Chemists funded by the U.S. National Science Foundation have developed a new process to synthesize a plant-based compound that shows effectiveness against triple-negative breast cancer cells. According to the American Cancer Society (link is external) , triple-negative breast cancer is one of the most aggressive types of breast cancer and accounts for 10-15% of all breast cancer cases. The process also increases the compound's potency against these cancer cells and provides a method for it to be mass-produced to enable further testing as a potential treatment. The new process can also be used broadly to help discover new medicines by synthesizing and testing other complex organic compounds. The findings were achieved by Emory University researchers and published in The Journal of the American Chemical Society (link is external) . The compound — called phaeocaulisin A — is extracted from the flowering plant Curcuma phaeocaulis, a relative of ginger and turmeric used for centuries in traditional medicine. "We not only efficiently replicated a complex natural product, we also improved upon it by turning it into a more potent compound," says Mingji Dai, professor of chemistry and co-lead of the study. "It is only the first step in a long process," says Yong Wan, professor of pharmacology and chemical biology and study co-lead. "But the new analogue of phaeocaulisin A we have reported shows promising efficacy against triple-negative breast cancer cells, which are very aggressive and challenging to deal with." The study describes how the unique molecular structure of phaeocaulisin A works against triple-negative breast cancer by inhibiting it as a particularly effective anti-inflammatory agent. Wan and Dai were drawn to understand this property and improve upon it with their lab-synthesized analogue version. Mingji Dai (right), professor of chemistry at Emory University, and Yong Wan (left), professor of pharmacology and chemical biology at Emory School of Medicine, invented a reaction to streamline the total synthesis of a compound, phaeocaulisin A, extracted from a plant used for centuries in traditional medicine. Credit: Sarah Woods, Emory University Other chemists have synthesized phaeocausilin A before by using a 17-step method. But Wan and Dai wanted to find a more efficient way. In the process, they devised a new type of chemical reaction to create complex molecules: palladium-catalyzed carbonylation, which uses low-cost and widely available carbon monoxide as a resource. This discovery also cuts down their total synthesis of phaeocausilin A from 17 to 10 steps. "The icing on the cake," says Dai, "is that the chemical reaction we invented holds potential for widespread use in organic chemistry to make many other compounds for drug discovery." "What is so exciting to me about this work is that this methodology can be broadly applied to other synthetic targets. These reactions enable chemists to rethink strategies for how to piece together molecules, like building a Lego set with a different, shorter, set of instructions," says John Jewett, program director in the NSF Division of Chemistry, which supported the research. The chemists say the compound and this method will require years of further research to evaluate its full potential. That said, it's already shown possibilities for production at scale, and in preparation for commercial therapeutic use. "My lab's focus is to find ways to integrate basic research into translational research," Wan says. "We are not only trying to understand the mystery of mechanisms behind cancer. We also want to bring strategies to neutralize cancer to the clinical bedside."

Researchers supported by the U.S. National Science Foundation have discovered four tiny exoplanets orbiting Barnard's star, a red dwarf at the center of the nearest single-star system to Earth. Using a specialized instrument mounted on the NSF-supported Gemini North Telescope in Hawaii, the team detected "wobbles" in the motion of Barnard's star by observing subtle shifts in the color of its light, indicating the gravitational pull from nearby exoplanets. The planets' surfaces are too hot to support life as we know it. The researchers made their discovery using the M-dwarf Advanced Radial velocity Observer Of Neighboring eXoplanets (MAROON-X) spectrometer, which is designed to detect exoplanets. Their results were published in The Astrophysical Journal Letters (link is external) and show promise for finding and confirming more small planets around other red dwarf stars, which are numerous in the universe. "The U.S. National Science Foundation is collaborating with the astronomy community on an adventure to look deeper into the universe to detect planets with environments that might resemble Earth's," says Martin Still, NSF program director for the International Gemini Observatory. "The planet discoveries provided by MAROON-X mounted on Gemini North provide a significant step along that journey." Most of the planets previously discovered in the Milky Way galaxy are much larger than Earth, making detecting these relatively tiny planets a fundamental step towards a more complete understanding of planet populations. Each of the four planets are only 20 to 30% the mass of Earth, and their proximity to Barnard's star causes them to orbit around it in just a matter of days. The fourth planet is the smallest exoplanet ever detected using the radial velocity technique, opening new opportunities for discovering such small planets elsewhere.

A new computational tool developed with support from the U.S. National Science Foundation could greatly speed up determining the 3D structure of RNAs, a critical step in developing new RNA-based drugs, identifying drug-binding sites and using RNAs in other biotechnology and biomedicine applications. The tool, NuFold, leverages state-of-the-art machine learning techniques to predict the structure of a wide variety of RNA molecules from their sequences. This new capability will allow researchers to visualize what a given RNA structure could look like based on its sequence and identify its potential use in drug delivery, disease treatment and other applications. The research leading to NuFold was published in Nature Communications (link is external) . RNAs are critical biological molecules — encoding information, like DNA, and performing cellular functions, like proteins — but relatively few RNA structures have been determined through experimentation thus far, which severely limits understanding of their functions. For example, RNAs in the NSF-funded Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) represent only about 3% of total entries. Experimentally determining RNA structures is often time-consuming and costly. By providing a path to reliably predicting RNA structure from sequence, NuFold could greatly expedite the discovery of RNA function and enable quicker development of RNA-based therapeutics and technologies. Case studies of the predictions of NuFold, an NSF-funded AI-based tool for predicting RNA structures. Credit: Daisuke Kihara, Purdue University. Figure taken from the Nufold paper under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License These therapeutics and technologies could help address a range of diseases and conditions. For example, information on the structure of small interfering RNAs could aid in limiting gene overexpression that can play a role in cancer, neurological disorders and kidney stones. Knowing the structure of RNAs also could help enhance food security by protecting plants from viruses. NuFold leverages state-of-the-art machine learning techniques to predict the structure of a range of RNA molecules from their sequences. The system architecture for NuFold is based on the artificial intelligence-based protein structure prediction tool AlphaFold2, which was trained on the RCSB PDB and whose developers were awarded the 2024 Nobel Prize in chemistry. The source code for NuFold is openly available for use by the broad computational biology research community and other researchers interested in RNA structures. The machine-learning-enabled 3D RNA structures can be realized through novel 3D nanomanufacturing approaches. Learn more about NSF support for biotechnology.

Although a leopard cannot change its spots, new research (link is external) funded by the U.S. National Science Foundation uses the principles that govern patterns like leopard spots to understand biological processes at the nanoscale. The research, which combines physics, biology and theories first suggested by famed code breaker Alan Turing, increases knowledge of protein nanocluster formation and could enhance understanding of the causes of Emery-Dreifuss muscular dystrophy (EDMD) and lead to possible treatments. The project probes the formation of nanoclusters made of a protein called emerin, which plays a role in the structure and function of the membrane around a cell's nucleus. These clusters are extremely important in mechanotransduction, the process by which cells respond to mechanical forces like stretching or pressure. When mechanotransduction fails, it can lead to diseases like EDMD and other forms of muscular dystrophy. Understanding how emerin molecules form nanoclusters will aid in deciphering how the process can be disrupted and how disruptions can lead to disease. While the way in which proteins come together has been studied for some time, the new research uses biophysical concepts to understand the biological processes. Specifically, the researchers used rules that control the formation of patterns proposed by Turing. Turing's work provided mathematical rules that govern the formation of nanoclusters, working at a vastly different scale than leopard spots or zebra stripes. The research was led by Fabien Pinaud, associate professor of biological sciences and physics and astronomy at the University of Southern California Dornsife College of Letters, Arts and Sciences, and Christoph Haselwandter, professor of physics and astronomy and quantitative and computational biology at USC Dornsife.

U.S. National Science Foundation-supported research shows that fires in populated areas are three times more likely to lead to premature deaths than wildfires overall, informing fire mitigation efforts. Scientists at the NSF National Center for Atmospheric Research (NSF NCAR) led the study, published in Science Advances (link is external) , which found that smoke from fires that blaze through the wildland-urban interface (WUI) has far greater health impacts than smoke from wildfires in remote areas. "This research will support the development of advanced fire prevention strategies, improve building codes and lead to effective emergency response plans,” said Bernard Grant, a program director in the NSF Directorate for Geosciences. “It will help protect lives and homes, safeguard natural ecosystems and reduce the economic burden of wildfire disasters,” The researchers used an advanced NSF NCAR-based computer model, the Multi-Scale Infrastructure for Chemistry and Aerosols, to simulate pollutants from fires. Their modeling included carbon monoxide chemical tracers, which allowed them to estimate emission sources and differentiate between wildland and WUI fires. "The health impacts are proportionately large because they're close to human populations," said NSF NCAR scientist Wenfu Tang, the report's lead author. "Pollutants emitted by WUI fires, such as particulate matter and the precursors to ozone, are more harmful because they’re not dispersing across hundreds or thousands of miles."

Funded by multiple grants from the U.S. National Science Foundation, researchers created a functional sponge that can soak up certain pollutants from water and then release them on demand, presenting a reusable and low-cost solution for cleaning storm runoff while simultaneously recovering valuable metals like zinc and copper, as well as phosphate. Using surface iron oxide nanoparticles specialized for capturing specific contaminants, the sponge collects the minerals and then discharges them only when triggered by changes in pH, and it can be used multiple times. The findings were achieved by researchers at Northwestern University and published in the American Chemical Society's journal Environmental Science and Technology Water (link is external) . "The technology can be used as a universal sorbent or 'catch-all,' or it can be tailored to certain groups of contaminants like metals, plastics or nutrients," says Vinayak Dravid, a research author and Northwestern professor of materials science and engineering. In previous iterations, the sponge material has successfully pulled lead, microplastics and oil from water. Industrial manufacturing and agriculture, in particular, experience mineral and fertilizer loss due to runoff, leaving valuable nonrenewable resources as pollutants in bodies of water. Those resources include heavy metals like zinc and copper and also phosphate. Illustration showing how the sponge nanocomposite material recovers phosphate and metals from water. Credit: Kelly Matuszewski, Northwestern University Kelly Matuszewski, doctoral student and first author on the paper, found that lowering water pH flushed out the captured copper and zinc from the sponge. Inversely, raising water pH loosened the phosphates. After five uses of recycling these nutrients, the sponge still worked functionally while yielding water with untraceable levels of those pollutants. "We can't just keep flushing these minerals down the toilet," says Matuszewski. "We need to understand how they interact and find ways to actually utilize them." Co-author Dravid has co-founded a startup to commercialize the sponge-based technology with additional NSF support through the Small Business Innovation Research program, which will further develop the material for real-life scenarios. The team has yet to account for biofilms, clogging or water flow dynamics on the sponge's performance. They plan to explore those in future research while testing the maximum mineral levels the sponge can absorb.

A new study (link is external) by U.S. National Science Foundation-funded researchers on how members of the animal world sense and react to sounds provides insight into adaptations in communication that could be used in the development of adaptable hearing aids or limiting the impact of agricultural pests. "By increasing our understanding of how animals perceive and respond to sounds — especially when those sounds are changing — this research could aid in developing hearing aids that automatically tune as a person walks from a movie theater to a crowded restaurant or other adaptive hearing and acoustics devices," said Jodie Jawor, a program director in the NSF Directorate for Biological Sciences. "It also highlights how agricultural pests can move into an area and capitalize on a new host, harming society in the process — think about a parasite of honeybees that hurts their populations and our food supply." The study focused on the interactions between a species of fly (Ormia ochracea) and Pacific crickets, which are engaged in a sort of sound arms race. The fly can hear the mating chirps of the male cricket and uses the sounds to locate the male, in which the fly lays its eggs. The fly larvae feed on and develop inside of their cricket hosts, eventually killing them when they emerge. Some crickets in Hawaii have responded to this threat by changing the sounds they use to find mates — purring or rattling rather than chirping — but the flies still find them, and the researchers sought to understand how. The research team, led by Norman Lee, an associate professor of biology at St. Olaf College, and Robin Tinghitella, an associate professor of biology at the University of Denver, used a series of lab experiments to test if this was a unique counteradaptation by flies in areas where both they and crickets have been introduced or if the flies had always been able to hear the alternative noises but not focused on them, as in their natural habitats such sounds would not have signaled a cricket. The researchers found that populations of flies from natural and non-natural habitats could hear the purrs, but the flies from areas where they have been introduced were more active in their response to the sounds. This represents a novel change caused by adaptation to a new environment, knowledge that could support advances in assistive hearing devices for humans and shows the growing number of interactions that drive how species communicate.