In the past year, researchers at Rockefeller’s Laboratory of Bacteriology, headed by Luciano Marraffini, and at the MSKCC’s Structural Biology Laboratory, headed by Dinshaw Patel, have been studying key immune components of some CRISPR systems called CARF effectors. These newly discovered weapons take different approaches to achieving the same goal: arresting cellular activity, which prevents a virus from spreading through the rest of the bacterial population.

In a recent publication in Science, the scientists announce the newest CARF effector they’ve discovered, which they coined Cat1. Thanks to an unusually complex molecular structure, this protein can deplete a metabolite essential for cellular function. Left without fuel, the viral invader’s plans for a further onslaught are brought to a grinding halt.

“The collective work of our labs is revealing just how effective — and different — these CARF effectors are,” says Marraffini. “The range of their molecular activities is quite amazing.”

Multiple defense systems

CRISPR is a mechanism in the adaptive immune systems of bacteria and other certain single-cell organisms that offers protection against viruses, called phages. The six types of CRISPR systems work roughly the same way: A CRISPR RNA identifies foreign genetic code, which triggers a cas enzyme to mediate an immune response, often snipping off the invader material.

But an increasing body of evidence indicates that CRISPR systems deploy a wide variety of defensive strategies beyond genetic scissors. Marraffini’s lab has led the way on much of this research. In particular, they have been studying a class of molecules in CRISPR-Cas10 systems called CARF effectors, which are proteins that are activated upon phage infection of a bacterium.

CARF effector immunity is believed to work by creating an inhospitable environment for viral replication. For example, the Cam1 CARF effector causes membrane depolarization of an infected cell, while Cad1 triggers a sort of molecular fumigation, flooding an infected cell with toxic molecules.

Metabolic freeze

For the current study, the researchers wanted to try to identify additional CARF effectors. They used Foldseek, a powerful structural homology search tool, to find Cat1.

They found that Cat1 is alerted to the presence of a virus by the binding of secondary messenger molecules called cyclic tetra-adenylate, or cA₄, which stimulate the enzyme to cleave an essential metabolite in the cell called NAD⁺.

“Once a sufficient amount of NAD⁺ is cleaved, the cell enters a growth-arrest state,” says co-first author Christian Baca, a TPCB graduate student in the Marraffini lab. “With cellular function on pause, the phage can no longer propagate and spread to the rest of the bacterial population. In this way, Cat1 is similar to Cam1 and Cad1 in that they all provide population-level bacterial immunity.”

Unique complexity

But while its immune strategy may be similar to these other CARF effectors, its form is not, as co-first author Puja Majumder, a postdoctoral research scholar in the Patel Lab, revealed through detailed structural analysis using cryo-EM.

She found that the Cat1 protein has a surprisingly complex structure in which Cat1 dimers are glued by cA₄ signal molecule, forming long filaments upon viral infection, and trap the NAD⁺ metabolites within sticky molecular pockets. “Once the NAD⁺ metabolite is cleaved by Cat1 filaments, it’s not available for the cell to use,” Majumder explains.

But the protein’s singular structural complexity doesn’t stop there, she adds. “The filaments interact with each other to form trigonal spiral bundles, and these bundles can then expand to form pentagonal spiral bundles,” she says. The purpose of these structural components remains to be investigated.

Also unusual is the fact Cat1 often seems to work alone. “Normally in type III CRISPR systems, you have two activities that contribute to the immunity effect,” Baca says. “However, most of the bacteria that encode Cat1 seem to primarily rely on Cat1 for their immunity effect.”

Marraffini says these findings pose intriguing new questions. “While I think we’ve proven the big picture — that CARF effectors are great at preventing phage replication — we still have a lot to learn about the details of how they do it. It will be fascinating to see where this work leads us next.”

A new University of Arizona study, published in Nature Communications, describes a longer-lasting, 3D-printed, adhesive-free wearable capable of providing a more comprehensive picture of a user’s physiological state.

The device, which measures water vapor and skin emissions of gases, continuously tracks and logs physiological data associated with dehydration, metabolic shifts and stress levels.

“Wearable health monitoring traditionally depends on sensors that directly attach to the skin, but the skin itself constantly renews,” said Philipp Gutruf, an associate professor of biomedical engineering and member of the BIO5 Institute at the U of A who co-authored the study with lead author David Clausen, a doctoral student and researcher in the Gutruf Lab.

“This limits how long you can collect reliable data. With our sensor that tracks gaseous emissions from the skin, we overcome this constraint entirely,” Gutruf said.

Skin shedding weakens adhesives and clogs sensors, so wearables applied with adhesives must be reapplied every few days. Researchers in the Gutruf Lab at the U of A designed a device, worn on the forearm, that resembles a small 3D-printed cuff and can be worn continuously. The device sensors constantly measure gases emitted by the user, comparing their concentrations against normal outside air.

Unlike adhesive-based sports science and health monitoring wearables, which historically only record snapshots, the device developed by Gutruf and his colleagues delivers continuous, real-time data viewable on a smartphone or computer via secure Bluetooth.

“This opens an entirely new space of biomarkers,” said Gutruf. “For example, you can capture the metabolic signatures of exercise or stress without interrupting the subject’s normal routine. Previously, measurements of this kind required an entire room of equipment.”

Practical applications, proven results

With a device such as this, athletes can monitor hydration and exertion during training. The wearable could also record mental health and chronic disease symptoms to aid in prevention and treatment. In fact, tracking and monitoring physiological signs of stress in gas emissions can even help identify early metabolic disturbances, Gutruf said.

“Our design is stable even when exposed to everyday movement and environmental changes,” said Clausen. “We’re able to record data continuously over many days without recharge, all while capturing rich physiological data that isn’t typically possible in a wearable format or requires visible sweat.”

The researchers plan to expand the range of detectable biomarkers and integrate advanced data analytics to provide personalized health insights over even longer periods.

The research was funded by Arizona’s Technology and Research Initiative Fund, the Moore Foundation and with a discretionary award provided to Gutruf as the College of Engineering’s 2024 da Vinci Fellow.

The research, conducted by scientists at the University of Miami Rosenstiel School of Marine, Atmospheric, and Earth Science, in collaboration with scientists from The Shedd Aquarium, Coral Restoration Foundation, Reef Renewal, and Mote Marine Laboratory, provides timely insights into the thermal tolerance of elkhorn coral, a focal species for coral restoration efforts in Florida and currently listed under the Endangered Species Act.

The study, conducted in June 2022, one year before the unprecedented 2023 marine heatwave, tested 172 elkhorn coral colonies sourced from restoration nurseries stretching from Miami to the lower Florida Keys. Using custom-built rapid heat stress testing systems onboard the Shedd Aquarium’s research vessel, R/V Coral Reef II, researchers tested coral fragments under a range of temperature treatments to assess their heat tolerance.

Their findings showed that elkhorn corals hosting the heat-tolerant symbiont Durusdinium could survive short-term exposure to temperatures almost 2 ⁰C higher than those with the more common Symbiodinium. These resilient colonies were sexually derived juvenile corals that had acquired Durusdinium in Mote Marine Laboratory’s land-based facility on Summerland Key, providing evidence that manipulating symbiont communities in early life stages can be a very effective strategy for producing heat-tolerant corals for restoration.

“This study represents the most extensive thermal tolerance dataset gathered on A. palmata, revealing that, in Florida, the type of symbiotic algae a coral host, has a greater ability to increase heat resistance than environmental factors or genetic differences among different coral individuals,” said Richard Karp, the lead author of the study, who conducted the research while a doctoral student at the Rosenstiel School. “By incorporating novel interventions like heat-tolerant symbionts into restoration efforts, we can boost coral resilience and help restore this iconic species.”

The findings come at a critical time, as a global coral bleaching event — officially declared in 2024 — has already impacted 84 percent of the world’s reefs. The 2023 marine heatwave wiped out many remaining wild elkhorn colonies along Florida’s Coral Reef, underscoring the need for climate-resilient coral restoration strategies.

This study emphasizes the importance of scaling up symbiont-based interventions as part of current and future coral conservation and restoration work. By shifting coral-algal partnerships toward more thermally resilient symbionts, restoration practitioners may enhance the survival and long-term stability of coral populations in the face of increasing ocean temperatures.

“This is an example of Florida’s reef scientists sharing their scientific and restoration expertise and their coral nurseries, ships, and laboratories to make critical discoveries,” said Andrew Baker, a professor of marine biology and ecology at the Rosenstiel School and Karp’s doctoral advisor. “We need to continue to innovate and think outside the box to keep developing new approaches to help coral reefs in their fight for survival against continued warming and coral bleaching.”

Funding for the study was provided by National Oceanic and Atmospheric Administration-Coral Reef Conservation Program: NA20NMF4820289 and the Defense Advanced Research Projects Agency-Biological Technologies Office (DARPA): HR00112220041.

The authors include Richard F. Karp; Fabrizio Lepiz-Conejo, University of Miami Rosenstiel School of Marine, Atmospheric, and Earth Science; Shayle B. Matsuda and Bryce Corbett, Shedd Aquarium; Alexandra D. Wen, Joseph D. Unsworth, and Martine D’Alessandro, Rosenstiel School; Ken Nedimyer, Reef Renewal, USA; Amelia Moura, Coral Restoration Foundation; Erinn M. Muller and Zachary Craig, Mote Marine Laboratory; Diego Lirman, Rosenstiel School; Ross Cunning, Shedd Aquarium; and Andrew Baker, Rosenstiel School.

The study, led by the University of East Anglia (UEA), finds that as the ozone hole heals, its influence on the ocean carbon sink of the Southern Ocean will diminish, while the influence of greenhouse gas (GHG) emissions will rise.

Relative to its area, the Southern Ocean takes up a disproportionate amount of carbon, which reduces the radiative effects of carbon in the atmosphere and strongly mitigates human-caused climate change. Therefore, knowing how much carbon it will absorb, and what controls this carbon uptake, is important.

Scientists from the UEA and the National Centre for Atmospheric Science (NCAS), in the UK, looked at the relative role of ozone and GHG emissions in controlling the circulation of the Southern Ocean around Antarctica, focusing on how it would impact the carbon uptake.

They were interested in how the amount of atmospheric carbon taken up by the Southern Ocean has changed in the 20th century, and how it will change over the 21st century. Their findings are published today in the journal Science Advances.

Lead author Dr Tereza Jarníková, of the Tyndall Cente for Climate Change Research at UEA, said: “An interesting, and hopeful, highlight of this work is that the effects of human-caused ozone hole damage on the winds, circulation, and carbon uptake of the Southern Ocean are reversible, but only under a lower scenario of greenhouse gas emissions.”

The Southern Ocean takes up lots of atmospheric carbon because of its unique circulation and properties. Winds have intensified in past decades due to the loss of stratospheric ozone, acting to reduce the uptake of carbon.

As the ozone hole recovers, however, the study shows this phenomenon could reverse. At the same time, increasing GHG emissions could also lead to stronger winds, so how the Southern Ocean circulation will behave in the future, and therefore how much carbon this ocean will take up, is uncertain.

“We found that in the past decades, the depletion of ozone led to a relative reduction of the carbon sink, in general because of a tendency of the stronger winds to bring higher-carbon water from depth up to the surface of the ocean, making it less suitable for taking up atmospheric carbon,” said Dr Jarníková.

“This isn’t true in the future: in the future, the influence of ozone on the winds, and therefore on the Southern Ocean, diminishes, and it’s replaced by the increasing influence of greenhouse gas emissions, which also lead to strong winds.”

The study alsoshows that in the future, changes in ocean circulation will have less influence on carbon uptake than they had in the past, because of the changing distribution of carbon between the surface and the deep ocean.

The team used an Earth system model (UKESM1) to simulate three sets of ozone conditions for the time period 1950-2100: a world where the ozone hole never opened; a realistic world where the ozone hole opened but started healing following the adoption of the 1987 Montréal protocol that banned ozone depleting substances; and a world where the ozone hole persisted at its 1987 size throughout the 21st century.

They also simulated two future greenhouse gas scenarios: a low emissions scenario and a high emissions scenario, and then calculated how the main physical features of the ocean change over the 150 simulated years, as well as how the amount of carbon taken up by the ocean changes in response to these physical changes.

This work was funded by the UK Natural Environment Research Council and the Royal Society.

Many past studies have focused on reverse engineering to replicate the behavior of natural materials like bone, feathers and wood to reproduce their nonlinear responses to mechanical stress. A new study, led by the University of Illinois Urbana-Champaign civil and environmental engineering professor Shelly Zhang and professor Ole Sigmund of the Technical University of Denmark, looked beyond reverse engineering to develop a framework for programmable multilayered materials capable of responding to local disturbances through microscale interconnections.

The study findings are published in the journal Science Advances.

“This work was born out of a discussion with my collaborator, Professor Sigmund, about how we already can achieve some very extreme behaviors, but there’s always a physical limit or upper bound that single materials can achieve, even with programming,” Zhang said. “That led us to consider what kind of engineering could enable some of the crazy material behaviors needed in real life. For example, extreme buckling behaviors could help dissipate energy for things like car bumpers.”

That is when the team turned their attention to biological materials with multiple layers serving a different purpose, and how they could fabricate a synthetic material and use internal, microscale programming and optimization to control its response to mechanical stress and strain.

“We landed on the idea to design multilayered materials with each layer being capable of exhibiting different properties and behaviors,” Zhang said.

But not stopping there, the team pushed themselves to include the ability of individual layers to collaborate to essentially behave collectively as one.

“Our new framework presents several advantages over existing methodologies for nonlinear stress-strain responses,” Zhang said. “It optimizes nacre-like multiple layers along with their interconnections in a continuum setup, which significantly expands the design space compared to similar work involving a single-layer setup or lattice structures.”

During fabrication, the team learned some lessons. The theoretical idea behind this work is to have an infinitely periodic material. Still, the team must fabricate finite units, and it was to be expected that the theoretical material and the actual fabricated material would exhibit different behaviors.

“The discrepancy we found is something that will always happen in real life,” Zhang said. “But we can harness this information to intentionally program the sequence of the buckling of each of the individual cells in assembly, store some information inside, and then later we can decode the information. It was fascinating to capture this discrepancy and for it to end up providing information needed to improve the work.”

There is still a lot of work to be done to scale up fabrication for this type of material, but Zhang said that one valuable thing learned from this study is that when people collaborate, they achieve much greater things.

“I think it works the same for materials,” Zhang said. “When different materials collectively work together, they can do things that are much more impactful than if they do things individually.”

Zhang also is affiliated with mechanical science and engineering and the National Center for Supercomputing Applications at Illinois.