Despite the impressive power of the immune system’s complex defense network, one type of threat is especially challenging to combat. This arises when the body’s own native cells turn rogue, leading to the phenomenon of cancer. Although the immune system often engages to try to rid the body of malignant cells, its efforts are frequently thwarted as the disease progresses unchecked.The illustration shows a cancer cell (center) surrounded by immune T-cells augmented with an oncolytic (cancer-fighting) virus. A new study describes how a combination of immunotherapy and virotherapy, using myxoma virus, provides new hope for patients with treatment resistant cancers.

In new research appearing in the journal Cancer Cell, corresponding authors Grant McFadden, Masmudur Rahman and their colleagues propose a new line of attack that shows promise for treatment-resistant cancers.

The approach involves a combination of two methods that have each shown considerable success against some cancers. The study describes how oncolytic virotherapy, a technique using cancer-fighting viruses, can act in concert with existing immunotherapy techniques, boosting the immune capacity to effectively target and destroy cancer cells.

Oncolytic viruses represent an exciting new avenue of cancer therapy. Such viruses have the remarkable ability to hunt and terminate cancer cells while leaving healthy cells unharmed, as well as enhancing the immune system’s ability to recognize and terminate cancer cells.

One such virus, known as myxoma, is the focus of the current research and an area of expertise for the research group. The study shows that the use of T-cells infected with myxoma virus can induce a form of cancer cell death not previously observed.

Known as autosis, this form of cell destruction may be particularly useful against solid tumors that have proven treatment-resistant to various forms of cancer therapy, including immunotherapy alone.

“This work affirms the enormous potential of combining virotherapy with cell therapy to treat currently intractable cancers,” McFadden says.

McFadden directs the Biodesign Center for Immunotherapy, Vaccines and Virotherapy at Arizona State University.

Internal sentries

The immune system is composed of a range of specialized cells designed to patrol the body and respond to threats. The system is involved in a ceaseless arms race against pathogens, which evolve sophisticated techniques to attempt to outwit immune defenses, propagate in the body and cause disease. Cancer presents a unique challenge to the immune system as tumor cells often lack the identifying cell features that allow the immune system to attack them by distinguishing self from non-self.

Cancer cells can further short-circuit immune efforts to hunt and destroy them, through a range of evasive strategies. Researchers hope to help the immune system to overcome cancer’s notorious tactics of disguise, developing new experimental techniques belonging to a category known as adoptive cell therapy, or ACT.

Such methods often involve removing a collection of cancer-fighting white blood cells known as T-cells, modifying their seek-and-destroy capacities and reinjecting them in patients. Two forms of ACT immunotherapy are described in the new study: CAR T-cell therapy (CART) and T Cell Receptor Engineering (TCR). The basic idea in each case is the same: treating cancer with activated T lymphocytes extracted from the patient.

New method delivers one-two punch to tumor cells

The development of these therapies has been nothing short of revolutionary, and some cancer patients facing grim prospects have made remarkable recoveries following the use of immunotherapy. But techniques like CART and TCR nevertheless have their limitations and are often ineffective against advanced solid tumors. In such cases, cancer cells often manage to evade destruction by T-cells by downregulating or losing the surface antigens or MHC proteins that T-cells use to identify them.

The new study highlights the ability of immunotherapy when it is coupled with virotherapy to break through the wall of cancer resistance, specifically using myxoma-equipped T-cells. The myxoma can target and kill cancer cells directly but more usefully can induce an unusual form of T-cell directed cell death known as autosis. This form of cell death augments two other forms of programmed cancer cell death induced by T-cells, known as apoptosis and pyroptosis.

During myxoma-mediated autosis, cancerous cells in the vicinity of those targeted by the therapy are also destroyed in a process known as bystander killing. This effect can considerably enhance the dual therapy’s aggressive eradication of cancer cells, even in notoriously hard-to-treat solid tumors.

A combined myxoma-immunotherapy approach therefore holds the potential to turn so-called “cold tumors,” which fly under the immune system’s radar, into “hot tumors” that immune cells can identify and destroy, allowing CAR T-cells or TCR cells to enter the tumor environment, proliferate and activate.

“We are at the edge of discovering newer aspects of the myxoma virus and oncolytic virotherapy,” Rahman says. “In addition, these findings open the door for testing cancer-killing viruses with other cell-based cancer immunotherapies that can be used in cancer patients.”

The ability to radically reengineer oncolytic viruses like myxoma to target a range of resistant cancers provides a new frontier for the treatment of this devastating disease.

In a first-of-its-kind study funded by the National Science Foundation awarded to professor Daniel Costa (lead PI; UCSC), associate professor Stephen Trumble, Ph.D. (Baylor), professor Shane Kanatous, Ph.D. (Colorado State University), wildlife biologist Mike Goebel, Ph.D. (NOAA), and professor Daniel Crocker, Ph.D. (Sonoma State University), the PIs and Kienle (a graduate student and postdoctoral researcher at the time) set out with one shared goal: to learn more about leopard seals. Over the course of two years, the research group studied 22 leopard seals off the Western Antarctic Peninsula, an area rapidly warming and changing. They weighed and measured each seal and followed each seal’s activities and dive patterns using satellite/GPS tags.

In the study published in Frontiers of Marine Science — “Plasticity in the morphometrics and movements of an Antarctic apex predator, the leopard seal” — Kienle (first author) and the team documented the flexible behaviors and traits that may offer leopard seals the resilience needed to survive the extreme climate and environmental disturbances occurring around Antarctica.

This study greatly increases our understanding of leopard seals’ life history, spatial patterns and diving behavior,” Kienle said. “We show that these leopard seals have high variability (or, flexibility) in these different traits. Across the animal kingdom, variability is vital for animals adapting and responding to changes in their environment, so we’re excited to see high variability in this Antarctic predator.”

Among the research team’s discoveries detailed in the journal article:

Adult female leopard seals are much larger than adult males; in fact, females are 1.5 times larger and longer.

• The team measured one of the largest leopard seals ever, an adult female they nicknamed “Bigonia,” who weighed 540 kg (1,190 lbs.).
• Female-biased sexual dimorphism (where females are larger) is unusual among marine mammals, a diverse group that includes polar bears, whales, dolphins, seals and sea lions, but leopard seals are the most extreme example of female-biased dimorphism among the 130+ species of marine mammals.
• Why females are larger than males is not known, although Kienle explained other studies show that larger females are better at defending feeding areas, as well as stealing prey from smaller seals. Larger females also eat bigger, energy-rich prey, including fur seals and penguins, while males and smaller females often eat smaller prey like krill and fish. This suggests that the larger body size in adult females is beneficial and offers a selective advantage that Kienle and team will continue to explore.

From the movement data, female leopard seals spent more time “hauled out” — or coming out of the water to rest on ice or land — than males.

• Two adult female leopard seals in this study spent two weeks straight hauled-out on ice in the middle of the ocean, not eating and not getting in the water. Kienle and colleagues suggest that this two-week haul-out period is when female leopard seals give birth and nurse their pup.
• At the end of the two weeks, females return to water and begin diving for food again, and, at the same time, they likely wean their pup. It’s a short period to spend with their pups because the leopard seal is doing all of these really energetically demanding things without any food.

Male and female leopard seals swim short and long distances in both coastal and open-ocean habitats.

• One seal only traveled 46 km from where the team worked with the seal, staying in and around islands off the Antarctic Peninsula.
• Another seal, however, traveled 1,700 km during that same period away from the tagging location, swimming to an island more than a thousand kilometers away.

Leopard seals of both sexes are short, shallow divers — diving to an average of 30 meters and taking three-minute-long dives.

• Other seals can dive thousands of meters deep and hold their breath for more than 40 minutes. However, the research team recorded the longest and deepest dive ever recorded for leopard seals made by a male nicknamed “Deadpool,” who dove to 1,256 meters for 25 minutes.

“It’s interesting to see such variation [in movements and dive behavior] in a relatively small number of animals. To me, this means that leopard seals are highly flexible in their movement patterns, and that’s a really good thing in terms of adapting to changes in your environment,” Kienle said.

What’s next for this team of leopard seal biologists? Kienle said the team continues to analyze additional data from these same 22 leopard seals for publication. Kienle also is excited to compare how the leopard seals from this study compare to other populations of leopard seals across the Southern Ocean.

“I have so many more questions, and I’m excited to continue learning about leopard seals for years to come. There’s so much more to discover about this incredible Antarctic predator,” said Kienle, who leads the Comparative Ecophysiology of Animals Lab at Baylor that focuses on understanding how different animals work in the context of their environment.

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This framework or model takes low-cost data about relatively abundant species in a community and uses it to generate valuable insights on their harder-to-find neighbors. The journal Conservation Biology published the research as an Early View article on Aug. 25.

“One of the biggest challenges in monitoring biodiversity is that the species you’re most concerned about tend to be lowest in abundance or they’re the hardest species to observe during data collection,” said Matthew Farr, the lead author on the new report. “This model can be really helpful for those rare and elusive species.”

Farr, now a postdoctoral researcher at the University of Washington, helped develop the model as a doctoral student in Elise Zipkin’s Quantitative Ecology Lab in the College of Natural Science at MSU.

“There are a lot of species in the world and many of them are data deficient,” said Zipkin, an associate professor of integrative biology and director of MSU’s Ecology, Evolution and Behavior Program, or EEB. “We’re developing approaches to more quickly estimate what’s going on with biodiversity, which species are in trouble and where, spatially, do we need to focus our conservation efforts.”

After validating the model with an assist from forest-dwelling antelope in Africa, the researchers say it could be applied to a variety of other animals that meet certain criteria.

“The model doesn’t work for all types of species. It’s not a panacea,” Zipkin said. “But when it does work for a community, we can learn a lot more about member species without much data.”

The ‘magic’ of the model

For its newest model, Zipkin’s team focused on what’s called detection-nondetection data that tracks whether or not a given animal is detected in a given habitat.

“It’s basically the cheapest data and the easiest to collect,” Zipkin said. “You go to a spot, wait and see what animals are there and only need to record which species are seen.”

Researchers gather this data visually in person or with low-cost, motion-detecting camera traps that snap photos when triggered by an animal. Researchers then analyze the photos to record detection-nondetection data over time.

There are trade-offs, though. Although relatively cheap and easy to collect, detection-nondetection data doesn’t provide as much information as researchers and conservationists want. Historically, that has required intensive observational approaches such as tagging and tracking animals.

“That lets us calculate all sorts of things about the animals and their communities, but that data is expensive and hard to get,” Zipkin said. “For certain species, it’s impossible.”

The MSU team realized that, for the right animals, they could use an understanding of animal behavior and statistics to close the information gap by squeezing more insight out of detection-nondetection data.

“For some species, these are the best data you can get,” Farr said. “Now we can get more out of it.”

That may sound like magic — some of Zipkin’s colleagues have even said so — ?but there’s nothing supernatural about the model. Like much of science, it’s the result of hard work, collaboration and building on previous efforts in the field.

The story of the new model has its roots in 2003 with researchers J. Andrew Royle and James D. Nichols. The duo devised a mathematical link between the abundance of a species and the probability of detecting it.

At the time, Royle was a researcher with the U.S. Fish and Wildlife Service and Nichols was with the U.S. Geological Survey. Both are MSU alumni: Royle graduated with his bachelor’s degree in 1990 and Nichols earned his doctorate in 1976.

“It’s interesting,” said Farr, whose current adviser, Sarah Converse, also graduated with a bachelor’s degree from Michigan State before becoming an associate professor at the University of Washington. “Wherever you go in this field, people have some connection to Michigan State.”

After publishing the Royle-Nichols model, Royle joined the USGS, where he’d work with Zipkin before she joined MSU in 2014. In 2016, Zipkin’s team evolved the Royle-Nichols model to estimate things like the survival and reproduction rates for a single species using the barred owl as a case study.

Working in Zipkin’s lab with support from the National Science Foundation, Farr took the next step by linking the population dynamics of different species within the same communities.

“The model lets information from more common species inform what’s happening with the rare and elusive species,” said Farr. “The model relies on the commonalities between species, but still allows for variations.”

To develop the model, the team had to make some assumptions, like that the target species were territorial and did not travel much. The researchers then had to find real species that fit those assumptions to validate their model.

“We knew it would work for certain types of communities, but did those communities exist in real life?” Zipkin said.

“That’s one of the biggest challenges in model development,” Farr said. “You develop the model in a vacuum with simulations running under perfect conditions. You need to show what it can do in a real-world situation.”

“That’s when Tim O’Brien reached out and said, ‘I have your animals,'” Zipkin said.

The duiker data

Timothy O’Brien is a retired ecologist in Kenya who worked with the Wildlife Conservation Society, a nongovernmental organization or NGO, and an expert in camera traps. As part of what’s known as the Tropical Ecology Assessment and Monitoring program, or TEAM, he’s helped standardize how camera traps are used to make their data as powerful as possible.

He was familiar with Zipkin’s 2016 work and learned that she was expanding the model to include multiple species over multiple seasons. He suspected that forest-dwelling antelopes, notably those known as duiker, would provide the perfect test case.

Not only did duiker behavior match the assumptions of the model, but O’Brien had been helping monitor the animals for years using camera traps. Duikers presented an interesting and important conservation case.

“The duiker that live in rainforests, they are the most sought-after bushmeat in Africa,” O’Brien said. “If duiker populations are in decline, it’s usually because of people hunting for bushmeat.”

Bushmeat is meat from any wild animal and it’s an important source of food and income for many communities. But the hunting is loosely regulated and is financially incentivized by markets that sell bushmeat. The combination can be devastating for duiker populations.

With MSU’s model and TEAM’s duiker data, the team assessed the population dynamics of a total of 12 antelope species — some more abundant than others — in six national parks in Africa, where duikers are protected. The data covered time periods ranging from four to 11 years.

“We didn’t see the level of population decline in duiker you expect to see when hunting is an issue,” O’Brien said. “I would say the parks are fulfilling their function as far as duiker are concerned.”

Overall, the duiker populations were mostly stable, but the researchers did detect population declines in about 20% of the combinations of species and parks that they examined. Again, the declines weren’t so substantial to suggest that the duiker were being overhunted in the parks, but the researchers still want to understand what’s happening in those cases.

“We found that’s what causing the changes was more the differences between the parks than between the species,” Zipkin said. “We haven’t pinpointed the exact causes yet, but our results could help us do that.”

“Matt and Elise have taken this model to a whole new plane,” O’Brien said. “I’ve really enjoyed the collaboration.”

Charles Yackulic, a research statistician with the USGS, was also a contributor to the project, which was supported by NSF, WCS, Conservation International, the Smithsonian Institution and the Gordon and Betty Moore Foundation.

“This project is a great example of a university, government and NGOs working together,” Zipkin said.

On the heels of the Aug. 16 bill-signing ceremony at the White House, a new University of Michigan study finds that making the switch to all-electric mail-delivery vehicles would lead to far greater reductions in greenhouse gas emissions than previously estimated by the USPS.

In its analysis of the potential environmental impacts of the Next Generation Delivery Vehicle program, the Postal Service underestimated the expected greenhouse gas emissions from gasoline-powered vehicles and overestimated the emissions tied to battery-electric vehicles, according to U-M researchers.

“Our paper highlights the fact that the USPS analysis is significantly flawed, which led them to dramatically underestimate the benefits of BEVs, which could have impacted their decision-making process,” said Maxwell Woody, lead author of the new study, published online Aug. 26 in the peer-reviewed journal Environmental Science & Technology.

The NGDV program calls for the purchase of up to 165,000 new mail delivery trucks over the next decade. The Postal Service said in February that at least 10% of the new mail trucks would be electric. But following blistering criticism from many quarters, the agency upped that number in July.

Though the Postal Service now says at least 40% of the new delivery vehicles will be electric, the flaws in the USPS environmental analysis remain and need to be addressed, said Woody, a research area specialist at the Center for Sustainable Systems, which is part of the U-M School for Environment and Sustainability.

The new study takes a second look at the two delivery-vehicle scenarios the Postal Service evaluated in its 340-page Final Environmental Impact Statement on the NGDV project, published Jan. 7.

That document compared the expected environmental impacts of a delivery fleet with 10% battery-electric vehicles and 90% gasoline-powered trucks (called the ICEV scenario for internal-combustion engine vehicles) to a fleet with 100% battery-electric vehicles (called the BEV scenario).

U-M researchers conducted a cradle-to-grave greenhouse-gas emissions assessment — known as a life-cycle assessment, or LCA — of the two scenarios and reached some vastly different conclusions than the Postal Service did.

The U-M team determined that:

• Lifetime greenhouse gas emissions under the ICEV scenario would be 15% higher than estimated by the Postal Service, while emissions tied to the BEV scenario would be at least 8% lower than estimated by the agency.
• When anticipated improvements to electric vehicles and future electrical-grid decarbonization are factored in, a fully electric USPS delivery fleet would result in up to 63% lower greenhouse gas emissions than the agency estimated, over the lifetime of the fleet.
• An all-electric fleet would reduce lifetime greenhouse gas emissions by 14.7 to 21.4 million metric tons of carbon dioxide equivalents when compared to the ICEV scenario. The USPS estimate was 10.3 million metric tons.

The Postal Service declined to comment on the U-M study.

In February, the agency announced it had completed the environmental review for its Next Generation Delivery Vehicle program and was moving ahead with plans to start purchasing the new trucks. At least 10% of the delivery vehicles would be zero-emissions electric models, while the remainder would be powered by gasoline.

In response, attorneys general from 16 states (including Michigan), the District of Columbia and several environmental groups sued the mail agency to block the original purchase plan or to force the Postal Service to buy more electric trucks. The agency later pledged to electrify at least 40% of its new delivery fleet.

The authors of the new study say the main reasons their findings differ substantially from the USPS results are:

• The U-M study includes greenhouse gases generated throughout a delivery vehicle’s lifetime, including the mining and manufacturing of materials, vehicle assembly, vehicle operations and service (known as use-phase emissions) and end-of-life disposal. The Postal Service analysis looked only at use-phase emissions.
• The new study includes projections of how electrical-grid emissions are likely to change over the estimated 20-year service life of next-generation delivery vehicles, as renewables increasingly replace fossil fuels. The USPS analysis did not address this factor, which is known as grid decarbonization.
• The U-M study uses a more accurate method to calculate vehicle operating emissions, one that relies on fuel economy and fuel combustion intensity rates. The USPS analysis of projected operating emissions was based on estimated per-mile emissions rates.

“While our emissions results and USPS emissions values are on the same order of magnitude, the details of the USPS FEIS seem to have significant miscalculations and vary greatly from the established literature on vehicle LCAs,” the study’s authors wrote.

Study senior author Greg Keoleian said the new findings suggest the Postal Service should be deploying electric delivery trucks at a rate much higher than 40%. The failure to do so exposes a lack of sustainability leadership by the agency, he said.

Many of the largest private fleet operators — including FedEx, UPS, Amazon and Walmart — have begun electrifying their fleets and have more ambitious electrification and decarbonization targets than the current USPS purchase plan, he said.

“Each gas vehicle purchased locks in infrastructure for at least 20 years, which will cause the federal government to fall behind private vehicle fleets and will drive future greenhouse gas emissions that could be dramatically reduced by greater electric delivery vehicle deployment,” said Keoleian, director of the U-M Center for Sustainable Systems.

Ultimately, the USPS decision about next-generation delivery vehicles was based more on cost than climate-altering greenhouse gas emissions, he said. The agency estimated that an all-electric delivery fleet would have a total cost of ownership about $3.3 billion higher than a fleet with just 10% electric vehicles.

However, the recently signed U.S. Inflation Reduction Act includes $3 billion to help the U.S. Postal Service meet zero-emission vehicle goals: $1.29 billion for the purchase of zero-emission delivery vehicles and $1.71 billion for infrastructure to support those vehicles.

The additional funds will likely reduce cost-based objections to a fully electric postal delivery fleet.

On top of that, the authors of the new study say the mail agency’s estimate of a $3.3 billion cost savings for the ICEV scenario failed to account for the climate and public health damages associated with continued use of fossil fuel-powered vehicles.

“Given the long lifetimes expected of these vehicles, committing to such a course contradicts U.S. climate policy and environmental justice goals, squanders an opportunity to deploy BEVs in an ideal use case, exposes a lack of sustainability leadership, and jeopardizes our ability to meet national and international climate targets,” the study authors wrote.

In addition to Woody and Keoleian, the authors of the Environmental Science & Technology paper are Parth Vaishnav and Michael Craig of the Center for Sustainable Systems at the U-M School for Environment and Sustainability.

The work was supported by Ford Motor Co. through a Ford-University of Michigan Alliance Project Award, by the Responsible Battery Coalition and by the U-M School for Environment and Sustainability.

In mammals, the answer is many times, and often in a surprising way, according to a new study on proteins called mucins. These molecules have a variety of functions, but as a family, they are known as components of mucus, where they contribute to the substance’s gooey consistency.

Through a comparison of mucin genes in 49 mammal species, scientists identified 15 instances in which new mucins appear to have evolved through an additive process that transformed a non-mucin protein into a mucin.

The scientists propose that each of these “mucinization” events began with a protein that wasn’t a mucin. At some point, evolution tacked a new section onto this non-mucin base: one consisting of a short chain of building blocks called amino acids that are decorated with sugar molecules. Over time, this new region got duplicated, with multiple copies added on to elongate the protein even further, making it a mucin.

The doubled regions, called “repeats,” are key to a mucin’s function, say University at Buffalo researchers Omer Gokcumen and Stefan Ruhl, the senior authors of the study, and Petar Pajic, the first author.

The sugars coating these sections protrude outward like the bristles of a bottle brush, and they bestow mucins with the slimy property that’s vital to many important tasks that these proteins carry out.

The research will be published on Aug. 26 in Science Advances.

“I don’t think it was previously known that protein function can evolve this way, from a protein gaining repeated sequences. A protein that isn’t a mucin becomes a mucin just by gaining repeats. This is an important way that evolution makes slime. It’s an evolutionary trick, and we now document this happening over and over again,” says Gokcumen, PhD, associate professor of biological sciences in the UB College of Arts and Sciences.

“The repeats we see in mucins are called ‘PTS repeats’ for their high content of the amino acids proline, threonine and serine, and they aid mucins in their important biological functions that range from lubricating and protecting tissue surfaces to helping make our food slippery so that we can swallow it,” says Stefan Ruhl, DDS, PhD, interim dean of the UB School of Dental Medicine and professor of oral biology. “Beneficial microbes have evolved to live on mucus-coated surfaces, while mucus can at the same time also act as a protective barrier and defend against disease by shielding us from unwanted pathogenic intruders.”

“Not many people know that the first mucin which had been purified and biochemically characterized came from a salivary gland,” Ruhl adds. “My lab has been studying mucins in saliva for the last 30 years, mostly because they protect teeth from decay and because they help balance the microbiota in the oral cavity.”

The intriguing evolution of an ‘amazing life trait’

“I think this paper is really interesting,” Gokcumen says. “It’s one of those times where we got lucky. We were studying saliva, and then we found something that’s interesting and cool and decided to look into it.”

While studying saliva, the team noticed that a small salivary mucin in humans called MUC7 was not present in mice. The rodents did, however, have a similarly sized salivary mucin called MUC10. The scientists wanted to know: Were these two proteins related from an evolutionary perspective?

The answer was no. But what the research uncovered next was a surprise. While MUC10 did not appear to be related to MUC7, a protein found in human tears called PROL1 did share a portion of MUC10’s structure. PROL1 looked a lot like MUC10, minus the sugar-coated bottlebrush repeats that make MUC10 a mucin.

“We think that somehow that tear gene ends up repurposed,” Gokcumen says. “It gains the repeats that give it the mucin function, and it’s now abundantly expressed in mouse and rat saliva.”

The scientists wondered whether other mucins might have formed the same way. They began to investigate and discovered multiple examples of the same phenomena. Though many mucins share common ancestry among various groups of mammals, the team documented 15 instances in which evolution appeared to have converted non-mucin proteins into mucins via the addition of PTS repeats.

And this was “with a pretty conservative look,” Gokcumen says, noting that the study focused on one region of the genome in a few dozen mammal species. He calls slime an “amazing life trait,” and he’s curious whether the same evolutionary mechanism might have driven the formation of some mucins in slugs, slime eels and other critters. More research is needed to find an answer.

“How new gene functions evolve is still a question we are asking today,” says Pajic, a UB PhD student in biological sciences. “Thus, we are adding to this discourse by providing evidence of a new mechanism, where gaining repeated sequences within a gene births a novel function.”

“I think this could have even broader implications, both in understanding adaptive evolution and in possibly explaining certain disease-causing variants,” Pajic adds. “If these mucins keep evolving from non-mucins over and over again in different species at different times, it suggests that there is some sort of adaptive pressure that makes it beneficial. And then, at the other end of the spectrum, maybe if this mechanism goes ‘off the rails’ — happening too much, or in the wrong tissue — then maybe it can lead to disease like certain cancers or mucosal illnesses.”

The study on mucins demonstrates how a long-time partnership between evolutionary biologists and dental researchers at UB is yielding new insights into genes and proteins that are also important to human health.

“My team has been studying mucins for many decades, and my collaboration with Dr. Gokcumen has brought this research to a new level by revealing all these exciting novel insights into their evolutionary genetics,” Ruhl says. “At this advanced stage of my career, it is also immensely gratifying to see that the flame of scientific curiosity is being carried on by a new generation of young investigators like Petar Pajic.”

Additional research co-authors include Shichen Shen, PhD, postdoctoral associate, and Jun Qu, PhD, professor, both in the Department of Pharmaceutical Sciences in the UB School of Pharmacy and Pharmaceutical Sciences, and in the UB Center of Excellence in Bioinformatics and Life Sciences; and Alison J. May, PhD, former postdoctoral scholar, and Sarah Knox, PhD, associate professor, both in the Department of Cell and Tissue Biology in the University of California, San Francisco School of Dentistry. May is now an assistant professor at the Icahn School of Medicine at Mount Sinai.

Scientists who conducted the study are supported by the U.S. National Science Foundation, along with the National Institute of Dental and Craniofacial Research and National Cancer Institute, both part of the U.S. National Institutes of Health.

In a new study, scientists from UEA, Portugal and Brazil used network theory to understand how insular habitat fragmentation affects tropical forest biodiversity. This approach perceives habitat patches and species as connected units at the whole-landscape scale, encompassing a species-habitat network. 

The study, “Emergent properties of species-habitat networks in an insular forest landscape,” is published today in the journal Science Advances. 

The authors studied 22 habitat patches, consisting of forest islands and three continuous forest sites, which were created by the Balbina Hydroelectric Reservoir, one of the largest in South America. The 608 species surveyed represented eight biological groups: mid-sized to large mammals; small non-flying mammals; understorey birds; lizards; frogs; dung beetles; orchid bees and trees. 

The study revealed widespread species extinction, especially of large-bodied species, but this varied across different groups of plants, vertebrates and invertebrates. Island size determined the persistence of species diversity, with just a few islands holding the most diversity.  

Large tracts of tropical forests become rarer as they are subdivided and isolated into small habitat patches. The removal of larger forest sites will exert the greatest impact, likely inducing secondary extinctions of species that occur only at a single site or those that have larger spatial requirements.  

Conversely, small forest patches proportionally harbour more species than one or a few larger patches of equal total area, so the loss of smaller sites is also expected to cause secondary extinctions.  

Prof Carlos Peres, co-author of the study, is Professor of Environmental Studies at UEA. He said: “Tropical developing countries are still hellbent on creating vast hydropower reservoirs under the banner of ‘green’ energy.  

“This is a double-jeopardy because we lose both the unique lowland biodiversity and the carbon stocks of the now inundated old-growth forests. 

“Such actions also generate a powerful methane pump, never mind the huge financial costs of mega-dams compared to diffuse in-situ electrification based on low-impact renewables.  

“We need a much better strategic dialogue between sustainable energy security and biodiversity conservation, particularly in the world’s most biodiverse emergent economies.” 

Dr Ana Filipa Palmeirim, a researcher from CIBIO-University of Porto, led the study, which investigated a complex landscape as a single unit. She said: “This approach allowed us to unveil previously unknown patterns, such as the simplification of the network structure and changes in important network parameters due to the loss of species affected by the dam.” 

Dr Carine Emer, a co-author of the study from the Rio de Janeiro Botanical Garden, said: “The beauty of this study lays in the combination of sophisticated network and statistical analyses, with the natural history of high-quality species inventories from an astonishing tropical living lab.  

“More than 3,000 islands were created 35 years ago due to the Uatumã River damming, and by studying these we were able to understand the functioning of such a complex and rich human-modified landscape.”  

The study was a collaboration between UEA in the UK; the Research Centre in Biodiversity and Genetic Resources (CIBIO) and the University of Porto, in Portugal; the Research Institute of the Rio de Janeiro Botanical Garden; the State University of Santa Cruz; the State University of Mato Grosso; and the Farroupilha Federal Institute of Education, Science and Technology, in Brazil. The study would not be possible without the logistical support provided by the staff of the Biological Reserve (REBIO) of Uatumã.