Category: 7. Science

NASA has revealed the most detailed images yet taken of comet 3I/ATLAS, the interstellar visitor that is currently barreling its way through our solar system.

The images, taken by NASA’s Hubble Space Telescope, have enabled astronomers to more accurately estimate the space object’s size — and it looks like it’s smaller than we thought, NASA said in a statement.

A Planet Reduced to Dust

BD+05 4868 b belongs to a rare category of extrasolar planets known as disintegrating exoplanets. These worlds are so close to their host stars that their surfaces melt and evaporate, creating vast clouds of dust. This particular exoplanet orbits its star every 30.5 hours at a distance of just 0.02 astronomical units (AU), twenty times closer than Mercury orbits our Sun.

The host star is a K-type main-sequence star, a dwarf star approximately 30% smaller and 1,000°C cooler than the Sun. Its age is estimated at roughly twice that of the Sun, making the presence of a rapidly vaporizing planet all the more scientifically intriguing.

Current observations indicate that BD+05 4868 b likely possesses a small solid body, possibly similar in size to Mercury or even Earth’s Moon. However, what dominates its observational profile is an enormous dust tail – a feature more commonly associated with comets. This tail is so extensive that it covers half of the planet’s orbit, dramatically reducing the star’s brightness during transit.

The Science of Planetary Vaporization

The intense proximity to its star exposes BD+05 4868 b to extreme temperatures capable of melting rock. According to Dr. Hon, the planet loses material at a rate equivalent to the mass of Mount Everest during every orbit. This material is ejected as silicate vapor, which subsequently cools and condenses into dust, forming the distinctive tail.

Unlike more massive planets that can maintain their atmospheres due to stronger surface gravity, BD+05 4868 b is believed to be low-mass. This weak gravitational hold allows vaporized material to escape more easily, driving the rapid rate of disintegration. While ultra-short-period planets are not uncommon, only four, including BD+05 4868 b, have been confirmed to possess active dust tails.

A Unique Opportunity for Planetary Composition Analysis

What makes this discovery invaluable is the potential to analyze the planet’s internal composition. The dust tail, composed of evaporated material from the planet’s surface, may contain minerals from the crust, mantle, or even core. According to Dr. Hon, this offers a rare observational window into the internal structure of a distant world.

Spectroscopic analysis, particularly using transmission spectroscopy (the study of starlight filtered through a planet’s atmosphere or tail), could reveal the mineralogical makeup of the disintegrating material. Such studies can provide insights into the planet’s geological history and formation processes.

Preparing for Follow-Up Observations

One reason BD+05 4868 b represents an exceptional target for follow-up studies is its brightness. Discovered by TESS, which focuses on relatively nearby stellar systems, the planet’s host star is significantly brighter than those of previously known disintegrating exoplanets, all of which were discovered by the Kepler mission. This increased brightness enables higher-quality data collection and detailed spectroscopic studies.

Future observations with the James Webb Space Telescope (JWST) and ground-based telescopes are already planned. These investigations will focus on determining the composition of the dust tail and constraining the planet’s mass through radial velocity measurements, which track the subtle movements of the star caused by the gravitational pull of the orbiting planet.

The Broader Implications

Beyond its individual significance, BD+05 4868 b raises broader questions about the evolution of planetary systems. As Dr. Hon noted, the mechanism by which such a planet migrates into a death spiral orbit remains an open question. Possibilities include gravitational perturbations from other planets or companion stars.

The discovery also suggests that additional disintegrating exoplanets may be awaiting identification within existing datasets. Understanding these worlds could transform our knowledge of planetary lifecycles and the diverse outcomes of planetary system evolution.

BD+05 4868 b offers a unique laboratory for observing planetary destruction in real-time. Its discovery demonstrates the power of large-scale survey missions, such as TESS, and highlights the importance of diligent data analysis.

Watch the full SETI Live conversation here, and read the research paper here.

A previously unknown Jurassic sea reptile has been uncovered from Germany’s renowned Posidonia Shale fossil beds. The discovery sheds new light on the oceans around about 183 million years ago.

Scientists at the Naturkunde‑Museum Bielefeld, working with colleagues from the Polish Academy of Sciences, examined a nearly complete skeleton that has preserved traces of soft tissue.

Sea creature with distinctive features

While unearthed back in 1978 from Holzmaden quarry, the distinctive aspects of the fossil have been overlooked.

“This specimen has been in collections for decades, but previous studies never fully explored its distinctive anatomy,” said Sven Sachs, lead author of the study.

“Our detailed examination revealed an unusual combination of skeletal features that clearly distinguish it from all previously known plesiosaurs.”

The species has been named Plesionectes longicollum, which translates to long‑necked near‑swimmer.” The creature represents a new species within the plesiosauroid group – a lineage of long‑necked marine reptiles that sailed Earth’s seas during the age of dinosaurs.

Despite representing an immature individual, the fossils’ anatomical traits were pronounced enough to confirm a new genus and species.

What are plesiosaurs?

Plesiosaurs were marine reptiles that lived during the time of the dinosaurs. They first appeared in the Late Triassic and became especially common in the Jurassic period. These animals lived in oceans all over the world and could grow to impressive sizes.

There are two major body types among plesiosaurs. Some had small heads, long necks, and wide bodies with four flippers – like the newly identified Plesionectes longicollum.

Others had shorter necks, larger heads, and strong jaws built for powerful bites. Both types were excellent swimmers, using their flippers to glide through water in a motion similar to underwater flying.

They likely fed on fish, squid, and other small marine creatures. Their fossils have been found on every continent, which shows how widespread they were.

Despite their success, plesiosaurs eventually went extinct at the end of the Cretaceous period – around the same time as the dinosaurs.

This makes every new discovery, like Plesionectes longicollum, important for understanding how these animals lived, evolved, and fit into ancient ocean ecosystems.

Insights from the Jurassic reptile

This reptile is now the oldest known plesiosaur from the Holzmaden region. The study shows that the Posidonia Shale holds even more diversity than scientists realized.

Although other plesiosaurs have been found in the same formation – five in total from all three major plesiosaur lineages – this new specimen reveals yet another branch on the family tree of Jurassic marine life.

“This discovery adds another piece to the puzzle of marine ecosystem evolution during a critical time in Earth’s history,” explained Dr. Daniel Madzia of the Polish Academy of Sciences.

“The early Toarcian period when this animal lived was marked by significant environmental changes, including a major oceanic anoxic event that affected marine life worldwide.”

Why fossils like this still matter

Uncovering a new species is always exciting – but what makes the Plesionectes longicollum fossil even more remarkable is how it reminds us that science is always evolving.

Museum collections everywhere contain thousands of specimens that were tagged, shelved, and perhaps forgotten for years. As instrumentation improves and new questions are asked, these old discoveries can gain new significance.

Re-examining fossils with modern techniques allows scientists to spot differences that might have been missed before.

In this case, those differences were enough to rewrite part of the plesiosaur family tree. The research shows how much we still have to learn – not just from new digs, but from existing collections.

Fossils like this one offer more than a glimpse into extinct species – they provide insight into how life adapted to past climate shifts, ocean changes, and extinction events. Ultimately, they help scientists better anticipate how modern ecosystems might respond to the environmental challenges we face today.

The Plesionectes longicollum fossil – catalogued as specimen SMNS 51945 – is on permanent display at the Staatliches Museum für Naturkunde Stuttgart (Stuttgart State Museum of Natural History).

The full study was published in the journal PeerJ.

Image Credit: Peter Nickolaus

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Krikalev grew up in Leningrad (which he effectively watched become St Petersburg from space) and obtained a mechanical engineering degree before going to work as a rocket engineer at NPO Energia, where, among other projects, he worked as part of the rescue team when the Salyut 7 space station failed in 1985. Shortly thereafter, he was selected as a cosmonaut and spent years in training, working on everything from repairing the space station to conducting spacewalks. 

Unfortunately, his training didn’t incorporate what to do when you are left in space with no official space organization (or country), which on his 1991 mission aboard Mir would have been much more useful.

The trip started off badly. As the spacecraft carrying Krikalev and two others approached Mir the targeting system failed, meaning Krikalev had to dock manually, with any wrong move being potentially fatal. Keeping a cool head, he docked and the cosmonauts – plus the first British astronaut Helen Sharman – climbed on board. 

Krikalev loved being on Mir, which was incredibly fortunate. As well as seeing Earth from the viewing port, he loved “the sense of freedom which you experience in weightlessness,” he told The Guardian in 2015. “[Y]ou feel like a bird that is able to fly!”

He performed his duties as normal, while below the Soviet Union began to strain further and crack. News did reach them on Mir, but it was sparse.

“It was a long process and we were getting the news, not all at once, but we heard about the referendum, for example,” Krikalev explained. “I was doing my job and was more worried about those on the ground – our families and friends – we had everything we needed!”

Soon, even the space station was affected by the politics going on 358 kilometers (222 miles) below. With Kazakhstan (among others) pushing for independence, Soviet President Mikhail Gorbachev announced that a Kazakh cosmonaut would board Mir in order to appease the government.

Though not as much was known about the effects of extended stays in space then, Krikalev was aware of some of the risks of staying on Mir for so long.

“Do I have enough strength? Will I be able to readjust for this longer stay to complete the program?” Krikalev reportedly posed in an interview with Russian media. “Naturally, at one point I had my doubts.”

In October 1991, the Soyuz TM-13 mission arrived at Mir. This unorthodox mission carried Soviet commander Alexander Volkov and Kazakh cosmonaut Toktar Aubakirov, along with Austrian astronaut Franz Viehböck. The presence of Aubakirov, the first person from Kazakhstan to go to space, was used as a tool to persuade the then-Kazakh SSR to continue hosting launches from Baikonur Cosmodrome. 

However, neither Aubakirov nor Viehböck had been extensively trained and were not prepared for long-duration Mir operations, meaning they could not replace Krikalev as a flight engineer. After their short stay of just over one week, they returned to Earth with the departing crew, leaving Krikalev and fellow Soviet Volkov. 

Small and claustrophobic as well as high above Earth, Mir probably wasn’t the best place to be with very little company. It was invariably described as a “death trap” that was “held together by baling wire, duct tape, and healthy doses of WD-40,” as well as “derelict” and a “lemon”. In terms of things you’d rather be stranded in, a derelict oiled-up lemon isn’t exactly top of the list.

Then, on December 25, 1991, the Soviet Union finally collapsed. With the collapse, there was even less money for a mission that would relieve Krikalev of his duties. If all else failed, there was the Soyuz capsule that could be used to escape, though this could mean sacrificing the space station.

“The strongest argument was economic because this allows them to save resources here,” Krikalev said while still on Mir. “They say it’s tough for me – not really good for my health. But now the country is in such difficulty, the chance to save money must be top priority.”

Deals were struck between America and Russia, gaining the funding needed to send more cosmonauts and astronauts into orbit. On March 25, 1992, having spent a then-record 311 consecutive days in space, Krikalev finally returned to Earth along with Volkov and a German astronaut called Klaus-Dietrich Flade.

When Krikalev and Volkov had left Earth, they had been citizens of a state that now no longer existed, earning them the nickname of the “last Soviet citizens.”

Despite spending a lot more time in space than he’d intended, Krikalev went straight back to training upon his return, and ended up clocking up 803 days in space, breaking previous records for time spent above the Earth. In calculations by Universe Today, thanks to relativity and time dilation, he has traveled into the future by a whopping 0.2 seconds.

He went into space as a Soviet citizen and came down in a different state, in a different time to everyone else around him.

A previous version of this story was published in September 2020.

Look inside a brain cell with Huntington’s disease or ALS and you are likely to find RNA clumped together.

These solid-like clusters, thought to be irreversible, can act as sponges that soak up surrounding proteins key for brain health, contributing to neurological disorders.

How these harmful RNA clusters form in the first place has remained an open question.

Now, University at Buffalo researchers have not only uncovered that tiny droplets of protein and nucleic acids in cells contribute to the formation of RNA clusters but also demonstrated a way to prevent and disassemble the clusters.

Their findings, described in a study published recently in Nature Chemistry, uses an engineered strand of RNA known as an antisense oligonucleotide that can bind to RNA clusters and disperse them.

“It’s fascinating to watch these clusters form over time inside dense, droplet-like mixtures of protein and RNA under the microscope. Just as striking, the clusters dissolve when antisense oligonucleotides pull the RNA aggregates apart,” says the study’s corresponding author, Priya Banerjee, PhD, associate professor in the Department of Physics, within the UB College of Arts and Sciences. “What’s exciting about this discovery is that we not only figured out how these clusters form but also found a way to break them apart.”

The work was supported by the U.S. National Institutes of Health and the St. Jude Children’s Research Hospital.

How RNA clusters form

The study sheds new light on how RNA clusters form within biomolecular condensates.

Cells make these liquid-like droplets from RNA, DNA and proteins — or a combination of all three. Banerjee’s team has researched them extensively, investigating their role in both cellular function and disease, as well as their fundamental material properties that present new opportunities for synthetic biology applications.

The condensates are essentially used as hosts by repeat RNAs, disease-linked RNA molecules with abnormally long strands of repeated sequences. At an early timepoint, the repeat RNAs remain fully mixed inside these condensates, but as the condensates age, the RNA molecules start clumping together, creating an RNA-rich solid core surrounded by an RNA-depleted fluid shell.

“Repeat RNAs are inherently sticky, but interestingly, they don’t stick to each other just by themselves because they fold into stable 3D structures. They need the right environment to unfold and clump together, and the condensates provide that,” says the study’s first author, Tharun Selvam Mahendran, a PhD student in Banerjee’s lab.

“Crucially, we also found that the solid-like repeat RNA clusters persist even after the host condensate dissolves,” Mahendran adds. “This persistence is partly why the clusters are thought to be irreversible.”

Preventing — and reversing — clusters

The team was first able to demonstrate that repeat RNA clustering can be prevented by using an RNA-binding protein known as G3Bp1 that is present in cells.

“The RNA clusters come about from the RNA strands sticking together, but if you introduce another sticky element into the condensate, like G3BP1, then the interactions between the RNAs are frustrated and clusters stop forming,” Banerjee says. “It’s like introducing a chemical inhibitor into a crystal-growing solution, the ordered structure can no longer form properly. You can think of the G3BP1 as an observant molecular chaperone that binds to the sticky RNA molecules and makes sure that RNAs don’t stick to each other.”

In order to reverse the clusters, the team employed an antisense oligonucleotide (ASO). Because ASO is a short RNA with a sequence complementary to the repeat RNA, it was able to not only bind to the aggregation-prone RNAs but also disassemble the RNA clusters.

The team found that ASO’s disassembly abilities were highly tied to its specific sequence. Scramble the sequence in any way, and the ASO would fail to prevent clustering, let alone disassemble the clusters.

“This suggests our ASO can be tailored to only target specific repeat RNAs, which is a good sign for its viability as a potential therapeutic application,” Banerjee says.

Banerjee is also exploring RNA’s role in the origin of life, thanks to a seed grant from the Hypothesis Fund. He is studying whether biomolecular condensates may have protected RNA’s functions as biomolecular catalysts in the harsh prebiotic world.

“It really just shows how RNAs may have evolved to take these different forms of matter, some of which are extremely useful for biological functions and perhaps even life itself — and others that can bring about disease,” Banerjee says.

Understanding how atoms behave has led to many advances, including PET scans that diagnose disease and nuclear energy that powers homes. But our picture of the nucleus, the heart of the atomic world, is still incomplete. Researchers plan to improve our understanding with an advanced new instrument: GRETA, the Gamma-Ray Energy Tracking Array.

The project team, led by the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), has now completed construction of GRETA’s key components: multiple germanium detector modules, the electronics system, the instrument’s mechanical frame and infrastructure, and the computing systems. The team includes scientists and engineers from Berkeley Lab’s nuclear science, engineering, and computing divisions; Michigan State University (MSU); and Argonne and Oak Ridge national laboratories.

“Our goal was to make the best high-resolution, high-efficiency gamma-ray detector we possibly could, so we can answer big questions about the nature of matter and fundamental forces,” said Paul Fallon, GRETA’s project director. “With every advance in this technology, we can improve our resolving power and can see weaker and weaker structures. GRETA will be 10 to 100 times more sensitive than previous nuclear science experiments.”

GRETA was assembled at Berkeley Lab and is now ready to ship to the Facility for Rare Isotope Beams (FRIB), a DOE Office of Science user facility at MSU. There, researchers will install and commission the device, adding additional detector modules as they become available. GRETA is built for flexibility as well as sensitivity, and will move to different stations at FRIB (and later Argonne) to use particle beams of different types and energies.

To get a glimpse inside the nucleus, researchers will smash a particle beam into a target placed at the center of GRETA, briefly creating energetic, rare atoms. GRETA’s sensitive germanium detectors measure the 3D paths and energies of emitted gamma rays, particles of light made as an excited atom returns to a more stable state. That data can reveal all sorts of interesting insights.

This timelapse video shows the construction and testing of GRETA at Berkeley Lab. (Credit: GRETA collaboration)

For example, researchers can probe the structure of rare and short-lived isotopes, atoms with different numbers of neutrons compared to the more common versions of the elements. FRIB will be able to create and study more than 1,000 new isotopes. Scientists can also test the limits of how many protons and neutrons a nucleus can hold, exploring “the drip lines,” the point beyond which neutrons or protons can no longer bind within the nucleus and instead “drip” away.

Other experiments will study pear-shaped nuclei, a way to search for subtle violations of fundamental symmetries in nature and explore why our universe is made mostly of matter (instead of antimatter). Researchers will also use GRETA to shed light on the processes within stars that forge elements heavier than iron.

“Gamma-ray spectroscopy is among our most powerful tools to learn about the fundamental nature of the atomic nucleus,” said Heather Crawford, a scientist at Berkeley Lab and deputy project director for GRETA. “The excited states and gamma rays are a fingerprint for each isotope. GRETA is the world’s most powerful microscope to examine these fingerprints and answer questions about the nucleus and the forces that govern it.”

A Sphere of Germanium Crystals

GRETA is an expansion of an earlier project, GRETINA, that used 12 germanium detector modules to capture gamma rays. GRETA will bring the total to 30 modules, completing a full sphere around the target and vastly increasing the instrument’s tracking capabilities. By catching more gamma rays, researchers will get a more accurate picture of what’s happening in the nucleus – and more quickly.

Each detector module is made of four tapered hexagonal crystals of ultra-pure germanium roughly the size of a 10-ounce coffee cup. The germanium crystals are such specialized and difficult pieces to make, only about four detector modules can be produced every year. Once tightly packed together and cooled to cryogenic temperatures (around negative 300 degrees Fahrenheit), the crystals are exceptionally good at measuring the energy and position of gamma rays, enabling researchers to reconstruct their interactions in the crystal.

GRETA’s backbone is a complex, meter-wide aluminum frame that supports the germanium detectors and electronics. The sphere is built in two halves that separate, opening space for researchers to change out targets at the center of the instrument. To make sure the sphere comes back together seamlessly, the base plate and rails are aligned within one millionth of an inch. Each half can also rotate, allowing researchers to safely install the detector modules before moving them into their final orientation for operations. The team put the support assembly through its paces with dummy weights last year before beginning integration of the other components.

Fastest Gamma-Ray Detector in the West

A key part of the project was to design compact and efficient new electronics and a dedicated computing system for GRETA. The new electronic system can perform with up to 50,000 signals per second in each crystal, and a dedicated computing cluster will process up to 480,000 gamma-ray interactions every second in real time. Tests this spring showed GRETA surpassing its design goal, processing as many as 511,000 gamma-ray interactions per second.

GRETA is also a potential first use case for an accelerated data pipeline called DELERIA, a new software platform for streaming enormous amounts of data at high speeds. Researchers will be able to transfer data through DOE’s high-speed network, ESNet, to be crunched at supercomputing facilities off-site and returned almost immediately. That rapid feedback will help researchers optimize their experiments as they take place even without a dedicated computing cluster.

GRETA will incorporate GRETINA’s detector modules and replace the instrument as the flagship gamma-ray detector at FRIB. The project team will ship the instrument to FRIB this summer, with installation expected in the fall and first experiments to begin in 2026.

Fatty diets and obesity affect the structure and function of astrocytes¹, the star-shaped brain cells located in the striatum, a brain region involved in the perception of pleasure generated by food consumption. What is even more surprising is that by manipulating these astrocytes in vivo in mice can influence metabolism and correct certain cognitive changes associated with obesity (ability to relearn a task, for example). These results, described by scientists from the CNRS² and the Université Paris Cité, were recently published in the journal Nature Communication.

Our brains glow. We can’t see it happen with the naked eye, but scientists can measure extremely subtle light passing through the skull – and a recent study has found that this light changes depending on what we’re doing.

All living tissue emits a faint light called ultraweak photon emissions (UPE). This light extinguishes when the tissue dies. However, the human brain produces a significant amount of UPE due to the high energy it consumes (the brain accounts for approximately 20 per cent of the body’s total energy).

“Ultraweak photon emissions, or UPE, are very weak light signals – trillions of times weaker than a light bulb – that are generated by cells of all kinds throughout the body,” senior author Dr Nirosha Murugan, assistant professor of health sciences at Wilfrid Laurier University, in Ontario, Canada, told BBC Science Focus.

“Even though UPEs are very weak signals, the brain’s energy consumption makes it a great generator of light relative to other organs,” she said. “Imagine hundreds of billions of brain cells, each individually generating weak light signals, but with a collective glow that we can measure outside the head.”

Murugan’s team wanted to investigate whether this glow changed depending on what the brain was doing, to see if scientists could use it to measure brain activity.

So, they recruited 20 adults to sit in a dark room while the scientists measured electrical signals – using a cap fitted with electricity sensors – as well as light emitted from their brains.

Participants were instructed to carry out simple instructions, involving opening and closing their eyes, and listening to sound recordings.

The scientists then compared the electrical signals and UPEs that they recorded – and found a correlation.

“We discovered that light signals detected around the head were related to the brain’s electrical activity during cognitive tasks,” said Murugan. “These light emission patterns from the brain are constantly changing. They oscillate, are complex and carry information.”

The brains emitted this light in slow rhythmic patterns, at a frequency slower than once per second, that seemed to steady over the course of each two-minute task.

Murugan said that measuring this brain light could “change the field of neuroscience” by giving scientists and doctors new ways to scan the brain, to potentially find signs of disorders such as epilepsy, dementia or depression.

This light could even be playing a role inside our brains, rather than just being a byproduct of its function. Murugan said that studying it could “reveal a hidden dimension” of the inner workings of our minds.

“We hope the prospect of detecting and deciphering light signals from the brain will inspire new questions that were previously unthinkable,” she said. “For example, because UPEs travel through the skull, could they possibly influence other brains in the environment?”

This was only a small, preliminary study, so there is still a lot for scientists to discover when it comes to UPEs in the brain.

But Murugan said she hoped her team’s findings would “initiate new conversations about the role of light in brain function.”

Read more:

About our expert

Dr Nirosha Murugan is an assistant professor in the Department of Health Sciences at Wilfrid Laurier University in Ontario, Canada. She was recently appointed as a Tier 2 Canada Research Chair in Biophysics from Algoma University, also in Ontario.

Fighting off pathogens is a tour de force that must happen with speed and precision. A team of researchers at CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, and at Medical University of Vienna (MedUni Vienna) has investigated how macrophages master this challenge.

Led by Christoph Bock, PhD, CeMM principal investigator and professor at MedUni Vienna, and Matthias Farlik, PhD, principal investigator at the MedUni Vienna, the researchers’ newly reported study offers a time-resolved analysis of the molecular processes that unfold when macrophages encounter various pathogens and infection-linked stimuli. To achieve this, the team developed a new method in mice that combines CRISPR gene editing and machine learning, and which identified key regulators of macrophage responses to the six different stimuli, including infectious pathogens, pathogen-derived stimuli, and pro-inflammatory cytokines.

“This study combined epigenome and transcriptome time series profiling with high-content CRISPR screening and integrative computational analysis in order to dissect the pathogen response in murine macrophages,” the team wrote in their paper in Cell Systems, which is titled “Integrated time-series analysis and high-content CRISPR screening delineate the dynamics of macrophage immune regulation.” They further concluded, “To our knowledge, this is the first study that combines epigenome/transcriptome time-series profiling with high-content CRISPR screening, demonstrated here for the dissection of gene regulation in mouse macrophages.”

“Innate immunity is critical for protecting the body against pathogens,” the authors wrote. “Macrophages are among the first immune cells to respond to invading pathogens, which they sense via pattern recognition receptors.”

Macrophages are also messengers, releasing various signals to recruit other immune cells, triggering inflammation, and presenting digested fragments of pathogens on their surface, guiding the adaptive immune system to develop long-term immunity. Macrophages encountering a pathogen are under immense pressure. If they react too late or not decisively enough, an infection may become fatal. But an overshooting immune response is equally damaging. Within a very short time, a tailored immune response must be initiated, including cascades of biochemical reactions triggered, thousands of genes activated, and an arsenal of substances produced—each response tailored to the specific pathogen encountered.

The authors further explained in their paper, “Detection of pathogen-associated molecular patterns (PAMPs) activates signaling cascades and transcriptional regulators such as NF-κB, IRF, and AP-1. These regulatory proteins orchestrate expression of their target genes over the course of the pathogen response and during the subsequent return to homeostasis.”

To understand how macrophages coordinate this multitude of tasks, Bock, Farlik and colleagues exposed murine macrophages to various immune stimuli that mimic bacterial or viral infections. They tracked the changes inside the cells by measuring gene activity and DNA accessibility every few hours, establishing a molecular timeline of how the regulatory programs unfold step by step.

Next, the team identified regulatory proteins that orchestrate these programs, using CRISPR genome editing to produce hundreds of gene knockouts, and single-cell RNA sequencing to characterize the genetically perturbed cells. “We investigated six immune stimuli (Listeria, LCMV, Candida, LPS, IFN-β, and IFN-γ) over a dense multiomics time course and performed high-throughput functional dissection of the macrophage response to Listeria using a combined CROP-seq and CITE-seq method,” they wrote.

This innovative method uncovered a network of several dozen regulators that share the responsibility of triggering the most appropriate immune response. The identified regulators include many that would be expected, such as the JAK-STAT signaling pathway, but also identified splicing factors and chromatin regulators that may have far less well understood roles in immune regulation. “We identified new roles of transcription regulators such as Spi1/PU.1 and JAK-STAT pathway members in immune cell homeostasis and response to pathogens,” the investigators commented. “Macrophage activity was modulated by splicing proteins SFPQ and SF3B1, histone acetyltransferase EP300, cohesin subunit SMC1A, and mediator complex proteins MED8 and MED14.”

Senior author Bock said, “It is impressive how much complexity there is in this ancient part of our immune system, which we share with sponges, jellyfish, and corals. Thanks to the advances in CRISPR screening technology, we can systematically study the underlying regulatory programs.”

In their paper the team stated in summary, “…this study establishes a time-resolved regulatory map of pathogen response in macrophages, and it describes a broadly applicable method for dissecting immune-regulatory programs through integrative time-series analysis and high-content CRISPR screening.”