Bubbling, frothing and sloshing: Long-hypothesized plasma instabilities finally observed

Whether between galaxies or within doughnut-shaped fusion devices known as tokamaks, the electrically charged fourth state of matter known as plasma regularly encounters powerful magnetic fields, changing shape and sloshing in space. Now, a new measurement technique using protons, subatomic particles that form the nuclei of atoms, has captured details of this sloshing for the first time, potentially providing insight into the formation of enormous plasma jets that stretch between the stars.

Scientists at the U.S. Department of Energy's (DOE) Princeton Plasma Physics Laboratory (PPPL) created detailed pictures of a magnetic field bending outward because of the pressure created by expanding plasma. As the plasma pushed on the magnetic field, bubbling and frothing known as magneto-Rayleigh Taylor instabilities arose at the boundaries, creating structures resembling columns and mushrooms.

Then, as the plasma's energy diminished, the magnetic field lines snapped back into their original positions. As a result, the plasma was compressed into a straight structure resembling the jets of plasma that can stream from ultra-dense dead stars known as black holes and extend for distances many times the size of a galaxy. The results suggest that those jets, whose causes remain a mystery, could be formed by the same compressing magnetic fields observed in this research.

"When we did the experiment and analyzed the data, we discovered we had something big," said Sophia Malko, a PPPL staff research physicist and lead scientist on the paper. "Observing magneto-Rayleigh Taylor instabilities arising from the interaction of plasma and magnetic fields had long been thought to occur but had never been directly observed until now. This observation helps confirm that this instability occurs when expanding plasma meets magnetic fields. We didn't know that our diagnostics would have that kind of precision. Our whole team is thrilled!"

"These experiments show that magnetic fields are very important for the formation of plasma jets," said Will Fox, a PPPL research physicist and principal investigator of the research reported in Physical Review Research. "Now that we might have insight into what generates these jets, we could, in theory, study giant astrophysical jets and learn something about black holes."

PPPL has world-renowned expertise in developing and building diagnostics, sensors that measure properties like density and temperature in plasma in a range of conditions. This achievement is one of several in recent years that illustrates how the Lab is advancing measurement innovation in plasma physics.

Using a new technique to produce unprecedented detail

The team improved a measurement technique known as proton radiography by creating a new variation for this experiment that would allow for extremely precise measurements. To create the plasma, the team shone a powerful laser at a small disk of plastic. To produce protons, they shone 20 lasers at a capsule containing fuel made of varieties of hydrogen and helium atoms. As the fuel heated up, fusion reactions occurred and produced a burst of both protons and intense light known as X-rays.

The team also installed a sheet of mesh with tiny holes near the capsule. As the protons flowed through the mesh, the outpouring was separated into small, separate beams that were bent because of the surrounding magnetic fields. By comparing the distorted mesh image to an undistorted image produced by X-rays, the team could understand how the magnetic fields were pushed around by the expanding plasma, leading to whirl-like instabilities at the edges.

"Our experiment was unique because we could directly see the magnetic field changing over time," Fox said. "We could directly observe how the field gets pushed out and responds to the plasma in a type of tug of war."

Diversifying a research portfolio

The findings exemplify how PPPL is expanding its focus to include research focused on high energy density (HED) plasma. Such plasmas, like the one created in this experiment's fuel capsule, are hotter and denser than those used in fusion experiments. "HED plasma is an exciting area of growth for plasma physics," Fox said. "This work is part of PPPL's efforts to advance this field. The results show how the Laboratory can create advanced diagnostics to give us new insights into this type of plasma, which can be used in laser fusion devices, as well as in techniques that use HED plasma to create radiation for microelectronics manufacturing."

"PPPL has an enormous amount of knowledge and experience in magnetized plasmas that can contribute to the field of laser-produced HED plasmas and help make significant contributions," Fox said.

"HED science is complex, fascinating and key to understanding a wide range of phenomena," said Laura Berzak Hopkins, PPPL's associate laboratory director for strategy and partnerships and deputy chief research officer. "It's incredibly challenging to both generate these conditions in a controlled manner and develop advanced diagnostics for precision measurements. These exciting results demonstrate the impact of integrating PPPL's breadth of technical expertise with innovative approaches."

More experiments and better simulations

The researchers plan to work on future experiments that will help improve models of expanding plasma. "Scientists have assumed that in these situations, density and magnetism vary directly, but it turns out that that's not true," Malko said.

"Now that we have measured these instabilities very accurately, we have the information we need to improve our models and potentially simulate and understand astrophysical jets to a higher degree than before," Malko said. "It's interesting that humans can make something in a laboratory that usually exists in space."

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Agricultural impact of flooding

I can barely hear Esther Ngumbi over the roar of greenhouse fans as she shows me around her rooftop laboratory in Morrill Hall. The benches are full of tomato plants, and the tomatoes don't look good. Half of the plants are submerged in bins of water. Their leaves are yellow and withering. Some of the dying tomatoes have flowered. I see one or two baby tomatoes on a couple of spindly plants.

This isn't the only torture inflicted on the tomatoes. Someone has tied little baggies to their stems. Inside the bags, fat green caterpillars are chowing down on the tomato leaves.

Entomology professor Ngumbi has questions -- lots of them -- and this is how she's set out to answer some of them. She is purposely flooding the tomatoes to see how they might respond to flooded conditions in farmers' fields -- a scenario that is becoming more common as a result of climate change.

"In nature, there are many stressors on plants during flooding," Ngumbi says. "Once the tomatoes get flooded, they're already weak, so most likely they will be attracting insects, which like to eat weaker plants. We're investigating how the plants deal with the combined stress of flooding and herbivory."

This explains the caterpillars. They are the larval form of Manduca sexta, the tobacco hornworm. They are feasting on one of the two heirloom tomato varieties Ngumbi is using in the experiment: Cherokee purple and striped German.

Half of the tomato plants in the greenhouse are not flooded, allowing the team to compare the stressed plants with those grown in more common conditions. But there are more investigations going on here.

"Also, within this experiment, we're looking at the microbes," Ngumbi says. "We want to understand how the microbial community changes in flooded conditions."

One of Ngumbi's key focuses is how soil microbes influence plant health and productivity. She's fascinated by mycorrhizal fungi, which form intimate associations with plant roots, offering essential elements like nitrogen to the plants in exchange for glucose supplied by the roots.

The tomato plants are all growing in soil from an Illinois farm, but half were also inoculated with mulch from a local farmer who has developed his own recipe for nurturing mycorrhizal fungi in the soil. Ngumbi wants to see if this inoculation makes any difference to the plants' ability to defend themselves from the fat caterpillars.

To measure plant defenses, Ngumbi's team collects samples of gases emitted by the plants and screens them for volatile organic compounds, the chemicals plants use to ward off bugs that would eat them.

Two years later, Ngumbi publishes the results of these and other laboratory experiments. She found that the two tomato varieties differed in gene expression and in the volatile compounds they emitted -- before any intervention. And when flooded, both varieties of tomatoes had very different chemical emission profiles than when grown in normal conditions. Herbivory influenced the production of these volatile compounds, but not as much as flooding did.

Today, the experiments continue, and Ngumbi's interest in the effects of flooding has only intensified. In a new review published in the journal Trends in Plant Research, she spells out the many changes that occur when plants are inundated with water for days or weeks at a time.

"Flooding is different from other climate-related stressors because it deprives plants of oxygen, an essential and indispensable element and substrate for plant growth and development," Ngumbi writes. Flooding disrupts plant metabolism and energy generation. It interferes with photosynthesis. Flooding kills beneficial bacteria and promotes pathogenic microbes in the soil. It also can compromise plants' ability to defend themselves from disease and harmful insects like the tobacco hornworm.

Ngumbi also warns that increased flooding can undermine decades of research aimed at making plants more resilient to climate change. Flooding may thwart efforts to build soil quality and microbial health to make crops more resilient to stressors such as heat and drought. Flooding also may eliminate gains derived from genetic engineering or plant breeding.

With flooding intensity and frequency predicted to increase by roughly 7% for every 1° C increase in global average temperatures, Ngumbi writes, scientists must consider the impacts of floods to "protect the monumental gains made in building climate-resilient crops."

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Drug may stop migraines before headache starts

When taken at the first signs of a migraine, before headache pain begins, a drug called ubrogepant may be effective in helping people with migraine go about their daily lives with little or no symptoms, according to a new study published in the August 28, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study focused on people with migraine who could tell when an attack was about to happen, due to early symptoms such as sensitivity to light and sound, fatigue, neck pain or stiffness, or dizziness.

Ubrogepant is a calcitonin gene-related peptide receptor antagonist, or CGRP inhibitor. CGRP is a protein that plays a key role in the migraine process.

"Migraine is one of the most prevalent diseases worldwide, yet so many people who suffer from this condition do not receive treatment or report that they are not satisfied with their treatment," said study author Richard B. Lipton, MD, of Albert Einstein College of Medicine in Bronx, New York, and Fellow of the American Academy of Neurology. "Improving care at the first signs of migraine, even before headache pain begins, can be a key to improved outcomes. Our findings are encouraging, suggesting that ubrogepant may help people with migraine function normally and go about their day."

The study involved 518 participants who had migraine for at least one year and two to eight migraine attacks per month in the three months before the study. All of the participants regularly experienced signs that a migraine would be starting within the next few hours. Participants were asked to treat two attacks during a two-month period.

Researchers divided participants into two groups. The first group received a placebo for their first set of pre-headache symptoms of migraine, followed by taking 100 milligrams (mg) of ubrogepant for their second instance of symptoms. The second group took ubrogepant for the first instance and placebo for the second instance.

Participants evaluated limitations on their activity in their diary using a scale ranging from zero to five, with 0 meaning "not at all limited -- I could do everything"; 1, "a little limited"; 2, "somewhat limited"; 3, "very limited"; or 4, "extremely limited."

Twenty-four hours after taking the drug or a placebo, 65% of people who took ubrogepant reported themselves as "not at all limited -- I could do everything," or "a little limited," compared to 48% of those who took the placebo.

Researchers found that as early as two hours post-medication, people who took the drug were 73% more likely to report that they had "no disability, able to function normally," than those who took the placebo.

"Based on our findings, treatment with ubrogepant may allow people with migraine who experience early warning signs before a migraine occurs to quickly treat migraine attacks in their earliest stages and go about their daily lives with little discomfort and disruption," said Lipton. "This could lead to an improved quality of life for those living with migraine."

Lipton noted that participants showed that based on their headache warning symptoms, they could reliably predict impending migraine headaches. These findings apply only to those with reliable warning symptoms.

A limitation of the study was that participants recorded their symptoms and medication use in electronic diaries, so it is possible some people may not have recorded all information accurately.

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Dancing galaxies make a monster at the cosmic dawn

Astronomers have spotted a pair of galaxies in the act of merging 12.8 billion years ago. The characteristics of these galaxies indicate that the merger will form a monster galaxy, one of the brightest types of objects in the Universe. These results are important for understanding the early evolution of galaxies and black holes in the early Universe.

Quasars are bright objects powered by matter falling into a supermassive black hole at the center of a galaxy in the early Universe.

The most accepted theory is that when two gas-rich galaxies merge to form a single larger galaxy, the gravitational interaction of the two galaxies causes gas to fall towards the supermassive black hole in one or both of the galaxies, causing quasar activity.

To test this theory, an international team of researchers led by Takuma Izumi used the ALMA (Atacama Large Millimeter/submillimeter Array) radio telescope to study the earliest known pair of close quasars.

This pair was discovered by Yoshiki Matsuoka, at Ehime University in Japan, in images taken by the Subaru Telescope.

Located in the direction of the constellation Virgo, this pair of quasars existed during the first 900 million years of the Universe.

The pair is dim, indicating that the quasars are still in the early stages of their evolution.

The ALMA observations mapped the host galaxies of the quasars and showed that the galaxies are linked by a "bridge" of gas and dust.

This indicates that the two galaxies are in fact merging.

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How a salt giant radically reshaped Mediterranean marine biodiversity

A new study paves the way to understanding biotic recovery after an ecological crisis in the Mediterranean Sea about 5.5 million years ago. An international team led by Konstantina Agiadi from the University of Vienna has now been able to quantify how marine biota was impacted by the salinization of the Mediterranean: Only 11 percent of the endemic species survived the crisis, and the biodiversity did not recover for at least another 1.7 million years. The study was just published in the journal Science.

Lithospheric movements throughout Earth history have repeatedly led to the isolation of regional seas from the world ocean and to the massive accumulations of salt. Salt giants of thousands of cubic kilometers have been found by geologists in Europe, Australia, Siberia, the Middle East, and elsewhere. These salt accumulations present valuable natural resources and have been exploited from antiquity until today in mines around the world (e.g. at the Hallstatt mine in Austria or the Khewra Salt Mine in Pakistan).

The Mediterranean salt giant is a kilometer-thick layer of salt beneath the Mediterranean Sea, which was first discovered in the early 1970s. It formed about 5.5 million years ago because of the disconnection from the Atlantic during the Messinian Salinity Crisis. In a study published in the journal Science, an international team of researchers -- comprising 29 scientists from 25 institutes across Europe -- led by Konstantina Agiadi from University of Vienna now was able to quantify the loss of biodiversity in the Mediterranean Sea due to the Messinian crisis and the biotic recovery afterwards.

Huge impact on marine biodiversity

After several decades of painstaking research on fossils dated from 12 to 3.6 million years found on land in the peri-Mediterranean countries and in deep-sea sediment cores, the team found that almost 67% of the marine species in the Mediterranean Sea after the crisis were different than those before the crisis. Only 86 of 779 endemic species (living exclusively in the Mediterranean before the crisis) survived the enormous change in living conditions after the separation from the Atlantic. The change in the configuration of the gateways, which led to the formation of the salt giant itself, resulted in abrupt salinity and temperature fluctuations, but also changed the migration pathways of marine organisms, the flow of larvae and plankton and disrupted central processes of the ecosystem. Due to these changes, a large proportion of the Mediterranean inhabitants of that time, such as tropical reef-building corals, died out.After the reconnection to the Atlantic and the invasion of new species like the Great White shark and oceanic dolphins, Mediterranean marine biodiversity presented a novel pattern, with the number of species decreasing from west to east, as it does today.

Recovery took longer than expected

Because peripheral seas like the Mediterranean are important biodiversity hotspots, it was very likely that the formation of salt giants throughout geologic history had a great impact, but it hadn't been quantified up to now. "Our study now provides the first statistical analysis of such a major ecological crisis," explains Konstantina Agiadi from the Department of Geology. Furthermore, it also quantifies for the first time the timescales of recovery after a marine environmental crisis, which is actually much longer than expected: "The biodiversity in terms of number of species only recovered after more than 1.7 million years," says the geoscientist. The methods used in the study also provide a model connecting plate tectonics, the birth and death of the oceans, Salt, and marine Life that could be applied to other regions of the world.

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This tiny backyard bug does the fastest backflips on earth

Move over, Sonic. There's a new spin-jumping champion in town -- the globular springtail (Dicyrtomina minuta). This diminutive hexapod backflips into the air, spinning to over 60 times its body height in the blink of an eye, and a new study features the first in-depth look at its jumping prowess.

Globular springtails are tiny, usually only a couple millimeters in body length. They don't fly, bite or sting. But they can jump. In fact, jumping is their go-to (and only) plan for avoiding predators. And they excel at it -- to the naked eye it seems as though they vanish entirely when they take off.

"When globular springtails jump, they don't just leap up and down, they flip through the air -- it's the closest you can get to a Sonic the Hedgehog jump in real life," says Adrian Smith, research assistant professor of biology at North Carolina State University and head of the evolutionary biology and behavior research lab at the North Carolina Museum of Natural Sciences. "So naturally I wanted to see how they do it."

Finding the globular springtails was easy enough -- they're all around us. The ones in this study are usually out from December through March. Smith "recruited" his research subjects by sifting through leaf litter from his own backyard. But the next part proved to be the most challenging.

"Globular springtails jump so fast that you can't see it in real time," Smith says. "If you try to film the jump with a regular camera, the springtail will appear in one frame, then vanish. When you look at the picture closely, you can see faint vapor trail curlicues left behind where it flipped through the one frame."

Smith solved that problem by using cameras that shoot 40,000 frames per second. He urged the springtails to jump by shining a light on them or lightly prodding them with an artist's paintbrush. Then he looked at how they took off, how fast and far they went, and how they landed.

Globular springtails don't use their legs to jump. Instead, they have an appendage called a furca that folds up underneath their abdomen and has a tiny, forked structure at its tip. When the springtails jump, the furca flips down and the forked tip pushes against the ground, launching them into a series of insanely fast backflips.

What do we mean by insanely fast?

"It only takes a globular springtail one thousandth of a second to backflip off the ground and they can reach a peak rate of 368 rotations per second," Smith says. "They accelerate their bodies into a jump at about the same rate as a flea, but on top of that they spin. No other animal on earth does a backflip faster than a globular springtail."

The springtails were also able to launch themselves over 60 millimeters into the air -- more than 60 times their own height. And in most cases, they went backward.

"They can lean into a jump and go slightly sideways, but when launching from a flat surface, they mostly travel up and backward, never forward," says Jacob Harrison, a postdoctoral researcher at the Georgia Institute of Technology and paper co-author. "Their inability to jump forward was an indication to us that jumping is primarily a means to escape danger, rather than a form of general locomotion."

Landing was found in two styles: uncontrolled and anchored. Globular springtails do have a sticky forked tube they can evert -- or push out of their bodies -- to grapple a surface or halt their momentum, but Smith observed that bouncing and tumbling to a stop was just as common as anchored landings.

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Highest-resolution observations yet from the surface of Earth

The Event Horizon Telescope (EHT) Collaboration has conducted test observations, using the Atacama Large Millimeter/submillimeter Array (ALMA) and other facilities, that achieved the highest resolution ever obtained from the surface of Earth. They managed this feat by detecting light from distant galaxies at a frequency of around 345 GHz, equivalent to a wavelength of 0.87 mm. The Collaboration estimates that in future they will be able to make black hole images that are 50% more detailed than was possible before, bringing the region immediately outside the boundary of nearby supermassive black holes into sharper focus. They will also be able to image more black holes than they have done so far. The new detections, part of a pilot experiment, were published today in The Astronomical Journal.

The EHT Collaboration released images of M87*, the supermassive black hole at the centre of the M87 galaxy, in 2019, and of Sgr A*, the black hole at the heart of our Milky Way galaxy, in 2022. These images were obtained by linking together multiple radio observatories across the planet, using a technique called very long baseline interferometry (VLBI), to form a single 'Earth-sized' virtual telescope.

To get higher-resolution images, astronomers typically rely on bigger telescopes -- or a larger separation between observatories working as part of an interferometer. But since the EHT was already the size of Earth, increasing the resolution of their ground-based observations called for a different approach. Another way to increase the resolution of a telescope is to observe light of a shorter wavelength -- and that's what the EHT Collaboration has now done.

"With the EHT, we saw the first images of black holes using the 1.3-mm wavelength observations, but the bright ring we saw, formed by light bending in the black hole's gravity, still looked blurry because we were at the absolute limits of how sharp we could make the images," said the study's co-lead Alexander Raymond, previously a postdoctoral scholar at the Center for Astrophysics | Harvard & Smithsonian (CfA), and now at the Jet Propulsion Laboratory, both in the United States. "At 0.87 mm, our images will be sharper and more detailed, which in turn will likely reveal new properties, both those that were previously predicted and maybe some that weren't."

To show that they could make detections at 0.87 mm, the Collaboration conducted test observations of distant, bright galaxies at this wavelength. Rather than using the full EHT array, they employed two smaller subarrays, both of which included ALMA and the Atacama Pathfinder EXperiment (APEX) in the Atacama Desert in Chile. The European Southern Observatory (ESO) is a partner in ALMA and co-hosts and co-operates APEX. Other facilities used include the IRAM 30-meter telescope in Spain and the NOrthern Extended Millimeter Array (NOEMA) in France, as well as the Greenland Telescope and the Submillimeter Array in Hawai'i.

In this pilot experiment, the Collaboration achieved observations with detail as fine as 19 microarcseconds, meaning they observed at the highest-ever resolution from the surface of Earth. They have not been able to obtain images yet, though: while they made robust detections of light from several distant galaxies, not enough antennas were used to be able to accurately reconstruct an image from the data.

This technical test has opened up a new window to study black holes. With the full array, the EHT could see details as small as 13 microarcseconds, equivalent to seeing a bottle cap on the Moon from Earth. This means that, at 0.87 mm, they will be able to get images with a resolution about 50% higher than that of previously released M87* and SgrA* 1.3-mm images. In addition, there's potential to observe more distant, smaller and fainter black holes than the two the Collaboration has imaged thus far.

EHT Founding Director Sheperd "Shep" Doeleman, an astrophysicist at the CfA and study co-lead, says: "Looking at changes in the surrounding gas at different wavelengths will help us solve the mystery of how black holes attract and accrete matter, and how they can launch powerful jets that stream over galactic distances."

This is the first time that the VLBI technique has been successfully used at the 0.87 mm wavelength. While the ability to observe the night sky at 0.87 mm existed before the new detections, using the VLBI technique at this wavelength has always presented challenges that took time and technological advances to overcome. For example, water vapour in the atmosphere absorbs waves at 0.87 mm much more than it does at 1.3 mm, making it more difficult for radio telescopes to receive signals from black holes at the shorter wavelength. Combined with increasingly pronounced atmospheric turbulence and noise buildup at shorter wavelengths, and an inability to control global weather conditions during atmospherically sensitive observations, progress to shorter wavelengths for VLBI -- especially those that cross the barrier into the submillimetre regime -- has been slow. But with these new detections, that's all changed.

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Number of fish species at risk of extinction fivefold higher than previous estimates, according to a new prediction

Researchers predict that 12.7% of marine teleost fish species are at risk of extinction, up fivefold from the International Union for Conservation of Nature's prior estimate of 2.5%. Nicolas Loiseau and Nicolas Mouquet from the MARBEC Unit (the Marine Biodiversity, Exploitation and Conservation Unit) in Montpellier, France, and colleagues report these findings in a study published August 29th in the open-access journal PLOS Biology. Their report includes nearly 5,000 species that did not receive an IUCN conservation status due to insufficient data.

The IUCN's Red List of Threatened Species tracks more than 150,000 species to guide global conservation efforts on behalf of the most threatened.

However, 38% of marine fish species (or 4,992 species at the time of this research) are considered Data-Deficient and do not receive an official conservation status or the associated protections.

To better direct conservation efforts toward the species that need them, Loiseau and colleagues combined a machine learning model with an artificial neural network to predict the extinction risks of Data-Deficient species.

The models were trained on occurrence data, biological traits, taxonomy and human uses from 13,195 species.

They categorized 78.5% of the 4,992 species as Non-Threatened or Threatened (which includes Critically Endangered, Endangered and Vulnerable IUCN categories). Predicted Threatened species increased fivefold (from 334 to 1,671) and predicted Non-Threatened species increased by a third (from 7,869 to 10,451).

Predicted Threatened species tended to have a small geographic range, large body size and low growth rate.

The extinction risk was also correlated with shallow habitats.

The South China Sea, the Philippine and Celebes Seas and the west coasts of Australia and North America emerged as hotspots for predicted Threatened species.

The researchers recommend increased research and conservation efforts in these areas.

The researchers observed "a marked change in conservation priority ranking after species IUCN predictions," recommending that the Pacific Islands and Southern Hemisphere's polar and subpolar regions be prioritized to account for emerging at-risk species.

Many species that remained Data-Deficient occur in the Coral Triangle, indicating that additional research is needed there.

The researchers note that models cannot replace direct evaluations of at-risk species but AI offers a unique opportunity to provide a rapid, extensive and cost-effective evaluation of extinction risk of species.

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Researchers map 50,000 of DNA's mysterious 'knots' in the human genome

Innovative study of DNA's hidden structures may open up new approaches for treatment and diagnosis of diseases, including cancer.

DNA is well-known for its double helix shape. But the human genome also contains more than 50,000 unusual 'knot'-like DNA structures called i-motifs, researchers at the Garvan Institute of Medical Research have discovered.

Published today in The EMBO Journalis the first comprehensive map of these unique DNA structures, shedding light on their potential roles in gene regulation involved in disease.

In a landmark 2018 study, Garvan scientists were the first to directly visualise i-motifs inside living human cells using a new antibody tool they developed to recognise and attach to i-motifs. The current research builds on those findings by deploying this antibody to identify i-motif locations across the entire genome.

"In this study, we mapped more than 50,000 i-motif sites in the human genome that occur in all three of the cell types we examined," says senior author Professor Daniel Christ, Head of the Antibody Therapeutics Lab and Director of the Centre for Targeted Therapy at Garvan. "That's a remarkably high number for a DNA structure whose existence in cells was once considered controversial. Our findings confirm that i-motifs are not just laboratory curiosities but widespread -- and likely to play key roles in genomic function."

Curious DNA i-motifs could play a dynamic role in gene activity

I-motifs are DNA structures that differ from the iconic double helix shape. They form when stretches of cytosine letters on the same DNA strand pair with each other, creating a four-stranded, twisted structure protruding from the double helix.

The researchers found that i-motifs are not randomly scattered but concentrated in key functional areas of the genome, including regions that control gene activity.

"We discovered that i-motifs are associated with genes that are highly active during specific times in the cell cycle. This suggests they play a dynamic role in regulating gene activity," says Cristian David Peña Martinez, a research officer in the Antibody Therapeutics Lab and first author of the study.

"We also found that i-motifs form in the promoter region of oncogenes, for instance the MYC oncogene, which encodes one of cancer's most notorious 'undruggable' targets. This presents an exciting opportunity to target disease-linked genes through the i-motif structure," he says.

I-motifs hold promise for new type of therapies and diagnostics

"The widespread presence of i-motifs near these 'holy grail' sequences involved in hard-to-treat cancers opens up new possibilities for new diagnostic and therapeutic approaches. It might be possible to design drugs that target i-motifs to influence gene expression, which could expand current treatment options," says Associate Professor Sarah Kummerfeld, Chief Scientific Officer at Garvan and co-author of the study.

Professor Christ adds that mapping i-motifs was only possible thanks to Garvan's world-leading expertise in antibody development and genomics. "This study is an example of how fundamental research and technological innovation can come together to make paradigm-shifting discoveries," he says.

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Gene therapy gets a turbo boost

For decades, scientists have dreamt of a future where genetic diseases, such as the blood clotting disorder hemophilia, could be a thing of the past. Gene therapy, the idea of fixing faulty genes with healthy ones, has held immense promise. But a major hurdle has been finding a safe and efficient way to deliver those genes.

Now, researchers at the University of Hawai'i's John A. Burns School of Medicine (JABSOM) have made a significant breakthrough in gene editing technology that could revolutionize how we treat genetic diseases. Their new method offers a faster, safer, and more efficient way to deliver healthy genes into the body, potentially leading to treatments for hundreds of conditions. This research was recently published in Nucleic Acids Research.

Here's how it works.

Current methods can fix errors in genes, but they can also cause unintended damage by creating breaks in the DNA. Additionally, they struggle to insert large chunks of genetic material such as whole genes.

The new technique, developed by Dr. Jesse Owens along with his team Dr. Brian Hew, Dr. Ryuei Sato and Sabranth Gupta, from JABSOM's Institute for Biogenesis Research and Cell and Molecular Biology Department, addresses these limitations. They used laboratory evolution to generate a new super-active integrase capable of inserting therapeutic genes into the genome at record-breaking efficiencies.

"It's like having a "paste" function for the human genome," said Dr. Owens. "It uses specially engineered 'integrases' to carefully insert healthy genes into the exact location needed, without causing breaks in the DNA. This method is much more efficient, with success rates of up to 96% in some cases."

"This could lead to faster and more affordable treatments for a wide range of diseases, potentially impacting hundreds of conditions with a single faulty gene," said Dr. Owens.

Faster Development of Treatments and a Broader Range of Applications

The implications of this research extend beyond gene therapy. The ability to efficiently insert large pieces of DNA has applications in other areas of medicine.

When making cell lines to produce therapeutic proteins, the gene encoding the protein is usually randomly inserted into the genome, and it rarely lands in a location in the genome that is good for production. This is like searching for a needle in a haystack. Additionally, finding a cell with the gene inserted correctly and producing the desired protein can take many months.

Instead of searching for a needle in a haystack, Dr. Owens' technique makes a stack of needles. It delivers the gene directly to the desired location, significantly speeding up the development process.

"JABSOM takes pride in nurturing talented researchers like Jesse Owens, whose work has the power to create a global impact," said Sam Shomaker, dean of the University of Hawai'i John A. Burns School of Medicine. "This research, conducted in our lab in the middle of the Pacific, has the potential to significantly improve the way we treat genetic diseases."

Dr. Owens' team is exploring how this technique could accelerate the development and manufacture of biologics and advanced therapies such as antibodies. Currently, finding the right cell line for efficient production can be a time-consuming process. However, Dr. Owens' new genome engineering tool can reduce the cell line development timeline and accelerate the manufacture of life-saving therapeutics.

Read more at Science Daily