Some stars have been seen releasing superflares over 10 times larger than the largest solar flare ever seen on the Sun. The hot ionized gas released by solar flares can influence the environment around the Earth, referred to as space weather. More powerful superflares must have an even greater impact on the evolution of any planets forming around the star, or the evolution of any life forming on those planets. But the details of how superflares and prominence eruptions on stars occur have been unclear.

A team led by Shun Inoue at Kyoto University used the 3.8-m Seimei Telescope in Japan and the Transiting Exoplanet Survey Satellite (TESS) to monitor the binary star system V1355 Orionis which is known to frequently release large-scale superflares. V1355 Orionis is located 400 light years away in the constellation Orion.

The team succeeded in capturing a superflare with continuous, high temporal resolution observations. Data analysis shows that the superflare originated with a phenomenon known as a prominence eruption. Calculating the velocity of the eruption requires making some assumptions about aspects that aren’t directly observably, but even the most conservative estimates far exceed the escape velocity of the star (347 km/s), indicating that the prominence eruption was capable of breaking free of the star’s gravity and developing into Coronal Mass Ejections (CMEs). The prominence eruption was also one of the most massive ever observed, carrying trillions of tons of material.

The research has significant implications in the fight against bacterial resistance by optimizing the prescription and use of currently available antibiotics and enhancing the efforts to discover new ones.

Developed by a research team of UC Santa Barbara scientists, the antibiotic study was published in the journal Cell Reports Medicine. The research addressed a fundamental flaw in the healthcare paradigm for determining antibiotic resistance. It does not account for environmental conditions in the body that impact drug potency.

By simulating conditions in the body, the new test identified several effective antibiotics rejected by standard testing. Further, when the new and standard tests agreed — a nearly perfect prediction of treatment success or failure was observed.

The study required a tour de force screening of more than 500 antibiotic-bacteria combinations. The findings suggest that the standard test is incorrect ~15% of the time. And since physicians rely on this test for treatment decisions — it may lead to prescription of the wrong antibiotic.

The project was led by professor Michael Mahan and his UC Santa Barbara research team of Douglas Heithoff, Lucien Barnes and Scott Mahan, along with Santa Barbara Cottage Hospital physicians Lynn Fitzgibbons, M.D. and Jeffrey Fried, M.D., and professor John House of University of Sydney, Australia.

“People are not Petri plates — that is why antibiotics fail,” said Mahan. “Testing under conditions that mimic the body improves the accuracy by which lab tests predict drug potency.”

Physicians are aware of the flaws in the gold-standard test. When recommended antibiotics do not work, they must rely on their experience to decide on the appropriate antibiotic(s) for their patients.

This study provides a potential solution to address the disparity between antibiotics indicated by standard testing and actual patient outcomes.

“Reevaluation of FDA-approved antibiotics may be of far greater benefit than the time and cost of developing new drugs to combat antimicrobial resistance,” explained Fitzgibbons, an infectious disease physician, “potentially leading to significant life-savings and cost-savings.”

“Sepsis treatments are expensive and require long hospital stays,” explained Heithoff, “and testing and re-testing is not only time- and labor-intensive, but also leads to antibiotic resistance.”

The new test will lead to reduced costs for the healthcare industry in their efforts to identify new drugs to fight antimicrobial resistant infections.

“More accurate testing reduces the costs of drug discovery by streamlining detection of lead candidates long before expensive human clinical trials,” said House, a clinical veterinarian.

Added Fried, a critical care physician, “Human clinical safety and efficacy studies will need to be conducted to assure these findings are applicable to patients with various infections and sepsis.”

This research was funded by grants from the National Institutes of Health’s National Heart, Lung, and Blood Institute, and the U.S. Army Research Office via the Institute for Collaborative Biotechnologies (ICB) cooperative agreement and contract.

“As a Gaucho, I’m always proud to advance legislation that delivers critical support for the great work that UCSB ICB and other researchers are doing,” said Rep. Salud Carbajal. “With the support provided from the laws created by my colleagues and I on the Armed Services Committee, UCSB ICB was able to develop a new test method which revealed that FDA-approved antibiotics can effectively treat multidrug-resistant superbugs. This would be a game changer for many in our community with limited access to health care, and I’m proud to see the support included in the legislation I helped get signed into law play a part in this breakthrough.”

Rice University bioengineer Omid Veiseh and collaborators identified new biomaterial formulations that could help turn the page on Type 1 diabetes treatment, opening the door to a more sustainable, long-term, self-regulating way to handle the disease.

To do so, they developed a new screening technique that involves tagging each biomaterial formulation in a library of hundreds with a unique “barcode” before implanting them in live subjects.

According to the study in Nature Biomedical Engineering, using one of the alginate formulations to encapsulate human insulin-secreting islet cells provided long-term blood sugar level control in diabetic mice. Catheters coated with two other high-performing materials did not clog up.

“This work was motivated by a major unmet need,” said Veiseh, a Rice assistant professor of bioengineering and Cancer Prevention and Research Institute of Texas scholar. “In Type 1 diabetes patients, the body’s immune system attacks the insulin-producing cells of the pancreas. As those cells are killed off, the patient loses the ability to regulate their blood glucose.”

For decades, scientists labored toward what Veiseh called a “‘holy grail’ goal of housing islet cells inside a porous matrix made out of a protective material that would allow the cells to access oxygen and nutrients without getting clobbered by the host’s immune system.”

However, materials with optimal biocompatibility proved very hard to find, due in part to screening constraints. On one hand, immune system response to a given implanted biomaterial can only be assessed in a live host.

“The problem is the immune response needs to be investigated inside the body of these diabetic mice, not in a test tube,” said Boram Kim, a graduate student in the Veiseh lab and co-lead author on the study. “That means that if you want to screen these hundreds of alginate molecules, then you need to have hundreds of animal test subjects. Our idea was to screen for hundreds of biomaterials at the same time, in the same test subject.”

On the other hand, different biomaterial formulations look the same, making it impossible to identify high-performing ones in the absence of some telltale trait. This made testing more than one biomaterial per host unfeasible.

“They are different materials but they look the same,” Veiseh said. “And once they are implanted in the body of a test subject and then taken out again, we cannot distinguish between the materials and we would be unable to identify which material formulation worked best.”

To overcome these constraints, Veiseh and collaborators came up with a way to tag each alginate formulation with a unique ‘barcode’ that allowed them to identify the ones that performed best.

“We paired each modified biomaterial with human umbilical vein endothelial cells (HUVEC) from a different donor,” Kim said.

“The HUVEC cells, because they come from unique donors, act as a barcode that allows us to tell what material was used initially,” Veiseh added. “The winners are the ones that have live cells in them. Once we found them, we sequenced the genome of those cells and figured out which material was paired with it. That’s how we uncovered the greatest hits.”

Trials are underway for stem cell-derived islet cell use in diabetic patients. However, current islet treatments require immunosuppression, making it a taxing way to treat Type 1 diabetes.

“Currently, in order to use implanted islet cells in diabetic patients, you have to suppress the entire immune system, just as if you were trying to do an organ transplant,” Veiseh said. “That comes with a lot of complications for the patient.

“They can develop cancer, they can’t fight infections, so, for the vast majority of patients, it’s better to actually do the insulin therapy where they inject themselves. With this biomaterial-encapsulation strategy, no immunosuppression is needed.”

Placing actual HUVEC cells inside the biomaterial capsules increased the likelihood that the host immune system would detect a foreign presence. This makes the experiment more robust than simply testing for immune response to the biomaterials alone.

“We wanted to test a library of these materials, with the selection pressure of having cells inside the beads that makes it harder for the material to not get noticed by the immune system,” Veiseh said. “There’s a lot of interest from all the islet cell manufacturers to be able to get rid of immunosuppression and instead use these alginate hydrogel matrices to protect the implanted cells.”

The new high-throughput “barcoding” approach can be deployed to screen for other medical applications using fewer live test subjects.

“That actually feeds into a lot of other projects in my lab where we’re doing biologic production from cells for other disease indications,” Veiseh said. “The same modifications can be applied to all types of materials that go into the body. This is not limited only to cell transplantation. The technology we developed can be paired with a lot of different device concepts.

“For instance, some diabetic patients use automated pump systems to self-administer insulin. The catheters on those pump systems have to be replaced every few days because they get clogged. We were able to show that coating the catheters with these new materials prevented clogging.”

“With this new cell-based barcoding technology, biomaterials research just got an unprecedented boost that will accelerate the translation to clinically applicable products, and make it more affordable,” said Dr. José Oberholzer, a transplant surgeon and bioengineer at the University of Virginia.

“This is a real paradigm shift. With this method, we can now screen hundreds of biomaterials at once and select those that the human body does not reject. We can protect cellular grafts from the assaults of the immune system, without the need for immunosuppressive medications,” Oberholzer added.

Former Rice bioengineering professor and current NuProbe U.S. CEO David Zhang noted that “high-throughput DNA sequencing has revolutionized many biomedical fields.”

“I am pleased to work with Omid to enable the development of improved biomaterials using my team’s expertise in DNA sequencing,” added Zhang, who was a co-investigator on the grant. “These improved biomaterials can enable durable implanted cell therapies to function as living drug factories, and can have a positively disruptive impact on patients with a variety of chronic diseases.”

The National Institutes of Health (R01 DK120459), JDRF (3-SRA-2021-1023-S-B), the National Science Foundation (CBET1626418), the Rice University Academy Fellowship and Rice’s Shared Equipment Authority supported the research.

As described April 28, 2023 in Science, they have now extended this research using synthetic biology to engineer a solution that keeps cells from reaching their normal levels of deterioration associated with aging. Cells, including those of yeast, plants, animals and humans, all contain gene regulatory circuits that are responsible for many physiological functions, including aging.

“These gene circuits can operate like our home electric circuits that control devices like appliances and automobiles,” said Professor Nan Hao of the School of Biological Sciences’ Department of Molecular Biology, the senior author of the study and co-director of UC San Diego’s Synthetic Biology Institute.

However, the UC San Diego group uncovered that, under the control of a central gene regulatory circuit, cells don’t necessarily age the same way. Imagine a car that ages either as the engine deteriorates or as the transmission wears out, but not both at the same time. The UC San Diego team envisioned a “smart aging process” that extends cellular longevity by cycling deterioration from one aging mechanism to another.

In the new study, the researchers genetically rewired the circuit that controls cell aging. From its normal role functioning like a toggle switch, they engineered a negative feedback loop to stall the aging process. The rewired circuit operates as a clock-like device, called a gene oscillator, that drives the cell to periodically switch between two detrimental “aged” states, avoiding prolonged commitment to either, and thereby slowing the cell’s degeneration.

These advances resulted in a dramatically extended cellular lifespan, setting a new record for life extension through genetic and chemical interventions.

As electrical engineers often do, the researchers in this study first used computer simulations of how the core aging circuit operates. This helped them design and test ideas before building or modifying the circuit in the cell. This approach has advantages in saving time and resources to identify effective pro-longevity strategies, compared to more traditional genetic strategies.

“This is the first time computationally guided synthetic biology and engineering principles were used to rationally redesign gene circuits and reprogram the aging process to effectively promote longevity,” said Hao.

Several years ago the multidisciplinary UC San Diego research team began studying the mechanisms behind cell aging, a complex biological process that underlies human longevity and many diseases. They discovered that cells follow a cascade of molecular changes through their entire lifespan until they eventually degenerate and die. But they noticed that cells of the same genetic material and within the same environment can travel along distinct aging routes. About half of the cells age through a gradual decline in the stability of DNA, where genetic information is stored. The other half ages along a path tied to the decline of mitochondria, the energy production units of cells.

The new synthetic biology achievement has the potential to reconfigure scientific approaches to age delay. Distinct from numerous chemical and genetic attempts to force cells into artificial states of “youth,” the new research provides evidence that slowing the ticks of the aging clock is possible by actively preventing cells from committing to a pre-destined path of decline and death, and the clock-like gene oscillators could be a universal system to achieve that.

“Our results establish a connection between gene network architecture and cellular longevity that could lead to rationally-designed gene circuits that slow aging,” the researchers note in their study.

During their research, the team studied Saccharomyces cerevisiae yeast cells as a model for the aging of human cells. They developed and employed microfluidics and time-lapse microscopy to track the aging processes across the cell’s lifespan.

In the current study, yeast cells that were synthetically rewired and aged under the direction of the synthetic oscillator device resulted in an 82% increase in lifespan compared with control cells that aged under normal circumstances. The results revealed “the most pronounced lifespan extension in yeast that we have observed with genetic perturbations,” they noted.

“Our oscillator cells live longer than any of the longest-lived strains previously identified by unbiased genetic screens,” said Hao.

“Our work represents a proof-of-concept example, demonstrating the successful application of synthetic biology to reprogram the cellular aging process,” the authors wrote, “and may lay the foundation for designing synthetic gene circuits to effectively promote longevity in more complex organisms.”

The team is currently expanding their research to the aging of diverse human cell types, including stem cells and neurons.