New findings that map the universe’s cosmic growth support Einstein’s theory of gravity

For millennia, humans have been fascinated by the mysteries of the cosmos.

Unlike ancient philosophers imagining the universe’s origins, modern cosmologists use quantitative tools to gain insights into the universe’s evolution and structure. Modern cosmology dates back to the early 20th century, with the development of Albert Einstein’s theory of general relativity.

Now, researchers from the Atacama Cosmology Telescope (ACT) collaboration have created a groundbreaking new image that reveals the most detailed map of dark matter distributed across a quarter of the entire sky, extending deep into the cosmos. What’s more, it confirms Einstein’s theory of how massive structures grow and bend light, over the entire 14-billion-year life span of the universe.

“We have mapped the invisible dark matter across the sky to the largest distances, and clearly see features of this invisible world that are hundreds of millions of light-years across, says Blake Sherwin, professor of cosmology at the University of Cambridge, where he leads a group of ACT researchers. “It looks just as our theories predict.”

Despite making up 85% of the universe and influencing its evolution, dark matter has been hard to detect because it doesn’t interact with light or other forms of electromagnetic radiation. As far as we know dark matter only interacts with gravity.

To track it down, the more than 160 collaborators who have built and gathered data from the National Science Foundation’s Atacama Cosmology Telescope in the high Chilean Andes observe light emanating following the dawn of the universe’s formation, the Big Bang — when the universe was only 380,000 years old. Cosmologists often refer to this diffuse light that fills our entire universe as the “baby picture of the universe,” but formally, it is known as the cosmic microwave background radiation (CMB).

The team tracks how the gravitational pull of large, heavy structures including dark matter warps the CMB on its 14-billion-year journey to us, like how a magnifying glass bends light as it passes through its lens.

“We’ve made a new mass map using distortions of light left over from the Big Bang,” says Mathew Madhavacheril, assistant professor in the Department of Physics and Astronomy at the University of Pennsylvania. “Remarkably, it provides measurements that show that both the ‘lumpiness’ of the universe, and the rate at which it is growing after 14 billion years of evolution, are just what you’d expect from our standard model of cosmology based on Einstein’s theory of gravity.”

Sherwin adds, “our results also provide new insights into an ongoing debate some have called ‘The Crisis in Cosmology,'”explaining that this crisis stems from recent measurements that use a different background light, one emitted from stars in galaxies rather than the CMB. These have produced results that suggest the dark matter was not lumpy enough under the standard model of cosmology and led to concerns that the model may be broken. However, the team’s latest results from ACT were able to precisely assess that the vast lumps seen in this image are the exact right size.

“When I first saw them, our measurements were in such good agreement with the underlying theory that it took me a moment to process the results,” says Cambridge Ph.D. student Frank Qu, part of the research team. “It will be interesting to see how this possible discrepancy between different measurements will be resolved.”

“The CMB lensing data rivals more conventional surveys of the visible light from galaxies in their ability to trace the sum of what is out there,” says Suzanne Staggs, director of ACT and Henry DeWolf Smyth Professor of Physics at Princeton University. “Together, the CMB lensing and the best optical surveys are clarifying the evolution of all the mass in the universe.”

“When we proposed this experiment in 2003, we had no idea the full extent of information that could be extracted from our telescope,” says Mark Devlin, the Reese Flower Professor of Astronomy at the University of Pennsylvania and the deputy director of ACT. “We owe this to the cleverness of the theorists, the many people who built new instruments to make our telescope more sensitive, and the new analysis techniques our team came up with.”

ACT, which operated for 15 years, was decommissioned in September 2022. Nevertheless, more papers presenting results from the final set of observations are expected to be submitted soon, and the Simons Observatory will conduct future observations at the same site, with a new telescope slated to begin operations in 2024. This new instrument will be capable of mapping the sky almost 10 times faster than ACT.

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Better understanding the physics of our universe

For the last six years, Indiana University researchers and collaborators from around the world have sought to answer important questions about the most basic laws of physics that govern our universe. Their experiment, the Majorana Demonstrator, has helped to push the horizons on research concerning one of the fundamental building blocks of the universe: neutrinos.

The experiment’s final report was published in Physical Review Letters in February.

Neutrinos — subatomic particles similar to an electron but that have no electric charge — are the second most abundant particles in the universe after light. However, they are some of the hardest particles to measure because they do not interact the way other particles do.

“Neutrinos have a profound impact on the universe and physics at every imaginable scale, surprising us down at the particle interaction level and having broad impact up through the cosmic scales,” said Walter Pettus, an assistant professor of physics in the IU College of Arts and Sciences. “But they are also the most frustrating to study because we know so much about them, yet we have so many gaps.”

The Majorana Demonstrator, a collaboration of 60 researchers from 24 institutions, was designed to fill many of those gaps at the same time, probing into the most fundamental properties of neutrinos.

One aspect they hoped to observe was whether the neutrino could be its own antiparticle — a subatomic particle of the same mass but with the opposite electric charge. Since the neutrino is uncharged, it is the only particle in the universe that could be its own antiparticle. Understanding that would provide insight into why the neutrino has mass in the first place — information which would have wide-spread impacts in understanding how the universe was formed.

To determine if the neutrino is its own antiparticle, the researchers needed to observe a rare occurrence called neutrinoless double-beta decay. However, this process takes a single atom at least 1026 years — significantly longer than the age of the universe. Instead, they chose to observe nearly 1026 atoms over the course of six years.

To observe this incredibly rare decay, the researchers needed the perfect environment. In the Sanford Underground Research Facility in the Black Hills of South Dakota, located a mile underground, they built one of the cleanest and quietest environments on Earth. Extremely sensitive detectors were made of a high-purity germanium and were packed in a 50-ton lead shield and surrounded by materials of unprecedented cleanliness. Even the copper used was grown underground in their lab with impurity levels so low they couldn’t be measured.

Pettus and a team of IU students were responsible primarily for analyzing data from the experiment. Graduate student Nafis Fuad, undergraduate senior Isaac Baker, sophomore Abby Kickbush and Jennifer James, a student with the Research Experiences for Undergraduates Program, have been involved in the project. Their focus has been on understanding the stability of the experiment, analyzing details of the recorded waveforms and characterizing backgrounds.

“It’s like looking for a tiny needle in a very, very, very big haystack — you have to carefully get rid of all the hays (a.k.a. backgrounds) possible, and you don’t even know if there’s actually a needle in there in the first place or not,” Fuad said. “It’s very exciting to be a part of that search.”

While the researchers ultimately did not observe the decay they hoped for, they did discover that the neutrino’s scale for decay is longer than the limit they placed on it, which they will test further during the next phase of the experiment. In addition, they recorded other scientific results — ranging from dark matter to quantum mechanics — that helps provide a better understanding of the universe.

Through the project, the researchers proved that the techniques they utilized could be used at a much larger scale in a potentially game-changing search that could help explain the existence of matter in the universe.

“We didn’t see the decay we were looking for, but we have raised the bar on where to look for the physics we’re going after,” Pettus said. “True to its name, the Demonstrator advanced critical technologies that we are already leveraging for the next phase of the experiment in Italy. We may not have broken our picture of physics yet, but we’ve certainly pushed the horizons, and I am very excited about what we have accomplished.”

The next phase of the project, called LEGEND-200, has already begun taking data in Italy, with plans to run over the next five years. Researchers aim to observe the decay happening at a magnitude higher sensitivity than the Majorana Demonstrator. Beyond that, thanks to support from the U.S. Department of Energy, the team is already designing the successor experiment, LEGEND-1000.

Pettus is excited about the future of this work and looks forward to involving more students on the project, both in data analysis and hardware development for LEGEND-1000.

“If we discover the neutrino is its own antiparticle, there will still be ground under our feet and stars in the sky, and our understanding of physics doesn’t change the reality of the physical laws that always have and continue to govern our universe,” Pettus said. “But knowing what’s down there at the most fundamental level and how the universe works gives us a richer, more beautiful world to live in — or possibly just weirder — and that pursuit is fundamentally human.”

The Majorana Demonstrator was managed by Oak Ridge National Laboratory for the U.S. Department of Energy Office of Nuclear Physics, with support from the National Science Foundation.

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Vaping: Free e-cigarettes to be handed out in anti-smoking drive

Pregnant women will also be paid to quit smoking under government plans to be set out on Tuesday.

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Junior doctors’ strike puts patients at more risk – Barclay

The four-day walkout in England over pay comes after the Easter break when the NHS is already busy.

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Bowelbabe: Dame Deborah James, in her own words

‘You can’t leave things until tomorrow, because there might not be a tomorrow,’ said the cancer campaigner.

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New insights on brain development sequence through adolescence

Brain development does not occur uniformly across the brain, but follows a newly identified developmental sequence, according to a new Penn Medicine study. Brain regions that support cognitive, social, and emotional functions appear to remain malleable — or capable of changing, adapting, and remodeling — longer than other brain regions, rendering youth sensitive to socioeconomic environments through adolescence. The findings were published recently in Nature Neuroscience.

Researchers charted how developmental processes unfold across the human brain from the ages of 8 to 23 years old through magnetic resonance imaging (MRI). The findings indicate a new approach to understanding the order in which individual brain regions show reductions in plasticity during development.

Brain plasticity refers to the capacity for neural circuits — connections and pathways in the brain for thought, emotion, and movement — to change or reorganize in response to internal biological signals or the external environment. While it is generally understood that children have higher brain plasticity than adults, this study provides new insights into where and when reductions in plasticity occur in the brain throughout childhood and adolescence.

The findings reveal that reductions in brain plasticity occur earliest in “sensory-motor” regions, such as visual and auditory regions, and occur later in “associative” regions, such as those involved in higher-order thinking (problem solving and social learning). As a result, brain regions that support executive, social, and emotional functions appear to be particularly malleable and responsive to the environment during early adolescence, as plasticity occurs later in development.

“Studying brain development in the living human brain is challenging. A lot of neuroscientists’ understanding about brain plasticity during development actually comes from studies conducted with rodents. But rodent brains do not have many of what we refer to as the association regions of the human brain, so we know less about how these important areas develop,” said corresponding author Theodore D. Satterthwaite, MD, the McLure Associate Professor of Psychiatry in the Perelman School of Medicine at the University of Pennsylvania, and director of the Penn Lifespan Informatics and Neuroimaging Center (PennLINC).

To address this challenge, the researchers focused on comparing insights from previous rodent studies to youth MRI imaging insights. Prior research examining how neural circuits behave when they are plastic uncovered that brain plasticity is linked to a unique pattern of “intrinsic” brain activity. Intrinsic activity is the neural activity occurring in a part of the brain when it is at rest, or not being engaged by external stimuli or a mental task. When a brain region is less developed and more plastic, there tends to be more intrinsic activity within the region, and that activity also tends to be more synchronized. This is because more neurons in the region are active, and they tend to be active at the same time. As a result, measurements of brain activity waves show an increase in amplitude(or height).

“Imagine that individual neurons within a region of the brain are like instruments in an orchestra. As more instruments begin to play together in synchrony, the sound level of the orchestra increases, and the amplitude of the sound wave gets higher,” said first author Valerie Sydnor,a Neuroscience PhD student. “Just like decibel meters can measure the amplitude of a sound wave, the amplitude of intrinsic brain activity can be measured with functional MRI while kids are simply resting in the scanner. This allowed our team to study a functional marker of brain plasticity safely and non-invasively in youth.”

Analyzing MRI scans from more than 1,000 individuals, the authors found that the functional marker of brain plasticity declined in earlier childhood in sensory-motor regions but did not decline until mid-adolescence in associative regions.

“These slow-developing associative regions are also those that are vital for children’s cognitive attainment, social interactions, and emotional well-being,” Satterthwaite added. “We are really starting to understand the uniqueness of human’s prolonged developmental program.”

“If a brain region remains malleable for longer, it may also remain sensitive to environmental influences for a longer window of development,” Sydnor said. “This study found evidence for just that.”

The authors studied relationships between youths’ socioeconomic environments and the same functional marker of plasticity. They found that the effects of the environment on the brain were not uniform across regions nor static across development. Rather, the effects of the environment on the brain changed as the identified developmental sequence progressed.

Critically, youths’ socioeconomic environments generally had a larger impact on brain development in the late-maturing associative brain regions, and the impact was found to be largest in adolescence.

“This work lays the foundation for understanding how the environment shapes neurodevelopmental trajectories even through the teenage years,” said Bart Larsen, PhD, a PennLINC postdoctoral researcher and co-author.

Sydnor elaborated, “The hope is that studying developmental plasticity will help us to understand when environmental enrichment programs will have a beneficial impact on each child’s neurodevelopmental trajectory. Our findings support that programs designed to alleviate disparities in youths’ socioeconomic environments remain important for brain development throughout the adolescent period.”

This study was supported by the National Institute of Health (R01MH113550, R01MH120482, R01MH112847, R01MH119219, R01MH123563, R01MH119185, R01MH120174, R01NS060910, R01EB022573, RF1MH116920., RF1MH121867, R37MH125829, R34DA050297, K08MH120564, K99MH127293, T32MH014654). The study was also supported by the National Science Foundation Graduate Research Fellowship (DGE-1845298).

Additional support was provided by the Penn-CHOP Lifespan Brain Institute and the Penn Center for Biomedical Image Computing and Analytics.

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Early crop plants were more easily ‘tamed’

The story of how ancient wolves came to claim a place near the campfire as humanity’s best friend is a familiar tale (even if scientists are still working out some of the specifics). In order to be domesticated, a wild animal must be tamable — capable of living in close proximity to people without exhibiting dangerous aggression or debilitating fear. Taming was the necessary first step in animal domestication, and it is widely known that some animals are easier to tame than others.

But did humans also favor certain wild plants for domestication because they were more easily “tamed”? Research from Washington University in St. Louis calls for a reappraisal of the process of plant domestication, based on almost a decade of observations and experiments. The behavior of erect knotweed, a buckwheat relative, has WashU paleoethnobotanists completely reassessing our understanding of plant domestication.

“We have no equivalent term for tameness in plants,” said Natalie Mueller, assistant professor of archaeology in Arts & Sciences at Washington University. “But plants are capable of responding to people. They have a developmental capacity to be tamed.”

Her work with early indigenous North American crops shows that some wild plants respond quickly to clearing, fertilizing, weeding or thinning. Plants that respond in ways that make cultivation easier or more productive could be considered more easily tamed than those that cannot.

“If plants responded rapidly in ways that were beneficial to early cultivators — for example by producing higher yields, larger seeds, seeds that were easier to sprout, or a second crop in a single growing season — this would have encouraged humans to continue investing in the co-evolutionary relationship,” she said.

This capacity to express different traits and characteristics in response to the environment is called plasticity, and not all species are equally plastic.

“Some plants respond quickly and obviously to cultivation and care,” Mueller said. “I think ancient people would have noticed that they could double their yields just by thinning out dense stands of plants. This is one of the simplest and most common gardening techniques, but it has many important effects on the development of plants.”

What would an early farmer do?

Mueller’s study, published April 7 in PLOS ONE, focuses on work with a plant called erect knotweed, a member of the buckwheat family that was domesticated by indigenous farmers in eastern North America. The domesticated sub-species is now extinct; humans don’t eat it anymore. But Mueller and others have previously uncovered caches of seeds stored in caves, charred plant remnants in ancient hearths, and even the seeds of erect knotweed in human feces, clear evidence that this species was once consumed as a staple food.

Mueller, who studies lost crops, has spent years growing erect knotweed and other crop progenitors in experimental gardens, including at Washington University’s environmental field station, Tyson Research Center. She hasn’t always been successful with growing the plants she collects in the wild. In that way, Mueller can relate to the early farmers who similarly experimented with plants to discover their potential.

Her efforts have often been stymied by seed dormancy, a common feature among wild plants.

Unlike seeds you buy at the garden store, the seeds of most wild plants will not germinate if you simply sprinkle some water on them. Their requirements for germination are diverse and shaped by their evolutionary history. For example, if a plant has evolved in a place with a winter, like the Midwest, its seeds may not germinate unless they experience a long cold period. This prevents them from germinating too soon in the wild — they are waiting for spring. Domesticated plants have lost their diverse germination requirements.

The loss of germination inhibitors has presented a paradox to theorists of domestication. Many of the selective pressures that could have favored the evolution of this trait derive from planting seeds. But why would ancient people have started planting seeds if none of them germinated?

With erect knotweed, Mueller experienced a breakthrough of sorts. Based on four seasons of observations, Mueller determined that growing wild plants in the low-density conditions typical of a cultivated garden (i.e. spaced out and weeded) triggers plants to produce seeds that germinate more easily. This makes the harvests easier to plant successfully the next time around, eliminating a key barrier to further selection.

“Our results show that erect knotweed grown in low-density agroecosystems spontaneously ‘act domesticated’ in a single growing season, before any selection has occurred,” Mueller said.

Think of it as the plant equivalent to that first wolf who, though still a wild animal, sat down with its human friend around the fire. This is a behavioral shift, rather than an evolutionary one, but it allows new evolutionary pathways to open up.

A role for plant behavior

Mueller believes there is a bias in domestication studies toward viewing this changeability, or plasticity, as noise that is getting in the way of attempts to explain evolutionary change. Instead, this paper argues that we need to understand the development and behavior of wild crop relatives in order to explain the evolutionary process of domestication.

“Because we lack the practical experience with crop progenitors that ancient people had, these effects of the environment on plant development have gone mostly unnoticed and understudied,” Mueller said.

Her findings could have applications for developing new food crops: there is no reason why we have to be limited to the plants that our ancestors domesticated thousands of years ago.

Some researchers have been calling for de novo domestication — selecting wild plants with desirable characteristics and intentionally domesticating them. It may make sense to start looking to wild plants that are easily tamed as potential crops that could be developed for the future, Mueller said.

This paper also contributes to a growing awareness that plants are responsive and communicative beings. Though this idea is cutting-edge and hotly debated in biology and ecology, it is widespread in indigenous North American philosophies and probably would have been held by the people who domesticated erect knotweed and other plants thousands of years ago.

Recent research has shown how plants warn relatives about herbivores using chemical signaling, share resources through mycorrhizal networks and even emit noises when they are injured or stressed.

“You can’t explain plant domestication if you only consider the behaviors of humans, because domestication is the result of reciprocal relationships between multiple species that are all capable of responding to each other,” Mueller said.

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Novel immunotherapy agent safe, shows promise against high-risk prostate cancers

A new drug, a monoclonal antibody known as enoblituzumab, is safe in men with aggressive prostate cancer and may induce clinical activity against cancer throughout the body, according to a phase 2 study led by investigators at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy. If confirmed in additional studies, enoblituzumab could become the first promising antibody-based immunotherapy agent against prostate cancer.

In a clinical trial, 32 men with high-risk or very high-risk prostate cancers who were scheduled for prostate cancer surgery were treated with six weekly infusions of enoblituzumab prior to surgery, and were followed for an average of 30 months thereafter. Twenty-one patients, or 66%, had an undetectable prostate-specific antigen (PSA) level 12 months following surgery, suggesting that there was no sign of residual disease. Additionally, the drug was well-tolerated overall; no patients had any surgical delays or medical complications during or after the operation.

A description of the work was published April 3 in the journal Nature Medicine.

If enoblituzumab continues to perform well in further larger randomized studies, it could represent a new pathway for immunotherapy against multiple cancers, and the first one that may have a role for prostate cancer, says lead study author and cancer immunology researcher Eugene Shenderov, M.D., Ph.D., assistant professor of oncology at the Johns Hopkins University School of Medicine. Other existing antibody-based immunotherapy drugs have targeted immune checkpoints, natural on/off switches mediating immune responses, such as CTLA-4, PD-1 and LAG-3. Cancer cells hijack these checkpoints, turning off the immune response to cancer. “Drugs that block these checkpoints have had success in other types of cancers, including lung cancer and melanoma, but not in prostate cancer,” says Shenderov.

Enoblituzumab works by binding to a protein called B7-H3 that is overexpressed on prostate cancer cells and believed to impede the immune system’s ability to attack cancer cells. The new therapy could pack a one-two punch against cancer, Shenderov says, by blocking B7-H3’s inhibition of the immune system’s recognition and elimination of cancer cells, and also triggering a process called antibody-dependent cellular cytoxicity (ADCC), which leads to tumor cell destruction by activating additional immune cells such as macrophages and natural killer cells.

“Enoblituzumab appears safe and seems to activate the immune system in a way that involves both T-cells and myeloid cells,” Shenderov says. “What this means is if these results can be replicated in a larger, randomized study, it opens the possibility that combining this therapy with local, curative-intent therapies like surgical prostate removal or radiation therapy, would allow this drug to potentially kill micrometastatic disease hiding elsewhere in the body, and therefore prevent a significant number of men from experiencing recurring disease. That could be a paradigm shift in prostate cancer.”

The median age of study participants was 64 (age range 48-74). About half (47%) had a PSA greater than 10 ng/mL at diagnosis, which is abnormally high, and 50% had Gleason grade group 5 at biopsy, meaning they had highly aggressive disease. Patients were enrolled from February 2017 through June 2019. Enoblituzumab was confirmed to penetrate into prostate tumors and to bind to B7-H3 in the vast majority of participants, according to prostate samples studied after surgery.

Side effects of enoblituzumab were generally mild and included fatigue, neurological symptoms such as headache or dizziness, and flu-like or cold symptoms. One patient developed inflammation of the heart (myocarditis), which fully resolved with steroid treatment, and is a known side effect of other immune checkpoint drugs.

Beyond safety and anti-tumor activity based on PSA dropping to undetectable levels, investigators also looked for changes in the tumor microenvironment before and after enoblituzumab treatment. They found increased markers of cytotoxicity after treatment, consistent with the concept that the immune system was activated against tumor cells. The tumors showed increased infiltration with granulocytes, leukocytes and effector T-cells, and there was roughly a doubling of the density of cytotoxic T cells after treatment.

“The findings are exciting but exploratory, and need to be confirmed in larger study cohorts,” cautions senior study author Emmanuel S. Antonarakis, M.D., the Clark Endowed Professor of Medicine and director of GU Oncology for the University of Minnesota Masonic Cancer Center. Antonarakis was the senior investigator of the study while he was at the Johns Hopkins Kimmel Cancer Center.

“However, these results in high-risk prostate cancer patients, and the broader need for immunotherapeutic strategies with efficacy in prostate cancers, provide justification to further develop multipronged approaches that include targeting B7-H3 to optimize antitumor activity in prostate cancers and other solid malignancies,” he says.

Investigators are now planning a larger, randomized trial of enoblituzumab in newly diagnosed prostate cancer patients to assess clinical activity of the drug compared to current standards of care.

Coauthors of the current study were Angelo M. De Marzo, Tamara L. Lotan, Hao Wang, Sin Chan, Su Jin Lim, Hogkai Ji, Mohamad El Allaf, Carolyn Chapman, Samuel R. Denmeade, Kenneth J. Pienta, Christian P. Pavlovich, and Drew M. Pardoll of Johns Hopkins. Other study authors contributing to the paper were from MacroGenics Inc. of Rockville, Maryland (the maker of enoblituzumab); NanoString Technologies Inc. of Seattle; Adaptive Biotechnologies of Seattle; CDI Labs of Baltimore; the Northwestern University Feinberg School of Medicine in Chicago; and Charles G. Drake formerly at Johns Hopkins, who currently leads Immuno-Oncology at Janssen Research and Development.

The work was supported by the National Institutes of Health (Cancer Center Support Grant P30 CA006973), an NCI SPORE in Prostate Cancer (P50CA58236), a Prostate Cancer Foundation Young Investigator Award, the Department of Defense (grants W81XWH-16-PCRP-CCRSA and W81XWH-18-2-0015), and the Bloomberg~Kimmel Institute for Cancer Immunotherapy and by Macrogenics Inc, of Rockville, Maryland.

E. Shenderov is a paid consultant to GT Biopharma, Guidepoint Global, FirstThought, GLG, and receives institutional research funding from MacroGenics Inc., manufacturer of enoblituzumab. These relationships are managed by The Johns Hopkins University in accordance with its conflict of interest policies. E. Antonarakis has served as a paid consultant for Janssen, Astellas, Sanofi, Bayer, Bristol Myers Squibb, Amgen, Constellation, Blue Earth, Exact Sciences, Invitae, Curium, Pfizer, Merck, AstraZeneca, Clovis and Eli Lilly; and has received research support from MacroGenics, Janssen, Johnson & Johnson, Sanofi, Bristol Myers Squibb, Pfizer, AstraZeneca, Novartis, Curium, Constellation, Celgene, Merck, Bayer, Clovis and Orion. These relationships are managed by the University of Minnesota (Antonarakis’ current institution) in accordance with their conflict of interest policies.

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Junior doctors’ strike: NHS chief calls for Acas help with talks

Some 350,000 appointments and operations could potentially be cancelled this week, the NHS Confederation says.

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Engineered plants produce sex perfume to trick pests and replace pesticides

By using precision gene engineering techniques, researchers at the Earlham Institute in Norwich have been able to turn tobacco plants into solar-powered factories for moth sex pheromones.

Critically, they’ve shown how the production of these molecules can be efficiently managed so as not to hamper normal plant growth.

Pheromones are complex chemicals produced and released by an organism as a means of communication. They allow members of the same species to send signals, which includes letting others know they’re looking for love.

Farmers can hang pheromone dispersers among their crops to mimic the signals of female insects, trapping or distracting the males from finding a mate. Some of these molecules can be produced by chemical processes but chemical synthesis is often expensive and creates toxic byproducts.

Dr Nicola Patron, who led this new research and heads the Synthetic Biology Group at the Earlham Institute, uses cutting-edge science to get plants to produce these valuable natural products.

Synthetic biology applies engineering principles to the building blocks of life, DNA. By creating genetic modules with the instructions to build new molecules, Dr Patron and her group can turn a plant such as tobacco into a factory that only needs sunlight and water.

“Synthetic biology can allow us to engineer plants to make a lot more of something they already produced, or we can provide the genetic instructions that allow them to build new biological molecules, such as medicines or these pheromones,” said Dr Patron.

In this latest work, the team worked with scientists at the Plant Molecular and Cell Biology Institute in Valencia to engineer a species of tobacco, Nicotiana benthamiana, to produce moth sex pheromones. The same plant has previously been engineered to produce ebola antibodies and even coronavirus-like particles for use in Covid vaccines.

The Group built new sequences of DNA in the lab to mimic the moth genes and introduced a few molecular switches to precisely regulate their expression, which effectively turns the manufacturing process on and off.

An important component of the new research was the ability to fine tune the production of the pheromones, as coercing plants to continuously build these molecules has its drawbacks.

“As we increase the efficiency, too much energy is diverted away from normal growth and development,” explained Dr Patron.

“The plants are producing a lot of pheromone but they’re not able to grow very large, which essentially reduces the capacity of our production line. Our new research provides a way to regulate gene expression with much more subtlety.”

In the lab, the team set about testing and refining the control of genes responsible for producing the mix of specific molecules that mimic the sex pheromones of moth species, including navel orangeworm and cotton bollworm moths.

They showed that copper sulphate could be used to finely tune the activity of the genes, allowing them to control both the timing and level of gene expression. This is particularly important as copper sulphate is a cheap and readily-available compound already approved for use in agriculture.

They were even able to carefully control the production of different pheromone components, allowing them to tweak the cocktail to better suit specific moth species.

“We’ve shown we can control the levels of expression of each gene relative to the others,” said Dr Patron. “This allows us to control the ratio of products that are made.

“Getting that recipe right is particularly important for moth pheromones as they’re often a blend of two or three molecules in specific ratios. Our collaborators in Spain are now extracting the plant-made pheromones and testing them in dispensers to see how well they compare to female moths.”

The team hope their work will pave the way to routinely using plants to produce a wide range of valuable natural products.

“A major advantage of using plants is that it can be far more expensive to build complex molecules using chemical processes,” said Dr Patron. “Plants produce an array of useful molecules already so we’re able to use the latest techniques to adapt and refine the existing machinery.

“In the future, we may see greenhouses full of plant factories — providing a greener, cheaper and more sustainable way to manufacture complex molecules.”

The research is part of the SUSPHIRE project, which received support from ERACoBiotech funded by the Horizon 2020 research and innovation program and the UKRI Biotechnology and Biological Sciences Research Council (BBSRC).

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