Tuesday, May 19, 2026

Protein engineering and testing condensed to a single day

Stanford University

Proteins are critical to life – and to industry. There are countless proteins that could be engineered to treat and even cure serious diseases and cellular dysfunctions. Industrial applications are similarly promising, with proteins increasingly used as enzymes in food manufacturing and in consumer detergents.

While AI can help suggest improvements, each novel protein must still be created in the real world and tested for performance. It is a labor-intensive process that involves constructing the DNA instructions for each protein in yeast or bacteria and growing individual clones for protein production and testing. This can take many days for a single protein of interest and even longer if the protein needs to be tested in mammalian cells, a process that requires retrieving DNA from microbes for transfer to the mammalian cells.

In a new paper, Michael Z. Lin, a professor of neurobiology and of bioengineering in the schools of Engineering and Medicine, and graduate students, Yan Wu in bioengineering and Pengli Wang* in chemical engineering, say they have condensed the time-intensive protein building and testing process to just 24 hours. They call their approach MIDAS for Microbe-Independent Deep Assembly and Screening. MIDAS could rapidly accelerate biological research in fields stretching from oncology to environmental sciences. The study introducing MIDAS appears in the journal Molecular Systems Biology.

“The fundamental questions of molecular biology remain: how do we make better proteins and how do we understand what makes a protein work?” Lin says. “Doing that work takes valuable time and resources, but we’ve found a way to dramatically reduce those demands.”

Going in circles

Lin and colleagues leapfrogged the traditional microbial assembly process by using a genetic replication technique known as polymerase chain reaction (PCR). PCR can amplify linear segments of DNA into millions or billions of copies very quickly. By using PCR to build entire genes used by mammalian cells to express a given protein, they bypassed the need for microbial cloning and DNA transfer. The PCR-produced gene variations can be directly transferred into mammalian cells for functional analysis. The only requirement for the PCR procedure is short strings of DNA known as “primers” that can be ordered for next-day delivery.

“With MIDAS, we can receive PCR primers in the morning, assemble the necessary genes by mid-day, and by late afternoon transfer the genes into cells to observe how the proteins function,” says co-first author Yan Wu. “And we can do this all for hundreds or thousands of protein variants in parallel at a time.”

In traditional protein engineering, when researchers identify a promising variant, they have to assemble and clone the gene expressing the protein into a circular genetic structure known as a plasmid. They must then transfer the modified plasmids into the DNA of bacteria or yeast to produce suitable quantities of each unique plasmid DNA, which must then be transferred into mammalian cells for validation.

This clone-and-transfer process is laborious, slow, and expensive, and it greatly restricts the number of variants that can feasibly be evaluated. MIDAS changes that calculus. Lin and team’s key insight was to do away with the circular plasmids, which are incompatible with PCR. Instead, they treat DNA as linear information that is ideally suited to PCR. This allows them to assemble hundreds of gene variants at a time and directly transfer them into mammalian cells in quantity to identify the best performers quickly and cost-effectively.

With MIDAS, we can receive PCR primers in the morning, assemble the necessary genes by mid-day, and by late afternoon transfer the genes into cells.
Yan Wu

“We decided there’s nothing magical about the circular structure of plasmids,” Lin says. “For PCR, you just need the genetic data. That was the moment of inspiration.”

A practical test of 384 variants using MIDAS took about four hours of hands-on lab work and about $2,000 in reagents. By existing methods, an experienced researcher would need approximately 192 hours and about $20,000 in reagents to evaluate just 24 variants. The researchers calculate that MIDAS is almost 50-times faster and a tenth the cost of cloning-based approaches.

Immediate impact

MIDAS could have immediate real-world implications for biological research. First, it should accelerate important enzyme and biosensor studies, the researchers say. Second, it could improve the automatic production of PCR primers that are ideally suited to modern liquid-handling robots, which can evaluate hundreds of new proteins at a time. Last, and perhaps most importantly, they believe MIDAS could drive better and bigger sequence-fitness datasets that could improve data-intensive AI training, leading to ever more powerful molecular design models.

“We used MIDAS not only to find the best-performing version of a protein but also to understand how well closely related variants work, which is information we can use to train AI models,” says co-first author Pengli Wang. “MIDAS is so easy that we can use it to create large data sets very quickly.”

Looking forward, Lin believes MIDAS could yield deeper combinatorial searches, tighter integration with robotics, and the generation of gene sequence-molecular fitness maps to feed improved machine-learning models that can fuel computational design and experimental validation.

“MIDAS is at least an order-of-magnitude faster at real-world validation,” Lin says. “It compresses the engineering design-build-test cycle for proteins to just a couple of days, and we think it could drive rapid advances in AI-inspired molecular biology.”

For more information

Contributing authors include Lan Xiang Liu and Daesun Song of Stanford University; and authors from Fudan University, Shanghai, China; and the Promega Corporation. Lin is also a member of Stanford Bio-X, the Cardiovascular Institute, the Maternal & Child Health Research Institute, the Stanford Cancer Institute, and the Wu Tsai Neurosciences Institute, and a faculty fellow of Sarafan ChEM-H.

Funding for MIDAS was provided by NIH, a Stanford Bio-X Interdisciplinary Initiatives Program Seed Grant, a Stanford Bio-X PhD Fellowship, and a Stanford Wu Tsai Neurosciences Institute Interdisciplinary Graduate Fellowship.

*Pengli Wang passed away in May 2026 after this research was completed. He was a fourth-year PhD student in chemical engineering.

Journal

Molecular Systems Biology

DOI

10.1038/s44320-026-00210-z

Article Title

Fast analysis and engineering of protein function by microbe-independent deep assembly and screening

What we now know about how smoking stiffens lungs

Experimental testing on human lungs could improve ventilators

University of California - Riverside

Digital lung modeled on real lung experiment — video:
Video shows a digital model being created from breathing experiments on a lung from a donor.
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Credit: Mona Eskandari/UCR

For the first time, scientists have directly measured how smoking changes the mechanical behavior of human lung tissue.

Published in the Journal of the Royal Society Interface, the study directed by UC Riverside mechanical engineer Mona Eskandari, examines human lung parenchyma, which is the soft, spongy tissue that makes up the bulk of the lung organ. The researchers found that smoking substantially stiffens this tissue in ways resembling fibrosis, a disease that scars and toughens the lungs.

Using human lungs from donors that were either transplant-eligible or designated for research use, the researchers removed small square samples of the parenchyma, then mechanically stretched the tissue while measuring how much force it resisted.

The differences between smokers and nonsmokers were striking. Tissue from smokers became significantly stiffer as it stretched, resisting expansion more strongly than healthy tissue. This is similar to the way scar-like tissue makes breathing progressively more difficult in people suffering from fibrosis.

Though lungs expand in many directions simultaneously with each breath, previous studies stretched tissue in only one direction or relied entirely on animal models. Eskandari’s lab instead conducted tensile tests by extending tissue across multiple axes at once to better mimic the mechanics of real breathing.

The study also revealed that lungs are mechanically nonuniform. Tissue sampled from upper lung regions was generally stiffer than tissue from lower regions, even within the same lobe.

Researchers believe gravity may potentially explain the difference. Because humans stand upright, the upper lungs experience different long-term forces than the lower lungs.

Those uneven mechanics could have important medical consequences. The findings may help explain why certain forms of lung damage, including ventilator-induced lung injury, do not spread evenly throughout the organ. Some regions may be more vulnerable to overstretching than others.

The researchers also measured how much energy lung tissue loses during repeated stretching cycles. Human lung tissue dissipated more energy than researchers typically observe in mice, a finding that may help explain why animal studies do not always accurately represent human lung behavior.

That distinction is increasingly important because scientists are building sophisticated computational “digital twin” lungs designed to simulate breathing, disease progression, and medical interventions. If those models are based only on animal data, Eskandari said, they may fail to capture critical aspects of human lung mechanics and make it harder to use the findings in clinical settings.

The researchers also observed preliminary trends suggesting lungs stiffen with age, though Eskandari cautioned that additional donor samples are needed before drawing definite conclusions. Human donor lungs suitable for this kind of testing are rare, limiting the size of the study.

Even so, the work provides one of the most detailed mechanical datasets yet collected for human lung parenchyma. The findings could eventually improve computational lung models, ventilation strategies, and surgical planning tools designed to predict how diseased lungs respond to physical stress.

Eskandari is the founder of the biomechanics Experimental and Computational Health (bMECH) laboratory at UCR to explore questions about the mechanics of biological tissues. Her cutting-edge research was recently featured in New York Times bestselling author Mary Roach’s new book, Replaceable You: Adventures in Human Anatomy, which explores the evolution of mechanical breathing support.

“We are trying to understand the biological materials we are working with,” said Eskandari. “If we want ventilators and predictive tools that truly reflect how people breathe, these technological advances need to be informed by human-based lung data.”

UCR mechanical engineer Mona Eskandari speaking at an invited seminar; Caltech, Pasadena, CA.

Credit

Mona Eskandari/UCR

Journal

Journal of The Royal Society Interface

DOI

10.1098/rsif.2025.0721

Article Title

Human lung parenchyma: tensile mechanics and the effects of smoking

Article Publication Date

13-May-2026

Silver vine or catnip? When cats can choose, silver vine wins

Cats respond more reliably to silver vine than to catnip, despite catnip’s abundant active compounds

Iwate University, Japan

outline of research — video:
The video clip for explaining the article.
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Credit: Reiko Uenoyama

What plant do cats love most?

In Europe and North America, many people would probably answer “catnip.” In Japan, the answer would more likely be silver vine (matatabi in Japanese). Both plants are famous for triggering the well-known feline response: cats rub their faces and bodies against them, roll on the ground, and sometimes lick or chew the leaves.

Previous work by the same research group showed that these plant-derived compounds can repel mosquitoes, suggesting that the behavior may function as a form of natural pest defense. But what happens when cats encounter catnip and silver vine at the same time in a more natural, free-choice setting? Do they choose silver vine, catnip, or both?

A research team from Iwate University and Nagoya University in Japan has found that domestic cats respond more reliably to silver vine (Actinidia polygama) than to catnip (Nepeta cataria) under free-choice conditions. The finding challenges a simple assumption: that a plant containing more active chemical compounds will necessarily produce a stronger behavioral response.

In outdoor experiments in Morioka, Japan, the researchers placed fresh silver vine branches and leaves near living catnip plants in a garden that free-roaming cats could enter and leave. Over ten presentation nights, six identifiable cats were recorded visiting the site. Five of them showed rubbing and rolling behavior toward silver vine, while none showed the same behavior toward either the growing catnip plant or freshly harvested catnip material. The team then compared plant extracts. When catnip and silver vine extracts were presented in the same outdoor setting, cats again showed a stronger tendency to respond to silver vine-derived stimuli.

To test whether this pattern was limited to a small group of local free-roaming cats, the researchers next studied 22 captive purebred cats housed at two facilities in Japan. The cats represented breeds originating from Europe, the United States, and the Middle East. They were tested in a large indoor environment where they could move freely, rather than in individual cages, allowing them to approach, investigate, or ignore the stimuli on their own. When catnip and silver vine extracts were presented simultaneously, 15 cats responded only to the silver vine extract, three responded only to the catnip extract, one responded to both, and three sniffed the papers but did not rub or roll. Overall, cats were significantly more likely to respond to silver vine extract than to catnip extract.

The result was surprising because chemical analysis showed that the catnip used in the study contained abundant active compounds. In fact, the catnip extract contained substantial amounts of cis-trans nepetalactone, a major active compound known to induce the feline response. The total amount of measured bioactive compounds in catnip was about 170 times higher than that in the silver vine extract used in the study.

Further laboratory tests confirmed that these catnip compounds were indeed biologically active. When cats were tested individually in cages, catnip extract and purified nepetalactone isomers found in catnip, compounds made of the same atoms but arranged in slightly different shapes, could trigger the typical rubbing and rolling response. This means that the weak response to catnip under free-choice conditions cannot be explained simply by the absence of active chemicals.

“At first glance, this was counterintuitive,” says Professor Masao Miyazaki of Iwate University, who led the research project. “One might expect a plant containing more active compounds, and compounds that clearly work in laboratory tests, to trigger a stronger behavioral response under free-choice conditions. But that was not what we observed.”

Why cats responded less reliably to catnip remains unclear. One possibility is that fresh catnip may release too much of these active compounds. In other words, the odor may be too strong when cats encounter the living plant. If the odor is intense and continuously released, cats may detect it but be less likely to proceed to rubbing and rolling.

Interestingly, a similar observation was recorded more than 250 years ago. In The Gardeners Dictionary, published in 1768, Philip Miller wrote that cats were especially fond of catmint, now commonly known as catnip, “when it is withered,” but that they tended not to disturb it when a large quantity grew together. Although this was an anecdotal observation rather than a controlled experiment, it closely resembles the pattern suggested by the present study: the amount and presentation of catnip odor may strongly influence whether cats choose to engage with it.

This idea may also help explain why many commercial catnip products use dried leaves. During drying, some volatile nepetalactone isomers may evaporate, possibly reducing the odor to a level that is more effective for inducing the feline response.

“Catnip can make cats respond in laboratory tests, but that does not mean cats will choose it in a more natural, free-choice setting,” says first author Reiko Uenoyama, an assistant professor at Iwate University. “Our study shows that what cats can respond to and what they actually choose are not always the same.”

The findings suggest that real-world behavior depends not only on the presence of active compounds, but also on how the odor is presented and whether animals voluntarily approach and interact with it.

“This study suggests that silver vine is a particularly reliable stimulus for inducing cats’ self-anointing behavior,” says Professor Miyazaki. “It also reminds us that animal behavior should be studied in settings where animals can make their own choices.”

These insights may help improve enrichment materials for domestic cats and provide a broader framework for understanding how chemical cues influence animal behavior in real-world environments.

Journal

Journal of Chemical Ecology

DOI

10.1007/s10886-026-01717-3

Method of Research

News article

Subject of Research

Animals

Article Title

Free-Roaming and Captive Cats Prefer Silver Vine to Catnip for Self-Anointing

Article Publication Date

12-May-2026

DNA floating in seawater is now enough to let scientists monitor the health of America’s dolphin populations

Scientists shows that simply sampling seawater can reveal health of dolphin populations, in a first for conservation

Frontiers

Dolphin school — image:
Common bottlenose dolphins off Southern California, USA. Photograph by John Durban / Holly Fearnbach using a drone at 200ft, authorized by NMFS Research Permit # 22306
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Credit: John Durban / Holly Fearnbach

DNA is everywhere in the world’s oceans – not only packaged inside cells from skin, scales, mucous, feces, and blood, but also floating freely. Sequencing such ‘environmental DNA’ (eDNA) from open water has long been used as a cost-effective way of gauging the number and identity of species in a region, especially when they are rare and elusive or living at great depths.

But species richness is only the most basic biodiversity measure. Until now, eDNA-based methods could only give limited insight into the variables that are most relevant for conservation: the number of individuals, the evenness of the abundances of co-occurring species, or their within-species genetic diversity. But that may be about to change, shows a new, groundbreaking study in Frontiers in Marine Science.

“Here we show that repeated eDNA sampling can be used to estimate the genetic diversity of dolphins that occur in large schools and have very large populations,” said corresponding author Dr Frederick Archer from the NOAA/NMFS Southwest Fisheries Science Center in La Jolla, California.

“This is important because genetic diversity, its outcome measure, can be used as a measure of population size and how ready a population is to react to changes in its environment.”

Around Santa Catalina Island, located 47 km off Long Beach in California, in October and December 2021, the researchers followed 15 schools of dolphins with small boats. They focused on the most common species locally: long-beaked common dolphins, short-beaked common dolphins, common bottlenose dolphins, and Risso’s dolphins. The project was directed the Marine Mammal Institute of Oregon State University (OSU), with funding from the US Office of Naval Research (ONR).

Whenever they encountered a school, the researchers collected a series of two-liter samples of seawater from the surface within 10 meters from the animals. Back in the laboratory, they sequenced each sample’s mitochondrial eDNA in the laboratory – paying particular attention to quality control – and compared the observed genetic diversity to that in public databases.

The scientists found 836 mitochondrial sequence variants in 126 water samples, of which 76% were from cetaceans and 60% from toothed whales. Overall, 29% were from the species of the school, which had been visually identified. Long-beaked common dolphins had the greatest genetic diversity, followed by short-beaked common dolphins, while Risso's and bottlenose dolphins proved much less diverse around Santa Catalina.

“Our study demonstrates the utility [of eDNA surveys] for efficiently assessing and comparing genetic diversity in social odontocetes,” concluded the authors.

The data indicated that in general, taking as many samples as feasible from multiple schools helps to gain an accurate estimate of the genetic diversity. The researchers calculated that between 60 and 72 liters of seawater would be enough for long-beaked common dolphins, the most diverse around Santa Catalina. But they emphasized that this volume may depend on the species.

“The temperature and salinity of the water are expected to affect the rate of skin shedding. Faster swimming affects shedding as well as respiration, so that DNA will be released through air blows at different rates. Feeding rate and prey should affect the frequency and composition of their defecation. The size of schools and behavior are also likely to be important, as bodies rubbing together or aerial activity such as breaching will promote shedding,” hypothesized Archer.

The authors are eager to put their methods to good use in conservation, now that they have been proven to work.

“It would be good to start eDNA monitoring programs as soon as possible that were not possible before. For example, we will be able to see how species composition in very small areas change over the course of a year – including rarer species that we don’t often detect on visual surveys,” said Archer.

“This can give us a lot of information on habitat use and will also allow us to potentially observe how environmental changes and anthropogenic effects such as pollution or underwater sound affect species distributions.”

Journal

Frontiers in Marine Science

DOI

10.3389/fmars.2026.1756593

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Estimating genetic diversity of abundant oceanic dolphins through repeated environmental (e)DNA sampling

Article Publication Date

19-May-2026

Common bottlenose dolphins off Southern California, USA. Photograph by John Durban / Holly Fearnbach using a drone at 200ft, authorized by NMFS Research Permit # 22306

Long-beaked common dolphins off Southern California, USA. Photograph by John Durban / Holly Fearnbach using a drone at 200ft, authorized by NMFS Research Permit # 19091

Risso's dolphins off Southern California, USA. Photograph by John Durban / Holly Fearnbach using a drone at 200ft, authorized by NMFS Research Permit # 19091

Risso's dolphins off Southern California, USA. Photograph by John Durban / Holly Fearnbach using a drone at 200ft, authorized by NMFS Research Permit # 19091

Risso's dolphins off Southern California, USA. Photograph by John Durban / Holly Fearnbach using a drone at 200ft, authorized by NMFS Research Permit # 19091

Avoidable inequalities remain in cardiovascular disease burden and care

European Society of Cardiology

Key takeaways

The latest cardiovascular disease (CVD) statistics from the ESC Atlas of Cardiology have been published in the European Heart Journal.

CVD continues to be a leading health challenge − the report highlights that CVD is responsible for more than 3 million deaths and 68 million healthy years of life lost annually across ESC member countries.

Great steps forward in cardiovascular medicine are at risk of being offset by the high prevalence of risk factors such as hypertension, dyslipidaemia and obesity. · Middle-income countries continue to experience roughly double the incidence of CVD mortality of high-income nations, underscoring the need for stronger health system investment and more equitable service provision.

Sophia Antipolis, France – 19 May 2026: Cardiovascular disease (CVD) remains one of Europe’s biggest health challenges, according to new data from the European Society of Cardiology (ESC) Atlas of Cardiology, published in the European Heart Journal.1

The ESC Atlas of Cardiology celebrates its 10-year anniversary with the fifth edition of the ESC Atlas report. The publication again demonstrates that CVD is the most common cause of death in more than 50 ESC member countries studied. “The new report shows that CVD was responsible for more than 3 million deaths and 68 million healthy life-years lost annually. These are not abstract statistics − they represent lives lost too early, people living with long-term illness and health systems under growing pressure,” said Professor Adam Timmis, co-first author of the publication.

In line with previous ESC Atlas editions, a central message is the persistent and avoidable inequalities in cardiovascular risk, outcomes and access to care. Middle-income countries continue to experience roughly double the mortality of high-income nations. Professor Steffen Petersen, co-first author, noted: “Europe does not have one cardiovascular reality – ESC Atlas data show that the CVD burden is uneven across ESC countries. While there has been real progress in some countries, in many there are important gaps related to access to advanced diagnostics, procedures and specialist workforce.”

New ESC Atlas data emphasise the growing importance of wider determinants of cardiovascular health, with air pollution levels twice as high in middle-income countries as in high-income countries. In addition, the prevalence of vaping, particularly in young people, underscores the lack of evidence supporting e-cigarettes as an effective smoking cessation tool. The use of e-cigarettes increases the likelihood of later cigarette smoking among minors,2 strengthening the need for clearer regulation and youth-focused prevention policies.

The high prevalence of clinical risk factors such as hypertension, dyslipidaemia, obesity and diabetes remains a concern. Professor Timmis noted: “The progress that has been made in reducing the CVD burden across some ESC member countries is at risk of being offset by the epidemic of obesity and diabetes. The scale of the healthy life-years lost due to modifiable risk factors supports urgent efforts to improve prevention across a person’s life and aid early detection and guideline implementation. The medical and economic costs of inaction are huge.”

Female disadvantage is evident across many of the variables studied, including lower access to key cardiac procedures. While the ESC Atlas report highlighted that 40% of cardiologists are women, only 11.5% of interventional cardiologists are women, with even fewer women in cardiac surgery (8.8%).

“A major strength of the ESC Atlas is the contributions of the ESC National Cardiac Societies, which provide not only a picture of disease burden, but also a practical representation of how cardiovascular care is delivered, to whom and by whom in different countries,” explained Professor Petersen, who concluded: “The ESC Atlas is not just about describing the problem. Mapping these gaps is the first step towards closing them with targeted policy action, guiding investment and supporting national cardiovascular strategies that reduce inequalities.”

In addition to the fifth published edition, interactive data dashboards showing inequalities in CVD across more than 50 countries are freely available at eAtlas.

Previous editions of ESC Atlas data were presented to EU health ministers as part of discussions that led to the recent launch of the Safe Hearts Plan, which aims to anchor CVD at the centre of Europe’s public health agenda.

ENDS

References:

[1] Timmis A, Petersen SE, et al. European Society of Cardiology: Cardiovascular Disease Statistics 2025. Eur Heart J. 2026. https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehag345

[2] Hammond D, Reid JL, Cole AG, et al. Electronic cigarette use and smoking initiation among youth: a longitudinal cohort study. CMAJ. 2017;189:E1328−E1336.

Journal

European Heart Journal

DOI

10.1093/eurheartj/ehag345

Method of Research

Data/statistical analysis

Subject of Research

People

Article Title

European Society of Cardiology: cardiovascular disease statistics 2025

Article Publication Date

19-May-2026