Associate Professor Manisha Pandey, Professor Michael Good, and their team from Griffith University’s Institute for Glycomics, are leading the development of a Strep A vaccine which is currently in Phase 1 clinical trials in Canada and quickly advancing to Phase 2 efficacy trials.

The team’s new preclinical research, recently published in Nature Communications, shows an experimental liposome-based vaccine approach incorporating a conserved M-protein epitope from Strep A and an immunostimulatory glycolipid (3D(6-acyl) PHAD) administered via the nasal passage, can provide long-term mucosal protection against Strep A.

Lead author Dr Victoria Ozberk said studies have shown most pathogens enter or colonise via the soft tissue in the upper respiratory tract, which is essentially the highway to the rest of the body.

“This has the potential to be a world-first as there are currently no subunit vaccines that target the upper respiratory tract due to a lack of licenced immunostimulants suitable for human use,” Dr Ozberk said.

“We demonstrated that a liposomal mucosal vaccination strategy can induce robust local protective immunity.”

Associate Professor Pandey said the team found PHAD plays an augmenting role in inducing enduring humoral and cellular immunity, which was evident for at least one-year post-vaccination.

“The longevity of immune response is a critical hallmark of successful vaccination and therefore the findings from this study are highly significant,” she said.

Professor Good said: “In the future, this vaccine platform could pave the way for other mucosal pathogens.”

Group A Streptococcus is a global human pathogen that leads to a wide range of infections from illnesses such as mild pharyngitis and impetigo to invasive diseases such as toxic shock syndrome, necrotising fasciitis, and cellulitis.

Professor Mark von Itzstein AO, Director of the Institute for Glycomics, welcomed these research findings.

“This platform provides a real shot at developing a new direction for vaccine discovery against significant infectious pathogens that cause serious and life-threatening diseases,” he said.

Immunity to Strep A takes several years to develop, and currently, there is no vaccine available.

Moreover, repeated infections can lead to the post-streptococcal sequelae of rheumatic fever and rheumatic heart disease, for which the Australian Indigenous population bears the highest disease burden globally.

Strep A causes 700 million human infections each year and there are more than 500,000 deaths globally.

The team has developed a Strep A vaccine which is currently being tested in a human clinical trial in Canada.

The paper ‘A Glycolipidated-liposomal peptide vaccine confers long-term mucosal protection against Streptococcus pyogenes via IL-17, macrophages and neutrophils’ has been published in Nature Communications.

The team of University of Illinois and Princeton University researchers created a cost-effective, end-to-end pipeline for this valuable organic acid by engineering a tough, acid-tolerant yeast as the fermenting agent, avoiding costly steps in downstream processing. Succinic acid is a widely used additive for food and beverages and has diverse applications in agricultural and pharmaceutical products.

This same pipeline can be used to produce other industrially important organic acids targeted by CABBI in its work to develop sustainable biofuels and biochemicals from crops, said co-author Huimin Zhao, CABBI’s Conversion Theme Leader and Professor of Chemical and Biomolecular Engineering (ChBE) at Illinois. To reduce reliance on fossil fuels, Conversion researchers are deploying microbes to convert plant biomass into chemicals used in everyday products as an alternative to conventional petroleum-based production.

“This will serve as a blueprint for all the other metabolic engineering products in CABBI,” said Zhao, one of several CABBI principal investigators on the project. Other PIs included Vijay Singh, CABBI’s Deputy Director for Science & Technology, Distinguished and Founder Professor of Agricultural and Biological Engineering (ABE), and Executive Director of the Integrated Bioprocessing Research Laboratory (IBRL) at Illinois; Jeremy Guest, Associate Professor of Civil & Environmental Engineering (CEE) at Illinois and part of CABBI’s Sustainability Theme; and Conversion Deputy Theme Leader Joshua Rabinowitz, Professor of Chemistry and the Lewis-Sigler Institute for Integrative Genomics at Princeton.

The study, published in Nature Communications, is led by CABBI — a U.S. Department of Energy Bioenergy Research Center — and funded by BioMADE, a Manufacturing Innovation Institute with more than 230 member organizations around the country, including companies, universities, and nonprofit organizations. BioMADE was catalyzed by the U.S. Department of Defense and works to secure America’s future through bioindustrial manufacturing innovation, education, and collaboration.

The work builds on years of research on succinic acid production by Zhao and his colleagues using Issatchenkia orientalis, an unconventional yeast ideal for making organic acids.

I. orientalis has the unique ability to thrive in low-pH, or acidic, conditions. Most organisms require a neutral pH environment to survive, including Saccharomyces cerevisiae, a more conventional yeast, or Escherichia coli bacteria. Both have been used by companies and labs to produce succinic acid but proved to be too costly, so efforts to scale up production have failed, Zhao said.

Those microorganisms require the addition of a base to neutralize the toxic acidic conditions so they can continue making succinic acid. But that generates side products, such as gypsum or calcium sulfate, which have to be separated out at the end of the pipeline to purify the product, driving up downstream processing costs.

“One of the bottlenecks in the production of organic acids is the separation cost,” Zhao said. “We have to add a lot of base to keep the pH near neutral, between 6 to 7.”

With I. orientalis, however, “the organism lives happily at a pH of 3 to 4,” so the additives are not required, Zhao said. “In the end, that significantly reduces costs.”

The CABBI researchers also did extensive metabolic engineering to rewire I. orientalis to produce robust levels of succinic acid — higher than either S. cerevisiae or E. coli, he said. Using metabolic flux analysis from Rabinowitz’s lab, they identified the steps in the yeast’s metabolism that limited the production of succinic acid. One key roadblock: Native I. orientalis can’t utilize the sucrose from sugarcane. So an enzyme was added that could break down sucrose from the sugarcane juice into glucose and fructose to make succinic acid. Other genes were introduced to overproduce succinic acid.

Working with Singh’s group at IBRL, the team then scaled up succinic acid production using industrially relevant equipment to conduct an end-to-end integration of the process. The pilot-scale work showed the new strains could produce up to 110 g/L of succinic acid and, after batch fermentation and downstream processing, an overall yield of 64% — impressive results having commercial significance, Singh said.

The combination of higher production levels through genetic engineering and lower costs from the elimination of downstream separation makes the process “very attractive,” Zhao said. “That’s why the pipeline is so economical, at least at this pilot scale.”

The final step was working with Guest to simulate a full end-to-end, low-pH succinic acid production pipeline, using the open-source software platform BioSTEAM developed by his group. The techno-economic analysis (TEA) and life cycle assessment showed the process was financially viable and could reduce greenhouse gas emissions by 34% to 90% relative to fossil fuel-based production processes.

“These advancements in metabolic engineering could have large-scale benefits, simultaneously driving down costs and environmental impacts in support of a circular bioeconomy,” Guest said.

The process emits less carbon dioxide (CO₂) than conventional petroleum-based chemical processing. Plants like sugarcane also soak up carbon, and CO₂ can be used as a substrate for the process, further reducing its carbon footprint.

“It’s definitely more environmentally friendly. That’s the premise for all the research in CABBI: using renewable resources to make chemicals and fuels,” Zhao said.

Researchers plan further scale-up studies soon to support commercialization of the succinic acid production process.

The work will also be a template for production of other CABBI products using I. orientalis, including 3-hydroxypropionic acid (3-HP). The market for 3-HP, used in components of disposable diapers and sealants, exceeds $1 billion, and research to date shows huge promise, Zhao said.

“We expect I. orientalis can serve as a general industrial platform for the production of a wide variety of organic acids,” said Vinh Tran, primary author on the paper and a Ph.D. student in ChBE.

The project involved several lab groups and contributions from all three themes of CABBI’s research — using sugarcane juice from the Feedstock Production research team, metabolic research and bioprocessing facilities from the Conversion team, and economic and environmental analysis from the Sustainability team.

Co-authors included CABBI researchers Sarang Bhagwat of CEE and Yihui Shen of the Department of Chemistry at Princeton; Somesh Mishra of ABE; Saman Shafaei, Shih-I Tan, Zia Fatma, and Benjamin Crosly of ChBE; and Jayne Allen of CEE.

That’s the assertion made by an international group of scientists in one of four related research papers, all appearing in the journal Science Open: Airbursts and Cratering Impacts. The papers are the latest results in the investigation of the Younger Dryas Impact Hypothesis, the idea that an anomalous cooling of the Earth almost 13 millennia ago was the result of a cosmic impact.

“In this general region, there was a change from more humid conditions that were forested and with diverse sources of food for hunter-gatherers, to drier, cooler conditions when they could no longer subsist only as hunter-gatherers,” said Earth scientist James Kennett, a professor emeritus of UC Santa Barbara . The settlement at Abu Hureyra is famous among archaeologists for its evidence of the earliest known transition from foraging to farming. “The villagers started to cultivate barley, wheat and legumes,” he noted. “This is what the evidence clearly shows.”

These days, Abu Hureyra and its rich archaeological record lie under Lake Assad, a reservoir created by construction of the Taqba Dam on the Euphrates River in the 1970s. But before this flood, archaeologists managed to extract loads of material to study. “The village occupants,” the researchers state in the paper, “left an abundant and continuous record of seeds, legumes and other foods.” By studying these layers of remains, the scientists were able to discern the types of plants that were being collected in the warmer, humid days before the climate changed and in the cooler, drier days after the onset of what we know now as the Younger Dryas cool period.

Before the impact, the researchers found, the inhabitants’ prehistoric diet involved wild legumes and wild-type grains, and “small but significant amounts of wild fruits and berries.” In the layers corresponding to the time after cooling, fruits and berries disappeared and their diet shifted toward more domestic-type grains and lentils, as the people experimented with early cultivation methods. By about 1,000 years later, all of the Neolithic “founder crops” — emmer wheat, einkorn wheat, hulled barley, rye, peas, lentils, bitter vetch, chickpeas and flax — were being cultivated in what is now called the Fertile Crescent. Drought-resistant plants, both edible and inedible, become more prominent in the record as well, reflecting a drier climate that followed the sudden impact winter at the onset of the Younger Dryas.

The evidence also indicates a significant drop in the area’s population, and changes in the settlement’s architecture to reflect a more agrarian lifestyle, including the initial penning of livestock and other markers of animal domestication.

To be clear, Kennett said, agriculture eventually arose in several places on Earth in the Neolithic Era, but it arose first in the Levant (present-day Syria, Jordan, Lebanon, Palestine, Israel and parts of Turkey) initiated by the severe climate conditions that followed the impact.

And what an impact it must have been.

In the 12,800-year-old layers corresponding to the shift between hunting and gathering and agriculture, the record at Abu Hureyra shows evidence of massive burning. The evidence includes a carbon-rich “black mat” layer with high concentrations of platinum, nanodiamonds and tiny metallic spherules that could only have been formed under extremely high temperatures — higher than any that could have been produced by man’s technology at the time. The airburst flattened trees and straw huts, splashing meltglass onto cereals and grains, as well as on the early buildings, tools and animal bones found in the mound — and most likely on people, too.

This event is not the only such evidence of a cosmic airburst on a human settlement. The authors previously reported a smaller but similar event which destroyed the biblical city at Tall el-Hammam in the Jordan Valley about 1600 BCE.

The black mat layer, nanodiamonds and melted minerals have also been found at about 50 other sites across North and South America and Europe, the collection of which has been called the Younger Dryas strewnfield. According to the researchers, it’s evidence of a widespread simultaneous destructive event, consistent with a fragmented comet that slammed into the Earth’s atmosphere. The explosions, fires and subsequent impact winter, they say, caused the extinction of most large animals, including the mammoths, saber-toothed cats, American horses, and American camels, as well as the collapse of the North American Clovis culture.

Because the impact appears to have produced an aerial explosion there is no evidence of craters in the ground. “But a crater is not required,” Kennett said. “Many accepted impacts have no visible crater.” The scientists continue to compile evidence of relatively lower-pressure cosmic explosions — the kind that occur when the shockwave originates in the air and travels downward to the Earth’s surface.

“Shocked quartz is well known and is probably the most robust proxy for a cosmic impact,” he continued. Only forces on par with cosmic-level explosions could have produced the microscopic deformations within quartz sand grains at the time of the impacts, and these deformations have been found in abundance in the minerals gathered from impact craters.

This “crème de la crème” of cosmic impact evidence has also been identified at Abu Hureyra and at other Younger Dryas Boundary (YDB) sites, despite an absence of craters. However, it has been argued that the kind of shock-fractured quartz found in the YDB sites is not equivalent to that found in the large crater-forming sites, so the researchers worked to link these deformations to lower-pressure cosmic events.

To do so, they turned to humanmade explosions of the magnitude of cosmic airbursts: nuclear tests conducted at the Alamogordo Bombing Range in New Mexico in 1945 and in Kazakhstan, in 1949 and 1953. Similar to cosmic airbursts, the nuclear explosions occurred above ground, sending shockwaves toward Earth.

“In the papers, we characterize what the morphologies are of these shock fractures in these lower-pressure events,” Kennett said. “And we did this because we wanted to compare it with what we have in the shock-fractured quartz in the Younger Dryas Boundary, to see if there was any comparison or similarities between what we see at the Trinity atomic test site and other atomic bomb explosions.” Between the shocked quartz at the nuclear test sites and the quartz found at Abu Hureyra, the scientists found close associations in their characteristics, namely glass-filled shock fractures, indicative of temperatures greater than 2,000 degrees Celsius, above the melting point of quartz.

“For the first time, we propose that shock metamorphism in quartz grains exposed to an atomic detonation is essentially the same as during a low-altitude, lower-pressure cosmic airburst,” Kennett said. However, the so-called “lower pressure” is still very high — probably greater than 3 GPa or about 400,000 pounds per square inch, equivalent to about five 737 airplanes stacked on a small coin. The novel protocol the researchers developed for identifying shock fractures in quartz grains will be useful in identifying previously unknown airbursts that are estimated to recur every few centuries to millennia.

Taken together, the evidence presented by these papers, according to the scientists, “implies a novel causative link among extraterrestrial impacts, hemispheric environmental and climatic change, and transformative shifts in human societies and culture, including agricultural development.”

When analyzing legs, wings and fins for moving robots or animals in the real world, the mathematics looks fairly straightforward. Limbs with multiple sections of various lengths create different ratios for leverage, bodies with alternate shapes and sizes create drag coefficients and centers of mass, and feet, wings or fins of various shapes and sizes push on the world around them.

All of these options create more degrees of freedom in the final design. But until now, say the researchers, nobody was paying much attention to the timing of how they’re all working together.

“Minimizing the amount of work being done by varying the speed over the mover is an idea that’s been around a long time,” said Adrian Bejan, the J.A. Jones Distinguished Professor of Mechanical Engineering at Duke. “But varying the rhythm of that movement — the music of how the pieces move together over time — is a design aspect that has been overlooked, even though it can improve performance.”

The reasoning and mathematics exploring this thesis was published in a paper online August 28 in the journal Scientific Reports.

To illustrate his point in the paper, Bejan points to natural swimmers such as frogs or humans doing the breaststroke. Their swim gate is characterized by three time-intervals: a slow period of reaching forward, a fast period of pushing backward and a static period of coasting. For optimum performance, the lengths of time for those intervals typically go long, fast, long. But in certain situations — outracing or outmaneuvering a predator, for example — the ratios of those periods change drastically.

In the design of robots built to emulate dogs, fish or birds, incorporating different rhythms into their standard cruising movements can make their normal operations more efficient. And those optimal rhythms will, in turn, affect the choices made for all of the other pieces of the overall design.

The work builds on research Bejan published nearly 20 years ago, where he demonstrated that size and speed go hand-in-hand across the entire animal kingdom whether on land, in the air or under water. The physics underlying that work dealt with weight falling forward from a given animal’s height over and over again. In this paper, Bejan shows that his previous work was incomplete, and that all animals, robots and other moving things can further optimize their mechanics by adding an element of rhythm.

“You can — and indeed you should — teach rhythms of movements to competitive swimmers and runners looking for an edge,” Bejan said. “Rhythm increases the number of knobs you can turn when trying to move through the world. It is yet another example of how good design — whether made by humans or through natural evolution — is truly a form of art.”