Toronto researchers devise new way to find proteins for targeted treatment of disease

Method interrogates entire human proteome for effector proteins, which influence stability of other proteins via induced proximity

UNIVERSITY OF TORONTO

 

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PROFESSOR MIKKO TAIPALE

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CREDIT: UNIVERSITY OF TORONTO

Researchers at the University of Toronto and Sinai Health have created a new platform to identify proteins that can be co-opted to control the stability of other proteins — a new but largely unrealized approach to the treatment of disease.

The researchers developed a method to interrogate the entire human proteome for ‘effector’ proteins, which can influence the stability of other proteins via induced proximity. The study marks the first time researchers have searched for effector proteins on this scale, and has identified many new effectors that could be used therapeutically.

“We found more than 600 new effector proteins in 14,000 genes,” said Juline Poirson, first author on the study and visiting scientist at U of T’s Donnelly Centre for Cellular and Biomolecular Research. “Over 200 of the new effectors can efficiently degrade their target proteins, while about 400 effectors were capable of stabilizing, and thereby increasing the abundance of, an artificial target protein.”

The study, which involved researchers at Sinai Health’s Lunenfeld-Tanenbaum Research Institute, was published in the journal Nature.

“Targeting proteins through induced proximity is a new and promising area of biomedical research,” said Mikko Taipale, principal investigator on the study and an associate professor of molecular genetics at the Donnelly Centre and the Temerty Faculty of Medicine. “Not only did we find new effectors worth further investigation for drug discovery, we developed a synthetic platform that can be used to conduct unbiased, proteome-wide, induced-proximity screens to continue expanding the library of effector proteins.”

The effectors currently in use for targeted protein degradation and stabilization are E3 ubiquitin-ligases (E3s) and deubiquitinases (DUBs), respectively. E3 is an enzyme that transfers the ubiquitin molecule to the target protein, which essentially flags the protein for a proteosome to digest it. On the other hand, a DUB enzyme removes the ubiquitin tag from a protein, thereby preventing the protein from being recognized and degraded by a proteosome.

The results of the study demonstrate that E3s are quite varied in the degree to which they can degrade target proteins they are brought into contact with. The research team even discovered four of what they call ‘angry E3s,’ which consistently degrade targets regardless of other factors, such as the location of the target within the cell.

A particularly surprising finding was that some of the strongest effectors for targeted protein degradation were E2 conjugating enzymes, instead of E3s. These differ from E3s in that they are involved at an earlier step of protein degradation and do not directly engage the target protein. Because E2s were not considered to be easily druggable, they had not been harnessed for targeted protein degradation until recently. They represent, however, the untapped potential of stronger effectors than ones currently in use.

The study shows that exploring the whole proteome for induced proximity offers enormous opportunities for therapeutic interventions. KLHL40, one of the identified effectors, could potentially be hijacked for targeted protein stabilization to treat skeletal muscle disorders. The research team also found that targeted protein degradation with FBXL12 and FBXL15 effectors could be particularly useful in treating chronic myeloid leukemia.

Targeted protein degradation and stabilization are innovative methods of drug discovery that have thus far been plagued with the “protein pair problem,” where the best effector for a target protein cannot be predicted accurately. Matching a target protein with the right effector is essential to successfully, and safely, facilitate degradation and stabilization processes in tissues.

“The synthetic screening platform developed by our team solves the protein matching issue through rapid, large-scale testing of effector and target protein interactions,” said Poirson. “We’re confident that an unbiased induced-proximity approach can be used to find effectors for almost any target.”

Visiting scientist Juline Poirson

CREDIT

University of Toronto

JOURNAL

Nature

DOI

10.1038/s41586-024-07224-3 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Proteome-scale discovery of protein degradation and stabilization effectors

ARTICLE PUBLICATION DATE

22-Mar-2024

COI STATEMENT

M.T. is a co-founder of Induxion Therapeutics. The University of Toronto has filed a patent application (pending; PCT/CA2023/050511) related to proteome-scale induced proximity screens. M.T., J.P., A.D., N.A. and L.M. are listed as co-inventors. The other authors declare no competing interests.

 

Researchers invent artificial intelligence model to design new superbug-fighting antibiotics

MCMASTER UNIVERSITY

 

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MCMASTER UNIVERSITY'S JONATHAN STOKES IS ONE OF THE RESEARCHERS WHO DEVELOPED A NEW GENERATIVE AI MODEL WHICH CAN DESIGN NEW ANTIBIOTICS TO STOP THE SPREAD OF ONE OF THE WORLD’S MOST DANGEROUS ANTIBIOTIC-RESISTANT BACTERIA. 

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CREDIT: MCMASTER UNIVERSITY

 

 

 

 

 

Hamilton, ON, Mar. 22, 2024 – Researchers at McMaster University and Stanford University have invented a new generative artificial intelligence model which can design billions of new antibiotic molecules that are inexpensive and easy to build in the laboratory.  

The worldwide spread of drug-resistant bacteria has created an urgent need for new antibiotics, but even modern AI methods are limited at isolating promising chemical compounds, especially when researchers must also find ways to manufacture these new AI-guided drugs and test them in the lab.

In a new study, published today in the journal Nature Machine Intelligence, researchers report they have developed a new generative AI model called SyntheMol, which can design new antibiotics to stop the spread of Acinetobacter baumannii, which the World Health Organization has identified as one of the world’s most dangerous antibiotic-resistant bacteria. 

Notoriously difficult to eradicate, A. baumannii can cause pneumonia, meningitis and infect wounds, all of which can lead to death. Researchers say few treatment options remain. 

“Antibiotics are a unique medicine.  As soon as we begin to employ them in the clinic, we're starting a timer before the drugs become ineffective, because bacteria evolve quickly to resist them,” says Jonathan Stokes, lead author on the paper and an assistant professor in McMaster’s Department of Biomedicine & Biochemistry, who conducted the work with James Zou, an associate professor of biomedical data science at Stanford University. 

“We need a robust pipeline of antibiotics and we need to discover them quickly and inexpensively. That's where the artificial intelligence plays a crucial role,” he says.

Researchers developed the generative model to access tens of billions of promising molecules quickly and cheaply. 

They drew from a library of 132,000 molecular fragments, which fit together like Lego pieces but are all very different in nature.  They then cross-referenced these molecular fragments with a set of 13 chemical reactions, enabling them to identify 30 billion two-way combinations of fragments to design new molecules with the most promising antibacterial properties.

Each of the molecules designed by this model was in turn fed through another AI model trained to predict toxicity.  The process yielded six molecules which display potent antibacterial activity against A. baumannii and are also non-toxic. 

"Synthemol not only designs novel molecules that are promising drug candidates, but it also generates the recipe for how to make each new molecule. Generating such recipes is a new approach and a game changer because chemists do not know how to make AI-designed molecules,” says Zou, who co-authored the paper.

The research is funded in part by the Weston Family Foundation, the Canadian Institutes of Health Research, and Marnix and Mary Heersink.   

 

 

-30-

JOURNAL

Nature Machine Intelligence

DOI

10.1038/s42256-024-00809-7 

ARTICLE PUBLICATION DATE

22-Mar-2024

 

SFU Publishing Director Hannah McGregor's new book asks "Can podcasting save academia?"

SIMON FRASER UNIVERSITY

A new book from Lori Beckstead, Ian M. Cook, and SFU Publishing Director Hannah McGregor, explores how the growth of scholarly podcasting may engender radical possibilities for how we conceive of knowledge creation and peer review, and the transformative potential of new modes of creating and reviewing expert knowledge.

"Podcast Or Perish" investigates the historical development of the norms of scholarly communication and asks how podcasting might change how we think about scholarly work. Could this be the call to action academia needs?

Read on and find out!

 

Research uncovers a rare resin fossil find: A spider that aspires to be an ant

OREGON STATE UNIVERSITY

 

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MYRMARACHNE COLOMBIANA

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CREDIT: GEORGE POINAR JR.

CORVALLIS, Ore. – Arachnophobia can make humans flee at the sight of a brown recluse, black widow or even a daddy long legs, but animal predators of spiders know no such fear.

That’s why, paleobiologist George Poinar Jr. explains, some spider species have developed the defense of deception. They masquerade as a much less desirable prey – ants – and Poinar’s recent paper in Historical Biology presents an early record of an ant-mimicking spider in fossilized resin.

“Ants are particularly good creatures for spiders to pretend to be – many animals find ants distasteful or dangerous to eat,” said Poinar, who has a courtesy appointment in the Oregon State University College of Science. “Ants are aggressive in their own defense – they have a strong bite as well as a stinging venom, and they can call in dozens of nestmates as allies. Spiders, meanwhile, have no chemical defenses and are loners, which makes them vulnerable to being hunted by larger spiders, wasps and birds – predators that would rather avoid ants. So if a spider can be like an ant, it’s more likely to be unbothered.”

Spiders that disguise themselves as ants live in many locations around the globe but until now most had been able to avoid detection from fossil researchers as well as predators. The specimen that Poinar describes, which he named Myrmarachne colombiana, was entombed in a type of fossilized resin known as copal.

Copal is a less mature form of fossilized resin than amber, which is routinely dated to be 25 million or more years old. Still, copal can be up to 3 million years old.

The age of the resin in this case, however, could not be determined, said Poinar, an international expert in using plant and animal life forms preserved in amber to learn about the biology and ecology of the distant past.

The resin block he was working with, which came from Medellin, Colombia, was too small to age-test without risk of damaging the spider inside. Poinar notes there is no record of any currently living ant-mimicking spider making its home in Colombia.

“It is a challenge for spiders to accomplish this magical transformation to ants,” he said. “Ants have six legs and two long antennae, while spiders have eight legs and no antennae.”

To get around those anatomical differences, Poinar said, spiders typically position their two front legs in a way that approximates the look of antennae. But number of legs and absence/presence of antennae are not the only characteristics differentiating an ant’s appearance from a spider’s.

“The abdomen and cephalothorax of spiders are closely attached, while in ants the equivalent of these body parts are separated by a narrow segment called the petiole,” Poinar said. “And there are many other lesser structures that need to be modified in spiders for them to closely resemble ants. How is this accomplished? Most scientists say it begins with spider mutation, adaptation and then natural selection.

“However, I think there is some spider reasoning and intelligence involved too since the spiders often model their body changes after specific ants in the same environment,” he said. “In the early days, we were told that all habits of insects were the result of instincts, but that is no longer the case.”

Several groups of spiders have developed the ability to look and behave like various types of ants, he added. There are also spiders that try to blend in as other insects, such as flies, beetles and wasps.

Most of the copycat spiders belong to a few families of hunting spiders, including Salticidae or jumping spiders. The specimen in the Colombian copal appears to be a jumping spider.

Spiders that practice mimicry also come from the Corinnidae (sun spider), Thomisidae (flower spider) and Zodariidae (spotted or ant spider) families.

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JOURNAL

Historical Biology

DOI

10.1080/08912963.2024.2320190 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Myrmarachne colombiana sp. n. (Araneae: Salticidae), a new species of ant-mimic spider in copal from Colombia, South America

 

Signs of life detectable in single ice grain emitted from extraterrestrial moons

UNIVERSITY OF WASHINGTON

 

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AN ARTIST’S RENDITION OF SATURN’S MOON ENCELADUS DEPICTS HYDROTHERMAL ACTIVITY ON THE SEAFLOOR AND CRACKS IN THE MOON’S ICY CRUST THAT ALLOW MATERIAL FROM THE WATERY INTERIOR TO BE EJECTED INTO SPACE. NEW RESEARCH SHOWS THAT INSTRUMENTS DESTINED FOR THE NEXT MISSIONS COULD FIND TRACES OF A SINGLE CELL IN A SINGLE ICE GRAIN CONTAINED IN A PLUME.

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CREDIT: NASA/JPL-CALTECH

The ice-encrusted oceans of some of the moons orbiting Saturn and Jupiter are leading candidates in the search for extraterrestrial life. A new lab-based study led by the University of Washington in Seattle and the Freie Universität Berlin shows that individual ice grains ejected from these planetary bodies may contain enough material for instruments headed there in the fall to detect signs of life, if such life exists.

“For the first time we have shown that even a tiny fraction of cellular material could be identified by a mass spectrometer onboard a spacecraft,” said lead author Fabian Klenner, a UW postdoctoral researcher in Earth and space sciences. “Our results give us more confidence that using upcoming instruments, we will be able to detect lifeforms similar to those on Earth, which we increasingly believe could be present on ocean-bearing moons.”

The open-access study was published March 22 in Science Advances. Other authors in the international team are from The Open University in the U.K.; NASA’s Jet Propulsion Laboratory; the University of Colorado, Boulder; and the University of Leipzig.

The Cassini mission that ended in 2017 discovered parallel cracks near the south pole of Saturn’s moon Enceladus. Emanating from these cracks are plumes containing gas and ice grains. NASA’s Europa Clipper mission, scheduled to launch in October, will carry more instruments to explore in even more detail an icy moon of Jupiter, Europa.

To prepare for that mission, researchers are studying what this new generation of instruments might find. It is technically prohibitive to directly simulate grains of ice flying through space at 4 to 6 kilometers per second to hit an observational instrument, as the actual collision speed will be. Instead, the authors used an experimental setup that sends a thin beam of liquid water into a vacuum, where it disintegrates into droplets. They then used a laser beam to excite the droplets and mass spectral analysis to mimic what instruments on the space probe will detect.

Newly published results show that instruments slated to go on future missions, like the SUrface Dust Analyzer onboard Europa Clipper, can detect cellular material in one out of hundreds of thousands of ice grains.

The study focused on Sphingopyxis alaskensis, a common bacterium in waters off Alaska. While many studies use the bacterium Escherichia coli as a model organism, this single-celled organism is much smaller, lives in cold environments, and can survive with few nutrients. All these things make it a better candidate for potential life on the icy moons of Saturn or Jupiter.

“They are extremely small, so they are in theory capable of fitting into ice grains that are emitted from an ocean world like Enceladus or Europa,” Klenner said.

Results show that the instruments can detect this bacterium, or portions of it, in a single ice grain. Different molecules end up in different ice grains. The new research shows that analyzing single ice grains, where biomaterial may be concentrated, is more successful than averaging across a larger sample containing billions of individual grains.

A recent study led by the same researchers showed evidence of phosphate on Enceladus. This planetary body now appears to contain energy, water, phosphate, other salts and carbon-based organic material, making it increasingly likely to support lifeforms similar to those found on Earth. 

The authors hypothesize that if bacterial cells are encased in a lipid membrane, like those on Earth, then they would also form a skin on the ocean’s surface. On Earth, ocean scum is a key part of sea spray that contributes to the smell of the ocean. On an icy moon where the ocean is connected to the surface (e.g., through cracks in the ice shell), the vacuum of outer space would cause this subsurface ocean to boil. Gas bubbles rise through the ocean and burst at the surface, where cellular material gets incorporated into ice grains within the plume.

“We here describe a plausible scenario for how bacterial cells can, in theory, be incorporated into icy material that is formed from liquid water on Enceladus or Europa and then gets emitted into space,” Klenner said.

The SUrface Dust Analyzer onboard Europa Clipper will be higher-powered than instruments on past missions. This and future instruments also will for the first time be able to detect ions with negative charges, making them better suited to detecting fatty acids and lipids.

“For me, it is even more exciting to look for lipids, or for fatty acids, than to look for building blocks of DNA, and the reason is because fatty acids appear to be more stable,” Klenner said.

“With suitable instrumentation, such as the SUrface Dust Analyzer on NASA’s Europa Clipper space probe, it might be easier than we thought to find life, or traces of it, on icy moons,” said senior author Frank Postberg, a professor of planetary sciences at the Freie Universität Berlin. “If life is present there, of course, and cares to be enclosed in ice grains originating from an environment such as a subsurface water reservoir.”

The study was funded by the European Research Council, NASA and the German Research Foundation (DFG). Other co-authors are Janine Bönigk, Maryse Napoleoni, Jon Hillier and Nozair Khawaja at the Freie Universität Berlin; Karen Olsson-Francis at The Open University in the U.K.; Morgan Cable and Michael Malaska at the NASA Jet Propulsion Laboratory; Sascha Kempf at the University of Colorado, Boulder; and Bernd Abel at the University of Leipzig.

This image shows red streaks across the surface of Europa, the smallest of Jupiter’s four large moons. The upcoming Europa Clipper mission will send instruments to investigate this moon. New research shows that one of these instruments destined for the next mission could find traces of a single cell in a single ice grain ejected from the planetary body’s interior.

NASA

The drawing on the left depicts Enceladus and its ice-covered ocean, with cracks near the south pole that are believed to penetrate through the icy crust. The middle panel shows where authors believe life could thrive: at the top of the water, in a proposed thin layer (shown yellow) like on Earth’s oceans. The right panel shows that as gas bubbles rise and pop, bacterial cells could get lofted into space with droplets that then become the ice grains that were detected by Cassini.

ESA

Enceladus Bubbles (IMAGE)

UNIVERSITY OF WASHINGTON

The left panel shows the kilometers-thick icy crust believed to encapsulate Saturn’s moon Enceladus. Filling the crack is salty water with a proposed thin layer (shown orange) at its surface. The right panel shows that as gas bubbles rise and pop, they combine with organic material and get lofted into the spray.

CREDIT

Postberg et al. (2018)/Nature

JOURNAL

Science Advances

DOI

10.1126/sciadv.adl0849 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

How to identify cell material in a single ice grain emitted from Enceladus or Europa

ARTICLE PUBLICATION DATE

22-Mar-2024

 

Tudor era horse cemetery in Westminster revealed as likely resting place for elite imported animals

Isotopic biographies reveal horse rearing and trading networks in medieval London

UNIVERSITY OF EXETER

 

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EXETER RESEARCHERS ANALYSING BONES RECOVERED FROM THE HORSE CEMETERY.

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CREDIT: UNIVERSITY OF EXETER

Archaeological analysis of a near unique animal cemetery discovered in London nearly 30 years ago has revealed the international scale of horse trading by the elites of late medieval and Tudor England.

Using advanced archaeological science techniques, including studying chemical composition, researchers have been able to identify the likely origins of several physically elite horses and the routes they took to reach British shores during the formative years of their life.

These animals – akin to modern supercars – were sourced from a variety of locations across Europe specifically for their height and strength and imported for use in jousting tournaments and as status symbols of 14th- to 16th-century life. They include three of the tallest animals known from late medieval England, standing up to 1.6 metres or 15.3 hands high, which while quite small by modern standards would have been very impressive for their day.

The skeletons of the horses were recovered from a site under the modern-day Elverton Street in the City of Westminster, which was excavated in advance of building works in the 1990s. In medieval times, the cemetery would have been located outside the walled City of London but was close to the royal palace complex at Westminster.

The research, led by the University of Exeter, and funded by the Arts and Humanities Research Council, is published in the latest edition of Science Advances.

“The chemical signatures we measured in the horse’s teeth are highly distinctive and very different to anything we would expect to see in a horse that grew up in the UK,” said Dr Alex Pryor, Senior Lecturer in Archaeology and lead researcher. “These results provide direct and unprecedented evidence for a variety of horse movement and trading practices in the Middle Ages. Representatives for the King and other medieval London elites were scouring horse trading markets across Europe seeking out the best quality horses they could find and bringing them to London. It’s quite possible that the horses were ridden in the jousting contests we know were held in Westminster, close to where the horses were buried.”

In the first experiment of its kind to be conducted on medieval horse remains, the researchers took 22 molar teeth from 15 individual animals and drilled out portions of the enamel for isotope analysis. By measuring isotope ratios of the elements strontium, oxygen and carbon present within the teeth and comparing the results with known ranges in different geographies, the team was able to identify the potential origin of each horse – and accurately rule out others, including prime European horse-breeding centres such as Spain and southern Italy. 

Dr Pryor said that at least half of the horses had diverse international origins, possibly Scandinavia, the Alps and other northern and eastern European locations. The results, the researchers conclude, were consistent with the breeding patterns of royal stud farms, where horses would reside until their second or third year, before they would either be broken and trained or sent elsewhere to be sold.

Physical analysis of the teeth revealed wear suggestive of heavy use of a curb bit, often employed with elite animals, especially those groomed for war and tournaments after the 14th century. Bit wear on two of the mares also suggested they were used under saddle or in harness and for breeding. And analysis of the skeletons revealed many of them to be well above average size, with several instances of fused lower thoracic and lumbar vertebrae indicative of a life of riding and hard work.

“The finest medieval horses were like modern supercars – inordinately expensive and finely tuned vehicles that proclaimed their owner’s status,” added Professor Oliver Creighton, a medieval specialist at the University of Exeter and part of the research team. “And at Elverton Street, our research team seem to have found evidence for horses used in jousting – the sport of kings, in which riders showcased their fighting skills and horsemanship on elite mounts.

“The new findings provide a tangible archaeological signature of this trade, emphasising its international scale. It is apparent that the medieval London elite were explicitly targeting the highest quality horses they could find at a European scale.”

The paper, Isotopic biographies reveal horse rearing and trading networks in medieval London, can be accessed via Science Advances.

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JOURNAL

Science Advances

DOI

10.1126/sciadv.adj5782 

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Isotopic biographies reveal horse rearing and trading networks in medieval London

ARTICLE PUBLICATION DATE

22-Mar-2024

 

Scientists explore complex pattern of tipping points in the Atlantic’s current system

New mathematical modelling of the Atlantic meridional overturning circulation – a system of ocean currents – shows greater complexity than previously thought

UNIVERSITY OF LEICESTER

 

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PROFESSOR VALERIO LUCARINI FROM THE UNIVERSITY OF LEICESTER SCHOOL OF MATHEMATICAL AND COMPUTER SCIENCE 

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CREDIT: UNIVERSITY OF LEICESTER

An international team of scientists have warned against relying on nature providing straightforward ‘early warning’ indicators of a climate disaster, as new mathematical modelling shows new fascinating aspects of the complexity of the dynamics of climate.

It suggests that the climate system could be more unpredictable than previously thought.

By modelling the Atlantic meridional overturning circulation, one of the main ocean current systems, the team which included mathematicians from the University of Leicester have found that the stability of the system is much more complex than simple ‘on-off’ states as previously assumed. Switches between these states might lead to major changes in the regional climate of the North Atlantic region, yet a far cry from the massive impacts of a transition between the qualitatively different states.

But some of these minor transitions might eventually upscale to cause a major changeover between the qualitatively different states, with massive global climatic impacts. Early warning signals might be unable to distinguish the degree of severity of the ensuing tipping points. Like a tower of Jenga blocks, removing some blocks may affect the stability of the system, but we cannot be certain which block will bring the whole system tumbling down.        

Their findings are published in Science Advances today (22 March) in a paper led by the Niels Bohr Institute at the University of Copenhagen.

The Atlantic meridional overturning circulation is one of the most important fundamental features of the climate system. It transports heat from low to high latitudes in the northern Atlantic, so it helps create positive thermal anomalies in northern and western Europe and in the North Atlantic region downwind. A slowdown of the circulation would result in a relative cooling in this region.

Predicting the behaviour of our climate, as in the Atlantic meridional overturning circulation, is challenging due to its incredible complexity. Scientists either need a model of the highest possible resolution, or try to understand its behaviour using a less resource intensive model that allows for rigorous statistical analysis.

Professor Valerio Lucarini from the University of Leicester School of Mathematical and Computer Science said: “Within each state there is a multiplicity of nearby states. Depending on where or what you are observing, you might find some indicators of nearing collapse. But it is not obvious whether this collapse will be contained to nearby states or lead to a major upheaval, because the indicators only reflect the local properties of the system.

“These states are the different ways that the Atlantic meridional overturning circulation organises itself at large scales, with key implications for the global climate and especially regionally in the North Atlantic. Under some scenarios, the circulation could reach a ‘tipping point’ where the system is no longer stable and will collapse. Early warning indicators tell us that the system might be jumping to another state, but we do not know how different it will be.

“In a separate investigation we have seen something similar occurring in paleoclimatic records: when you change your timescale of interest – just like a magnification lens - you can discover smaller and smaller scale distinct features that are indicative of competing modes of operation of the global climate. Paleoclimatic records of the last 65 million years allowed us to provide a new interpretation of the climate evolution over that time period, and reveal these multiple competing states.

“This study paves the way to looking at the climate through the lens of statistical mechanics and complexity theory. It really stimulates a new outlook of climate, in which you have to put together complex numerical simulations, observational evidence and theory in an unavoidable mixture. You have to appreciate and endorse this complexity. There is no shortcut, no free lunch in our understanding of climate, but we are learning a lot from it.”

• ‘Multistability and Intermediate Tipping of the Atlantic Ocean Circulation’ is published in Science Advances by Johannes Lohmann (Niels Bohr Institute, University of Copenhagen, Denmark), Henk A. Dijkstra (Utrecht University, Utrecht, the Netherlands), Markus Jochum (Niels Bohr Institute, University of Copenhagen, Denmark), Valerio Lucarini (University of Leicester) and Peter D. Ditlevsen (Niels Bohr Institute, University of Copenhagen, Denmark). More information, including a copy of the paper, can be found online at the Science Advances press package at https://www.eurekalert.org/press/vancepak/
• Further background: ‘A punctuated equilibrium analysis of the climate evolution of cenozoic exhibits a hierarchy of abrupt transitions’ in Scientific Reports, DOI: 10.1038/s41598-023-38454-6, Link: https://doi.org/10.1038/s41598-023-38454-6
• The project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 820970 for the project TiPES, and from Danmarks Frie Forskningsfond under grant No. 2032-00346B, and by the European Research Council through the ERC-AdG project TAOC (project 101055096).

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JOURNAL

Science Advances

ARTICLE TITLE

Multistability and Intermediate Tipping of the Atlantic Ocean Circulation

ARTICLE PUBLICATION DATE

22-Mar-2024