organisms have base Z instead of an A in their genome. Ever since then we’ve been building off that discovery, exploring new applications for this.”

The team says this new approach has many implications for therapeutics, cell engineering, and in-vitro diagnostics, as it addresses a significant hurdle in gene editing efficiency. In fact, the team had previously used this strategy to integrate base Z into mRNA used in the COVID-19 vaccine, substantially bolstering antigen-specific immune responses. Xun explained that base Z holds promise for vaccine development due to its ability to decrease immunogenicity, or the bodies incorrect immune response to antibodies, of the vaccine.

“Compared to protein engineering strategies which alter the Cas nuclease, our strategy is very simple,” said Xun, who is first author on the study. “We showed previously that this strategy was effective in creating a Z-based COVID-19 vaccine, and we think it has many more potential uses across both academia and industry.”

“It was surprising to me how such simple engineering could lead to a huge improvement in efficiency,” said Zhu. “Other methods like protein engineering require many rounds of screening, but with our method we can move the process along faster.”

CRISPR technology has countless potential applications, from treating genetic diseases, to creating genetically modified organisms, to advancing biomedical research. Its ease of use, precision, and versatility have made it one of the most powerful tools in modern biotechnology. By extending this strategy to other genome editing tools, the team envisions more efficient targeting of disease-associated genes, fostering new frontiers in precision medicine.
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The study was funded by the NIH and the Steve L. Miller Endowed Chair fund. The paper can be found at https://doi.org/10.1038/s41467-024-48012-x

Decoding decisions of parental stickleback fish
Growing up in upstate New York, Tina Barbasch spent countless hours catching salamanders and frogs in her backyard woods. Although her initial dream was to become a veterinarian, a suggestion from a friend’s mother, who was a biologist, steered her towards a career in research. Reflecting on her upbringing, she credits her father, a mathematics professor at Cornell, for showing her that "research was a real profession that people could have.”

Barbasch pursued her undergraduate studies at Cornell, majoring in Biology. It was there that her interest in behavioral studies blossomed, particularly through working on a project with local spotted salamanders. This passion led her to Boston University, where she earned a PhD in marine ecology and animal behavior under the guidance of Peter Buston. Her doctoral research delved into social behaviors and parental care in clownfish.

“Clownfish behavior is fascinating. They live in these social groups, they can undergo sex changes, and the male and female share the duties of parental care,” Barbasch said. “I was originally very behavior-focused, but as time went on, I started thinking about mechanisms, because they really shape how behavioral responses occur, and they can facilitate evolutionary change.”

Now a postdoctoral researcher at the IGB, Barbasch has refined her focus on social decision-making in animals, integrating behavioral work with genetic analyses. Under the mentorship of Allison Bell (GNDP leader), a professor of integrative biology, Barbasch investigates how animals navigate various sources of information to make decisions, particularly in the context of parental care. Her primary study subjects are threespined stickleback fish.

“Sticklebacks are really charismatic study organisms,” explained Barbasch. “The males build nests and provide all of the parental care to the eggs, fanning them and defending them from predators. And they also care for the fry after they hatch. They're doing lots of behaviors all at once, and I wanted to understand the mechanisms in the brain underlying how they respond to these multiple competing demands.”

Barbasch employs a blend of lab and field experiments to explore her questions. Her experiments often involve exposing fish to multiple stimuli simultaneously to observe their choices. This could range from territorial challenges, to mating opportunities, to predation risks. She examines what breeding males prioritize when faced with these multiple challenges, and then analyzes the gene expression in their brains to see how this relates to the observed behaviors.

Thus far, she has found that stickleback males make compromises in response to tradeoffs in different social situations, with individual variations in decision-making strategies. She has also identified a set of genes activated in the brain when males face behavioral tradeoffs.

“I found there’s a ton of individual variation in how they can manage these competing demands,” said Barbasch. “I want to further explore how these genes contribute to individual variation, and if that makes some males better at decision making than others. If this set of genes harbors genetic variation, then it can be a target for selection.”

In her most recent experiment, Barbasch journeyed to Alaska to study how wild sticklebacks juggle tradeoffs between feeding and parental care. Sticklebacks in Alaska exhibit varied foraging niches, with some foraging in shallow water and others in the deeper water of lakes. However, since they all nest within the shallow waters, this prompted questions about their parenting and feeding tradeoffs.

Barbasch presented the wild males with a feeding opportunity near their nests, observed their behavior, and collected them for gene expression and neural activity analysis, which she is currently analyzing. When asked about the challenges of working in Alaska, she noted that swarms of mosquitoes and cold waters were surprisingly not the most daunting aspects.

“When you're snorkeling in Alaska, you need to wear a dry suit to keep you warm,” explained Barbasch. “But it's almost impossible to get all the air out of the suit, and then when you get in the water, you're just this big floating balloon. So, the challenge is not so much swimming, but rather trying to approach these fish as a terrifying human balloon without freaking them out.”

As she aspires to continue her career in academia, Barbasch is currently applying to faculty positions at various universities, though she says she would be open to anything that allows her to “get out there and be with nature and animals.”

Outside of her research, Barbasch enjoys fly fishing, a hobby she picked up during graduate school. “I believe it’s important to have something to turn off your brain, and for me, that’s fly fishing. Artificial lures called flies are used to trick a fish into thinking that it's an insect or something tasty. It’s very appealing to me because every time I catch one I get that satisfaction of knowing that I tricked the fish based off of their ecology.”

Barbasch says the irony of fishing to get a break from researching fish was not lost on her, but did remark that “fly fishing gets me thinking about fish in a very different way. I learn what fish are in different rivers, and what attracts them. Some fish are very picky, and sometimes your fly needs to look like a specific insect that's hatching out at that particular moment.”

Apart from fishing, she loves spending time with her supportive husband, Alex. “It’s nice to have someone outside of academia that you can go home to and get new perspectives from. Someone that can ground you and help you think outside the box,” said Barbasch.

While research can often be a rocky road of trial and error, Barbasch says she navigates this road by embracing the wisdom encapsulated in a quote by Radhakrishnan Pillai that her grandfather often cited.
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“There are three types of people in the world. The first type learns by making mistakes; the second type keeps making mistakes but never learns; and finally, the third is the most intelligent type – they learn from the mistakes of others.”

Biomarkers are small molecules of interest to researchers, because they can indicate underlying diseases, often even before symptoms even appear. However, detecting these markers can be challenging as they are often present in very low quantities, especially in the early stages of a disease. Traditional detection methods, while effective, usually require expensive components like prisms, metal films, or optical objectives.

In a recent paper published in Applied Physics Letters, researchers at the University of Illinois Urbana-Champaign have unveiled a novel approach to detecting low concentrations of biomarkers that paves the way for biodetection technology that is simple to use, highly sensitive, and surprisingly affordable.

“The goal of this technology is early diagnostics, to be able to detect molecules associated with diseases at very low concentrations, sometimes a few molecules per millions, very early on,” said Seemesh Bhaskar, a postdoctoral researcher in the Cunningham lab and first author on the study. “Looking for very small concentrations of micro-RNA, circulating tumor DNA, and exosomes, for example, can help determine whether a patient will develop cancer one or two years down the line.”

Early detection of biomarkers is crucial for predicting and managing diseases effectively. There are many strategies for measuring the presence and concentration of biomarkers, but a common approach involves binding them with a fluorescent molecule, called a fluorophore, which emits fluorescence when excited with light.

Bhaskar noted that while there are technologies adept at detecting these low levels of fluorescent biomarkers, they are often bulky and expensive, limiting their accessibility in healthcare, particularly in resource-limited areas.

The approach encompasses a novel phenomenon for detecting light, called radiating guided mode resonance, which utilizes photonic crystals — thin pieces of glass with small gratings on the surface. These gratings help direct the photons, which are small particles of light, emitted from biomarkers along a pathway via a steering effect. This pathway is “tuned” to match the wavelength of the fluorescence emitted by the biomarkers, optimizing light collection and enhancing detection sensitivity.

Bhaskar likens this to a rhythmic dance of light energy within the crystal, where light is amplified while taking on the properties of the photonic crystal. One property of the crystal, called polarization selection, equalizes the polarization of the light, making for clearer and sharper detection of fluorescence. Together, this can result in an output that is 100 times stronger.

“To me, this is a whole new way of looking into the properties of light itself,” said Bhaskar. “The photons adapt, change, and evolve as they pass through the photonic crystal. The light picks up new characteristics without losing its essence. It's a testament to the adaptability and transformative power of light.”

Discovery of this new phenomenon sets the stage for future detection platforms that will be able to detect molecules at picomolar levels without relying on costly components, making biodetection technology more sensitive, accessible, and affordable.

While radiating guided mode resonance can theoretically be used to enhance detection of many different biomarkers, the Cunningham lab is particularly interested in early cancer detection. The new phenomenon holds promise for affordable technology that will be critical for populations in resource-limited settings, where early disease detection and treatment can make a profound difference.

One of the lab’s long-term goals after development of this technology is to make it compatible with smartphones, further enhancing its accessibility. The envisioned future product would be a simple fixture attached to a smartphone’s camera, allowing a photonic crystal to illuminate a test sample while the phone’s camera measures the fluorescence emission.
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“We are creating biosensing systems that are extremely sensitive while utilizing simple and inexpensive detection instruments,” said Brian Cunningham (CGD leader/MMG), a professor of electrical and computer engineering and program leader at the Cancer Center at Illinois. “This is what creates a path toward sophisticated health diagnostics making their way to our health clinics, farms, and homes.”

The study was funded by NIH, NSF, and the Cancer Center at Illinois. The paper can be found at https://doi.org/10.1063/5.0203999

In coastal arid regions where water sources are scarce, windborne fog droplets play a crucial role in sustaining life. Many plants collect droplets from the fog, serving as a vital water source for various organisms, but a few beetle species have evolved their own unique strategy for water collection - utilizing their bodies to intercept the droplets. However, the mechanics behind this process have long puzzled researchers due to the beetles' bulky morphology. In a recent study published in PNAS Nexus, scientists delved into how adaptations in the beetles' back enable them to gather enough water.

Two species of Namib desert beetles make use of a behavior called fog basketing to collect water droplets from the morning fog. They ascend dunes and balance on their front appendages, leaning their bodies into the wind. Microscopic droplets from the fog accumulate on the beetle’s back, and then trickle towards its mouth. Given that slender structures, akin to those observed in plants and human-made meshes used in arid regions, are best for fog droplet collection, questions arose regarding the feasibility of water collection with the beetles' morphology.

“In terms of fluid dynamics, water collection efficiency is way higher with thin structures like a mesh,” explained Hunter King, an assistant professor of physics at Rutgers University. “But if you’re a beetle, you’ve got a ball shaped body, and you don't have the freedom to change your geometry that wildly. We wanted to determine the strategy they use for a situation that's not ideal to begin with.”

The experiment comprised two main components: a computational phase and an experimental phase. The computation segment, led by Mattia Gazzola (M-CELS), an associate professor of mechanical science and engineering at the University of Illinois Urbana-Champaign, involved the creation of models to assess the impact of various surface geometric features on water collection. Utilizing data from these simulations, they then produced 3D printed models replicating different curvatures and surface properties derived from the models.

In the experimental phase, led by King, these 3D printed models, alongside deceased beetles, were employed to gauge their water collection capacity. The researchers constructed miniature tunnels to channel fog, where the models and beetles were individually placed at the tunnel's end connected to a sensitive load-bearing measure. This apparatus measured how much water accumulated on the target’s surface.

In addition to altering the 3D printed targets, the scientists manipulated the surface features and wettability (how hydrophobic or hydrophilic something is) of the beetles to investigate its effect on water accumulation. Given that the beetles' backs are inherently hydrophobic, the researchers coated beetles with a nanoscale-thin layer of gold to render them hydrophilic. To eliminate surface irregularities, an intriguing method was employed: applying nail polish to smooth out the beetle's backs. Some beetles received only gold or nail polish, while others were coated in both.

“We wanted to change the geometry of the beetles without changing the wettability, and the student working on this came up the elegant solution to use nail polish,” said King. “Just as nail polish makes a perfect layer, smoothing out all the details on a nail, it worked the same way for the beetles.”

They found that in both the 3D models and the beetles, surface bumps and a textured surface resulted in the most water accumulation. Similar to rain droplets colliding with the pavement, Gazzola explained that water particles that collide with a flat surface tend to be mostly deflected away. However, the introduction of bumps and slopes alters the trajectory of the colliding water, facilitating increased water retention.

“We show in our designs that if you add bumps on the back, resulting in these very sharp deflections in the back’s curvature, the water particles hit the bump, but then the flow continues to move along the back,” explained Gazzola. “And then it continues to flow over another bump and another, and the space between bumps then serve as traps to collect the water.”

Surprisingly, the researchers discovered that the wettability of the beetles did not substantially influence water collection; instead, only geometric features played a significant role. However, the researchers did observe that wettability influenced the directional movement of water down the beetle's back, supporting previous research underscoring the importance of wettability in guiding water towards the beetle’s mouth.

“Cumulatively from a very smooth surface, we found that adding microscopic geometric features plus a roughness on the surface gives you about a 400% increase in water collection,” said Gazzola. “Now this is still a very small amount of water, but the beetle is also very small, so it’s enough water for its needs.”

The team says these findings likely won’t be applicable for collecting water on the scale that humans need, but the results could inform material designs for when the opposite pattern is desired – avoiding water accumulation.

“We show that by changing the texture of something that wouldn't otherwise have caught very much moisture, now it’s collecting more,” said King. “This is great from the beetle’s perspective, but this same effect could be disastrous if you don't want to collect droplets on something. There are aerodynamic elements for wind turbines or planes that involve changing the surface morphology so that drag is reduced, but that same thing might cause icing to be a much bigger issue.”

This experiment offers a biological insight into how the beetles, despite their shape, manage to gather enough droplets by fog basketing. Moving forward, the team intends to delve further into the adaptations of organisms with diverse masses and shapes in managing water and heat exchange.
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This study was funded by NSF, and can be found online at https://doi.org/10.1093/pnasnexus/pgae077

Scientists have long pondered the beginnings of life on Earth. One theory is that RNA, which is ubiquitous across all domains of life, played a central role in early life. Similar to DNA, RNA possesses the ability to store genetic information. However, to initiate life's processes, early RNA must have also possessed the capability to self-replicate and catalyze biochemical reactions independently, without the assistance of specialized enzymes.

Previously, it was unclear how a molecule this complex could arise without any precursors. However, in a new study published in eLife, Alexei Tkachenko, a physicist at Brookhaven National Laboratory, and Sergei Maslov (CAIM co-leader/CABBI), a professor of bioengineering and physics at the University of Illinois Urbana-Champaign, describe their model that demonstrates how such a molecule could gain functionality.

“RNA is very preserved across all organisms. So, it’s like a smoking gun that RNA has a central point in life,” explained Tkachenko. “The problem is that modern RNA is very finely tuned and complex, so we wanted to see how life might emerge from something much simpler.”

While modern RNA relies on enzymes for replication and catalytic activity, the origins of these enzymes themselves remain a puzzle. However, the discovery of ribozymes, RNA molecules exhibiting enzymatic properties, suggests a plausible pathway for the emergence of early functional polymers.

The challenge lies in understanding how these ancient RNA molecules could have possessed the ability to "cut" other molecules, a crucial step in the replication process of DNA and RNA.

“Experiments have shown that a cleavage ribozyme, which relies on only a handful of conserved bases to do its job, can emerge spontaneously with no prior information, if the experimenter artificially selects for things that cut other things,” said Tkachenko. “The problem is that it's not clear how evolution would select for something that cuts things, essentially selecting for a destructive enzyme.”

To tackle this question, the researchers devised a model simulating basic RNA molecules devoid of enzymatic activity. Within this model, random bond breakage was allowed to occur, mimicking real-world chemical processes. The researchers observed that breakage led to more copies of the polymer that was broken, meaning that molecules capable of self-cleavage would have been favored by evolution due to their ability to replicate.

Maslov illustrated this concept with an analogy, likening the process to cutting an earthworm in half, where both halves regenerate into whole organisms.

“In principle, if you wanted to make many earthworms from one earthworm, you would just start cutting them one by one,” explained Maslov. “The same idea is why cutting would be selected for in RNA, because when it’s cut it regrows itself from individual building blocks. And that was the connection, to explain why the first ribozyme was selected to cut things — because cutting is how RNA exponentially grows.”

But how does catalytic activity arise from such simple beginnings? In a second model, the researchers demonstrated how RNA molecules could evolve into complex ecosystems with functional properties, where different polymers in these ecosystems cleave and replicate each other.

Their model simulated a pool of polymer chains competing for nucleotide "building blocks", and cutting other polymers they encountered. Polymer chains pair in specific ways (such as the A-T nucleotide pairing in modern DNA), and as such, the chains in the simulation formed template and complimentary strands, essentially working together.

“Pairing rules are the basis for how information is preserved and propagated in the future,” said Maslov. “And it’s also important for function, because it gives way to hairpins in the strands that lead to a three-dimensional shape, and these are the ones which are capable of enzymatic activity.”

Polymer replication in the model occurred based on temperature being cycled between hot and cold phases (typical in day-night cycles), suggesting that ancient polymers may have relied on such cycles to grow. Nonorganic surfaces such as rocks may have also facilitated this process.

These findings offer compelling insights into the natural emergence and selection of ribozymes with enzymatic activity, shedding light on a crucial aspect of early life evolution. The researchers advocate for experimental validation of their models to confirm their predictions.

Additionally, they acknowledge the discrepancy between bidirectional growth in their model and the unidirectional growth observed in DNA and RNA replication in real life. Alexei says they plan to continue adjusting the model to see if they can find variations which would result in unidirectional growth.

“It is not a coincidence that Carl Woese, who our genomic institute is named after, used pieces of ribosomal RNA to make his trees of life,” said Maslov. “RNA inside ribosomes is universal to every single organism from bacteria to archaea to eukaryotes like you and me. This paper definitely doesn't solve the problem of origin of life, but it fills a tiny gap in our understanding of how early RNA may have functioned to bring about life.”
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This study was partially funded by U.S. Department of Energy Office of Science and can be found at https://doi.org/10.7554/eLife.91397.3

Living organisms produce a diverse suite of natural products which can be harnessed for medicinal and therapeutic purposes. Among these products, ribosomally synthesized and post-translationally modified peptides, or RiPPs, have garnered increasing attention.

Recently in a new study published in Nature Chemistry, a team of researchers at the University of Illinois Urbana-Champaign uncovered a novel class of hybrid gene clusters, that combines elements of RiPP biosynthesis with enzymes responsible for fatty acid synthesis. They named this newly discovered RiPP hybrid ‘lipoavitide’.

While hybrid gene clusters containing machinery from multiple natural product families are not uncommon in nature, only a few RiPPs have been found to be synthesized by such hybrid machinery. According to Huimin Zhao (BSD theme leader/CABBI/CGD/MMG), Steven L. Miller Chair of Chemical and Biomolecular Engineering at Illinois and anchoring author on the study, hybrid molecules theoretically possess increased versatility and functionality due to their mixed origins from different natural product classes, making them highly sought after.

“We're always interested in looking for novel RiPPs, and by definition, hybrids are novel because they give way to new structures,” said Zhao. “However, even though they occur naturally, they have been rarely studied. There are only three examples in the past that have shown that RiPPs can actually be fused with another class of natural products’ biosynthetic machinery to make hybrid compounds.”

Using advanced bioinformatics tools, the researchers first identified RiPP gene clusters of interest within Streptomyces bacteria. They then looked within these clusters for additional genes associated with other classes of natural products. Ultimately, they identified a cluster that included a gene linked to fatty acid biosynthesis.

The researchers then employed a method called ‘Cas12a assisted precise targeted cloning using in vivo Cre-lox recombination’, or CAPTURE for short, to extract the target DNA fragment containing the gene cluster that encodes the lipoavitide from its native host. The fragment is then cloned and expressed in a more manageable host organism, like Escherichia coli.

Lipoavitides are uniquely amphiphilic, consisting of both a hydrophobic fatty acid and a hydrophilic peptide. This allows them to interact with the membranes of cells, which also have both hydrophobic and hydrophilic components, something that peptide-based RiPPs alone cannot do.

While testing the lipoavitides for bioactivity, Zhao’s team discovered that the fatty acid component of the molecule also allowed for hemolytic activity, the ability to break down the cell walls of blood cells, which could have potential applications in medicine.

Zhao envisions lipoavitides as prototypes for the creation and discovery of other RiPP/fatty acid hybrids. Structural similarities between lipoavitides and other ribosomally synthesized peptides, such as thioamitides (which are used to treat thyroid hyperactivity), indicate further avenues for exploration into their biological functions.

The team hopes that new assays will allow for continued investigation of the bioactivity of these hybrid molecules.
“The challenge in natural product discovery is that we’re limited by the assays we can perform, which can make it hard to find the true application for the natural product,” explained Zhao. “We found that the fatty acid component allows for hemolytic activity, but we don’t know what the exact target of this is. But publishing this work is the first step, and it allows for others to approach us with new tests or assays that might uncover its true bioactivity.”

The discovery and characterization of lipoavitides represent a significant advancement in understanding the biosynthesis of ribosomally derived lipopeptides. Moreover, it opens up promising pathways for leveraging hybrid biosynthetic pathways in drug development, potentially leading to the creation of innovative therapeutics.
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The study was funded by the National Institutes of Health, and can be found at DOI: 10.1038/s41557-024-01491-3

Some animals possess the remarkable ability to regenerate lost structures, exemplified by a lizard regrowing its tail. However, this regenerative process must be tightly regulated by the body to ensure proper tissue organization and to prevent abnormal growths, such as cancer. Yet, the precise mechanisms underlying this regulation are not well known. In a recent study published in PLOS Genetics, researchers at the University of Illinois Urbana-Champaign have identified an RNA-regulator called Brat as a key player in restraining tissue regeneration through its modulation of downstream growth factors.

“There are constraints and protective factors that are important for making sure that regenerating tissue minimizes mistakes, but these haven’t been well studied,” said Rachel Smith-Bolton (GNDP/RBTE), an associate professor and associate head of cell and developmental biology. “When tissue regenerates, such as from a wound, even without any mutations, it sometimes makes mistakes, which I find really interesting. We want to explore what are the mistakes that can happen, and how can you protect against those mistakes.”

The team, led by Smith-Bolton, along with Syeda Nayab Fatima Abidi, a former graduate student in Smith-Bolton’s lab and first author on the study, and Felicity Ting-Yu Hsu, a current graduate student in the lab, investigated the genetic factors influencing regeneration of wing imaginal discs in Drosophila melanogaster, the common fruit fly. Drosophila larvae harbor imaginal discs, which serve as precursors for various appendages like wings, legs, and antennae. The intricate expression of genes within these discs dictates cell fate, or what appendage the cells will become, and the patterning.

Smith-Bolton says the process can be thought of in terms of growing a hand — the cells may be instructed to become fingers, but the patterning is what ensures you don’t end up with 5 thumbs rather than the usual fingers.  

To determine the genes involved in this process, the researchers induced cell death in the wing imaginal discs of fly larvae, resulting in damaged wing discs that subsequently regenerated during development. By comparing wings of adult flies with various mutations to those of control flies, they pinpointed Brat, an mRNA regulator, as a crucial component in regenerative growth. Flies with a mutation that reduced Brat were better able to regenerate their developing wings compared to controls, indicating that Brat specifically works to restrain and control regenerative growth.

“The way fly genes are named is based on the mutant phenotype,” explained Abidi. “Brat gets its full name, Brain Tumor, because in mutants it causes tumors in the brain. This is because it controls whether stem cells are able to differentiate or not. However, there are no stem cells in wing imaginal discs, so it’s interesting that in our results Brat is still essentially performing the same kind of function, controlling whether and how much cells differentiate.”
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While flies with reduced Brat demonstrated improved wing regeneration, this enhancement came with a trade-off: they exhibited a deficiency in bristles and veins within specific wing patches where damage had occurred. According to the researchers, this suggests a misstep in cell-fate specification at the wing margin, attributable to the unrestrained growth facilitated by reduced Brat expression.

Further investigation revealed that Myc, a downstream target of Brat and a growth factor, also plays a pivotal role in this process. Flies with Myc overexpression mirrored the phenotypes observed in Brat-reduced flies, underscoring the delicate balance required for proper regeneration.

“Brat reduces expression of its targets, and because Myc is a target of Brat, overexpressing Myc seems to result in the same phenotype as reducing Brat,” explained Smith-Bolton. “What was really interesting is no matter what we tried, we weren’t able to do the opposite and reduce Myc expression using our normal tools and tricks. This tells us that Myc is probably very tightly regulated in regenerating tissue.”

Hsu's ongoing research focuses on elucidating Myc's role in regeneration and its regulatory mechanisms. In her recent work, she was able to find an existing allele that causes underexpression of Myc in the flies. Surprisingly, this underexpression resulted in similar phenotypes to overexpression of Myc, suggesting a delicate balance in Myc’s expression is needed for proper regeneration.

“This just underscores the fact that you need the right amount of Myc during regeneration or you’re going to get mistakes,” said Smith-Bolton. “And we’re exploring now exactly what that amount is and how it’s regulated.”

Overall, the researchers concluded that Brat appears to act as a protective growth factor, constraining downstream growth factors such as Myc, and preventing errors in cell patterning and cell fate in regenerating tissue.

Given the presence of Brat orthologs — genes with similar function — in various species, including humans, these findings open the door for understanding and potentially manipulating regeneration in human contexts, particularly in curbing uncontrolled growth as seen in cancer.

“Though we didn’t look specifically at cancer, that is definitely the concern when you have a regenerative process that is unchecked, because the potential is that it could develop into a tumor,” said Abidi. “There have to be mechanisms in place that stop the process at the right time so that you are not just getting like a blob of growth, you're getting something that's functional. Uncovering the mutations that lead to unconstrained growth like this is a step towards understanding how those kinds of cancers develop.”
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The study was funded by the National Institutes of Health and the Roy J. Carver Charitable Trust, can be found at https://doi.org/10.1371/journal.pgen.1011103