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Tuesday, January 20, 2026

 

Golden Gate method enables rapid, fully-synthetic engineering of therapeutically relevant bacteriophages



Simplified bacteriophage design and synthesis to propel long-obstructed bacteriophage research in new PNAS study from New England Biolabs® and Yale University



New England Biolabs





Bacteriophages have been used therapeutically to treat infectious bacterial diseases for over a century. As antibiotic-resistant infections increasingly threaten public health, interest in bacteriophages as therapeutics has seen a resurgence. However, the field remains largely limited to naturally occurring strains, as laborious strain engineering techniques have limited the pace of discovery and the creation of tailored therapeutic strains.

Now, researchers from New England Biolabs (NEB®) and Yale University describe the first fully synthetic bacteriophage engineering system for Pseudomonas aeruginosa, an antibiotic-resistant bacterium of global concern, in a new PNAS study. The system is enabled by NEB’s High-Complexity Golden Gate Assembly (HC-GGA) platform. In this method, researchers engineer bacteriophages synthetically using sequence data rather than bacteriophage isolates. The team assembled a P. aeruginosa phage from 28 synthetic fragments, and programmed it with new behaviors through point mutations, DNA insertions and deletions. These modifications included swapping tail fiber genes to alter the bacterial host range and inserting fluorescent reporters to visualize infection in real time.

“Even in the best of cases, bacteriophage engineering has been extremely labor-intensive. Researchers spent entire careers developing processes to engineer specific model bacteriophages in host bacteria,” reflects Andy Sikkema, the paper’s co-first author and Research Scientist at NEB. “This synthetic method offers technological leaps in simplicity, safety and speed, paving the way for biological discoveries and therapeutic development.”

A new approach to bacteriophage engineering

With NEB’s Golden Gate Assembly platform, scientists can build an entire phage genome based on digital sequence data outside the cell, piece by piece, with any intended edits already included. The genome is assembled directly from synthetic DNA and introduced into a safe laboratory strain. 

The method removes long-standing challenges of relying on the propagation of physical phage isolates and specialized strains of host bacteria, a heightened challenge for therapeutically-relevant phages, which specifically infect human pathogens. In addition, the process removes the need for labor‑intensive screening or iterative editing required by in-cell engineering methods.

Unlike DNA assembly methods that join fewer and longer DNA fragments, Golden Gate Assembly’s segments are shorter, making them less toxic to host cells, easier to prepare, and much less likely to contain errors. The method is also less sensitive to the repeats and extreme GC content found in many phage genomes. 

Through simplification and increased versatility, the Golden Gate method of bacteriophage engineering dramatically shifts the window of possibilities for researchers dedicated to developing bacteriophages as therapeutic agents to overcome antibiotic resistance.

Molecular tools finding their purpose

Realizing the rapid method of synthetic bacteriophage engineering required an intersection of expertise between NEB’s scientists, who developed the basic tools to make Golden Gate reliable for large targets and many DNA fragments, and bacteriophage researchers at Yale University who recognized its potential, and reached out to collaborate on new, ambitious applications.

Researchers at NEB first worked to optimize the method in a model phage, Escherichia coli phage T7. Since then, partnering teams have worked with NEB scientists to expand the method to non-model bacteriophages that target highly antibiotic-resistant pathogens. 

A related study, which used the Golden Gate method to synthesize high-GC content Mycobacterium phages, was published in PNAS in November 2025 in conjunction with the Hatfull Lab at the University of Pittsburgh and Ansa Biotechnologies. Researchers from Cornell University have also worked with NEB to develop a method to synthetically engineer T7 bacteriophages as biosensors capable of detecting E. coli in drinking water, described in a December 2025 ACS study.

“My lab builds 'weird hammers' and then looks for the right nails,” said Greg Lohman, Senior Principal Investigator at NEB and co-author on the study. “In this case, the phage therapy community told us, 'That’s exactly the hammer we’ve been waiting for.’” 

About New England Biolabs

For over 50 years, New England Biolabs (NEB) has pioneered the discovery and production of innovative products tailored for molecular biology research. Our commitment to scientific discovery is evident in all that we do, including our ever-expanding product portfolio, investment in our basic and applied research program, and support of customers’ research in academia and industry, including cutting-edge technologies for use in molecular diagnostics and nucleic-acid vaccines development. Guided by our founding principles, NEB proactively invests in efforts to improve the well-being of our employees, surrounding communities, as well as the future of our planet. NEB remains a privately held company with global reach, supported by our headquarters in Ipswich, MA, USA, subsidiary offices in 10 countries, and over 60 distribution partners around the world. For more information about New England Biolabs, visit www.neb.com.

NEB® and NEW ENGLAND BIOLABS® are registered trademarks of New England Biolabs, Inc.

Tuesday, January 13, 2026

SPACE/COSMOS

Aboard the International Space Station, viruses and bacteria show atypical interplay


Bacteria-infecting viruses and their hosts accumulate distinctive mutations in near-weightlessness


PLOS

Aboard the International Space Station, viruses and bacteria show atypical interplay 

image: 

ISS - December 2000

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Credit: NASA on The Commons, Flickr (CC0, https://creativecommons.org/publicdomain/zero/1.0/)





In a new study, terrestrial bacteria-infecting viruses were still able to infect their E. coli hosts in near-weightless “microgravity” conditions aboard the International Space Station, but the dynamics of virus-bacteria interactions differed from those observed on Earth. Phil Huss of the University of Wisconsin-Madison, U.S.A., and colleagues present these findings January 13th in the open-access journal PLOS Biology.

Interactions between phages—viruses that infect bacteria—and their hosts play an integral role in microbial ecosystems. Often described as being in an evolutionary “arms race,” bacteria can evolve defenses against phages, while phages develop new ways to thwart defenses. While virus-bacteria interactions have been studied extensively on Earth, microgravity conditions alter bacterial physiology and the physics of virus-bacteria collisions, disrupting typical interactions.

However, few studies have explored the specifics of how phage-bacteria dynamics differ in microgravity. To address that gap, Huss and colleagues compared two sets of bacterial E. coli samples infected with a phage known as T7—one set incubated on Earth and the other aboard the International Space Station.

Analysis of the space-station samples showed that, after an initial delay, the T7 phage successfully infected the E. coli. However, whole-genome sequencing revealed marked differences in both bacterial and viral genetic mutations between the Earth samples versus the microgravity samples.

The space-station phages gradually accumulated specific mutations that could boost phage infectivity or their ability to bind receptors on bacterial cells. Meanwhile, the space-station E. coli accumulated mutations that could protect against phages and enhance survival success in near-weightless conditions.

The researchers then applied a high-throughput technique known as deep mutational scanning to more closely examine changes in the T7 receptor binding protein, which plays a key role in infection, revealing further significant differences between microgravity versus Earth conditions. Additional experiments on Earth linked these microgravity-associated changes in the receptor binding protein to increased activity against E. coli strains that cause urinary tract infections in humans and are normally resistant to T7.

Overall, this study highlights the potential for phage research aboard the ISS to reveal new insights into microbial adaption, with potential relevance to both space exploration and human health.

The authors add, “Space fundamentally changes how phages and bacteria interact: infection is slowed, and both organisms evolve along a different trajectory than they do on Earth. By studying those space-driven adaptations, we identified new biological insights that allowed us to engineer phages with far superior activity against drug-resistant pathogens back on Earth.”

 

In your coverage, please use this URL to provide access to the freely available paper in PLOS Biologyhttps://plos.io/4q4S9AO

Citation: Huss P, Chitboonthavisuk C, Meger A, Nishikawa K, Oates RP, Mills H, et al. (2026) Microgravity reshapes bacteriophage–host coevolution aboard the International Space Station. PLoS Biol 24(1): e3003568. https://doi.org/10.1371/journal.pbio.3003568

Author countries: United StatesFunding: This work was supported by the Defense Threat Reduction Agency (https://www.dtra.mil/) (Grant HDTRA1-16-1-0049) to S.R. C.C. was supported by a graduate training scholarship from the Anandamahidol Foundation (Thailand). The sponsors or funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The path to solar weather forecasts



Space-based measurements of solar eruptions are the first of their kind




University of Tokyo

Three heads are better than one 

image: 

Diagram to show the different satellites that made up the ad-hoc sensor network in this study. Their combined data helped paint a picture of how a CME in 2022 changed as it passed by the Earth on its way out of the solar system. ©2025 Kinoshita et al. CC-BY-ND

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Credit: ©2025 Kinoshita et al. CC-BY-ND





At times the sun ejects energetic material into space which can have consequences for space-based and even ground-based electronic technology. Researchers aim to understand this phenomenon and find ways to forecast it, including how ejected material evolves as it travels through the solar system. For the first time, researchers, including those from the University of Tokyo, made high-quality measurements of an evolving cloud of solar ejecta by using multiple space-based instruments which were not designed to do so, and observed the way the clouds reduce background cosmic-ray activity.

Solar storms, known as coronal mass ejections (CME), are surprisingly common. When detected in the vicinity of Earth, some satellites are even put into a safe, low-power mode until the storm passes in order to protect them. But as with more familiar terrestrial weather, it’s the events you can’t prepare for that necessarily cause the most damage. To aid in this regard, researchers are trying to figure out how CMEs evolve as they head away from their source, the sun. While some different approaches have been tried over time, a new method which pools the resources of several scientific satellites could lead to better space-weather forecasting.

“Understanding how huge clouds of solar material travel through space is essential for protecting satellites, astronauts, and even power grids on Earth,” said Ph.D. researcher Gaku Kinoshita from the Department of Earth and Planetary Science. “In our new paper, we show that the paths of these solar eruptions can be tracked using drops in cosmic rays, high-energy particles that constantly bombard the solar system, measured by spacecraft. By combining observations from several spacecraft at different locations, we were able to watch how one eruption changed shape and strength as it moved away from the sun, revealing new ways to improve space-weather forecasting.”

The researchers’ method works thanks to an effect known as Forbush decrease, which is the way a CME isn't perfectly transparent to cosmic rays coming from behind it. This is because the CME produces a strong magnetic field which can deflect charged particles like cosmic rays. By observing cosmic rays as a CME passes through a region, the team could interpret the physical makeup of the CME, and crucially, how it changes with time.

“In March 2022, three spacecraft — the European Space Agency (ESA)’s Solar Orbiter, ESA and Japan Aerospace Exploration Agency (JAXA)’s BepiColombo, and NASA’s Near Earth Spacecraft — happened to be ideally positioned to observe the same solar eruption from different locations in space. This rare alignment allowed us to compare how the event looked along different directions and distances from the sun,” said Kinoshita. “By combining cosmic-ray data with magnetic-field and solar-wind measurements, we could link changes in the particle signal directly to the physical structure of the eruption. One of the most important results of this work is showing that instruments never designed for science can still deliver valuable scientific data. We used a simple system-monitoring instrument onboard the BepiColombo spacecraft, originally meant only to keep the spacecraft healthy, and, through careful calibration, turned it into a detector of cosmic-ray decreases. Data that had long been ignored turned out to be too valuable to waste.”

While there are advanced instruments capable of monitoring CMEs directly, their operational periods are limited; whereas the above approach repurposes more general instruments that are always on, meaning they can continuously gather data. Researchers can also improve the quality of their data by combining data from multiple spacecraft — this is also important to build a 3D picture of the CMEs.

“Because the instruments used were never intended for scientific research, there was no existing framework to rely on. We had to evaluate an instrument’s behavior, calibrate it from scratch and develop new analysis methods ourselves before we could confidently use the data to study cosmic-ray decreases,” said Kinoshita. “With many spacecraft now operating between the sun and Earth, and more planned for the future, the chances of making routine multipoint observations are increasing. If we continue to combine data from multiple missions and use all available instruments, we can gain a far more complete picture of how solar ejections propagate through space.”

###

Journal: Gaku Kinoshita, Beatriz Sanchez-Cano, Yoshizumi Miyoshi, Laura Rodríguez-García, Emilia Kilpua, Benoit Lavraud, Mathias Rojo, Marco Pinto, Yuki Harada, Go Murakami, Yoshifumi Saito, Shoichiro Yokota, Daniel Heyner, David Fischer, Nicolas Andre, and Kazuo Yoshioka, “Spatiotemporal Evolution of the 2022 March Interplanetary Coronal Mass Ejection Revealed by Multipoint Observations of Forbush Decreases”, The Astrophysical Journalhttps://doi.org/10.3847/1538-4357/ae1834


Funding: This work was supported by JST SPRING (JPMJSP2108), STFC (ST/V004115/1 and ST/Y000439/1), the European Space Agency, the German Ministry for Economic Affairs and Climate Action / DLR (50QW2202), CNES, and the Institute for Space-Earth Environmental Research (ISEE), Nagoya University.

 

Useful links:

Graduate School of Frontier Sciences

https://www.k.u-tokyo.ac.jp/en/

 

Department of Complexity Science and Engineering

https://www.k.u-tokyo.ac.jp/complex/index_e.html

 

Graduate School of Science

https://www.s.u-tokyo.ac.jp/en/
 

Department of Earth and Planetary Science

https://www.eps.s.u-tokyo.ac.jp/en/


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