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Greater bamboo lemurs wait in cages at Centre ValBio before being released into a large quarantine enclosure inside the Ranomafana National Park. Photo by Johanna Mitra
Members of Centre ValBio transfer 10 greater bamboo lemurs.
Members of Centre ValBio transfer 10 greater bamboo lemurs.
Members of Centre ValBio transfer 10 greater bamboo lemurs.
A greater bamboo lemur feeds on bamboo. Photo by Johanna Mitra

By Daniel Dunaief

Patricia Wright
Photo by Sam Levitan, Sam Levitan Photography

Patricia Wright isn’t getting much sleep these days.

Distinguished Professor in Anthropology at Stony Brook University, Wright recently orchestrated the translocation of 10 critically endangered greater bamboo lemurs to Ranomafana National Park, a park in Madagascar that she helped create and which has been named a UNESCO World Heritage Site.

The conservation effort, which Wright had been working on since 2014, is designed to lower the risk that this particular lemur, which weighs about six pounds and has grey brown fur and white ear tufts, will go extinct.

Short on bamboo, which, as their name suggests, is their primary food source, greater bamboo lemurs, which are down to as few as 1,000 individuals, have been eating manioc and raiding farmer’s rice paddies. The people who farm these crops have hunted the greater bamboo lemur and used slingshots to hurl stones at them. 

The lemurs “think the rice is perfectly great,” said Wright. Some of the Malagasy people have injured or killed these lemurs. Two of the translocated lemurs have eye injuries.

Wright, who is teaching at Stony Brook this spring, applied for permits from a number of government officials to get the effort approved. 

From Stony Brook, she has been managing the care of these lemurs, often long after she might otherwise be asleep. During an acclimation period, the lemurs live, eat and interact in a large cage near the research station Centre ValBio and will be released into the wild within the next few weeks.

“I’m up every night texting,” Wright said. “When anything comes up, I give my advice.”

She said the process of watching these lemurs from afar is akin to those early days of parenting.

“You drift off, sleep for a couple of hours then you have to wake up and answer this or that problem,” said Wright, whose work with lemurs has won her numerous awards, including the Indianapolis Zoo Prize. 

Bamboo chefs

Wright has considerable help in working with and protecting the greater bamboo lemurs. While the rare lemurs are guests at Centre ValBio (CVB), about a dozen people are working with them each day, with five people going out daily to collect bamboo to feed them.

When the lemurs first arrived, they fought at night. The caretakers discovered that these primates were searching for food. By providing more bamboo, the staff at CVB ended the evening conflicts.

Johanna Mitra, a recent Stony Brook University graduate and the Communications Officer at CVB, attended the capture of these lemurs and has had the opportunity to observe them interacting in the cage.

She watched as an adult lemur sat facing two juveniles. The adult pulled up the bamboo shoot and the three of them took turns gnawing on it. After eating for about half an hour, the juveniles cuddled with the adult females.

Collaboration efforts

In addition to relying on her past experience working with primates at Duke University in the 1980’s and 1990’s, Wright collaborated with Dr. Mónica Ramírez, IUCN Species Survival Commission-Specialist, who is an expert in the relocation of woolly monkeys in Colombia.

Ramírez urged Wright to transport the monkeys in separate cages to reduce stress and overcrowding during the journey. Ramírez also wanted to ensure that the monkeys could see and hear each other. She recommended constant monitoring during transport. Stress could reduce how much food they ate.

Despite the lengthy journey, the lemurs traveled comfortably and ate along the way. Ramírez said that translocations can and often are emotionally taxing for conservationists.

“When I started working with translocations, it was so difficult for me to maintain calm because there are many factors that one cannot control, mainly after the release,” she explained.  “We do our best to guarantee the welfare of the individuals and the people involved.”

Bigger picture

In addition to the satisfaction of preventing a species on the brink of elimination from disappearing, Wright suggested that saving these lemurs could have numerous benefits. For one thing, these lemurs eat large quantities of bamboo, which contains cyanide. Such bamboo would be toxic to human systems. Learning how these animals tolerate and remove such a dangerous element could prove helpful.

Guides in Madagascar involved with the bio-tourism effort also appealed to Wright to save this species, which has unusual vocalizations that vary according to their circumstance. “It’s an important tourist attraction,” Wright said.

Questions on release

When Wright and her team release these translocated lemurs back into the wild, they recognize the enormous number of unknowns.

Predators such as fossa (pronounced “foo sah), hawks and eagles hunt lemurs. Fossa, which is a relative of the mongoose, hunt cooperatively.

Wright hopes the translocated lemurs “understand what a predator is” and take steps to stay alive.

Even before the release of these lemurs, Ranomafana National Park is home to one adult female greater bamboo lemur named Simone, who joined a social group with the golden bamboo lemur, which is half her size.

Wright doesn’t know how Simone, who grooms golden bamboo lemurs but doesn’t receive grooming from them in return, will react to her own species. “What happens when she finds out her own species are in the neighborhood?” Wright asked. “It’s going to be very exciting.”

She might encourage her new lemur family to attack or might ditch her adopted social group for the well-traveled members of her own species.

Ramirez suggested that recruiting and educating the public in conservation would increase the likelihood of its success.

“Involving the community in the project is essential to guarantee the security of both the people and the animals,” she said.

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Kyle Swentowsky in front of the maize fields at CSHL’s Upland Farm preserve. Photo courtesy of CSHL

By Daniel Dunaief

Farmers typically plant the sweet corn that fills Long Islander’s table some time between late April and June, with flavorful yellow kernels ready to eat about eight weeks later.

But what if corn, which is planted and harvested on a typical annual crop schedule, were perennial? What if farmers could plant a type of corn that might have deeper roots, would become dormant in the winter and then grew back the next year?

Kyle Swentowsky, holding corn on the north fork of Long Island.

Cold Spring Harbor Laboratory postdoctoral researcher Kyle Swentowsky, working in the lab of  Professor Dave Jackson, is interested in the genetics of perennial grasses, which includes maize, wheat, rice, barley, sorghum and others. He uses maize as a model.

Extending the work he did as part of his PhD research at the University of Georgia, Swentowsky, who arrived at CSHL in July of 2021, is searching for the genes that cause the major differences between annual and perennial grasses.

Kelly Dawe, who was Swentowsky’s PhD advisor, described him as “passionate” “diligent” and “thoughtful.” Dawe explained that perennials have been beneficial in the farming of other crops. Perennial rice has enabled farmers to save 58.1 percent on labor costs and 49.2 percent on input costs with each regrowth cycle, Dawe explained, adding, “The rice work is much farther along, but could have a similar impact on corn.”

Aside from producing crops over several years without requiring replanting, perennial corn also has several other advantages. Perennials, which have deeper roots, can grow in soil conditions that might not be favorable for annual crops, which can help stabilize the soil and expand the range of farmable land.

Recently, people have also considered how scientists or farmers might take some of the sub-properties of perennials and apply them to annual crops without converting them to perennials. Some annuals with perennial traits might stay green for longer, which means they could continue the process of photosynthesis well after annuals typically stop.

A complex challenge

Scientists have been trying to make perennial corn for about 50 years. The perennial process is not as simple as other plant traits.

“We don’t understand all the underlying sub properties of being perennial,” Swentowsky said. “It’s very complicated and involves a lot of regions in the genome. My work aims to get at some of these sub traits and genomic loci that are involved in this process.”

In his work, Swentowsky is interested in the sub traits that the major genes control. He expects that a reliable perennial corn wouldn’t make the annual variety obsolete. Even after researchers develop an effective perennial corn, farmers may still cultivate it as an annual in some environments.

In the bigger picture, Swentowsky, like other plant researchers at CSHL and elsewhere around the world, recognizes the challenge of feeding a population that will continue to increase while climate change threatens the amount of arable land.

Plant breeders need to continue to come up with ways to increase crop yield to boost food production, he suggested. While some people have considered dedicating resources to back up plans like astro-botany — or growing crops in space — Swentowsky suggested this was challenging and urged ongoing efforts to produce more food on Earth.

Impressed with the way Matt Damon’s character in the movie The Martian farms potatoes on the Red Planet, Swentowsky suggested that such an agricultural effort would be challenging on a large scale in part because of the extreme temperature variations.

As for work on Earth, perennial corn may also remove more carbon dioxide from the air, reducing the presence of greenhouse gases such as carbon dioxide.

Swentowsky cautioned that the idea of carbon farming is still relatively new and researchers don’t know what would make a good carbon farming plant yet. At this point, his work has involved breeding and back crossing corn plants. Once he develops a better idea of what genes are involved in the perennial life cycle, he will consider taking a trans-genetic approach or use the gene editing tool Crispr to test the effects of the involved genes.

Swentowsky expects that several genetic changes may be necessary to develop a perennial plant. He and others have mapped the master regulators of perenniality to three major genes. He believes it’s likely that dozens or even hundreds of other genes scattered throughout the genome play a small role influencing perennial sub-traits.

California roots

A current resident of Long Beach, Swentowsky grew up in Sacramento, California. He earned his undergraduate and master’s degrees at the University of California at Santa Barbara. After six years, he was “tired of perfect weather,” he laughed. He would sweat through football games in January, when it was 80 degrees amid a cloudless sky.

As an undergraduate, he took a plant development course and appreciated the elegant way scientists tested plants. His two favorite scientists are Gregor Mendel, whose pioneering pea work led to the field of modern genetics, and Barbara McClintock, a former CSHL scientist whose Nobel Prize winning research on corn led to an understanding of transposable elements, or jumping genes in which genes change position on a chromosome. 

Outside of the lab, Swentowsky enjoys traveling, including camping and backpacking, spending time on the beach, attending reggae, alternative, classic rock, hip hop and electric concerts and going to breweries. During the winter, his favorite beers are stout and porter. In warmer weather, he imbibes sour IPA.

Swentowsky doesn’t just study corn: he also enjoys eating it. One of his favorites is elote, or Mexican street corn. He grills the corn on a barbecue, covers it with mayonnaise and cotija cheese and sprinkles lyme or chili powder on it.

Swentowsky, who is funded through the summer of 2025 at CSHL, appreciates the opportunity to contribute to work that could support future farming efforts. He hopes that studying perenniality in corn could have future applications.

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Ogochukwu Enekwizu with a suite of instruments at Brookhaven National Laboratory to make and study soot-seeded clouds. Photo courtesy of BNL

By Daniel Dunaief

Combining forces to form a three-part team, they strive to understand processes that are as visually stunning and inspirational as they are complex and elusive.

Clouds, which are so important to weather and climate, are challenging to understand and predict, as numerous processes affect properties at a range of scales.

A team from Brookhaven National Laboratory has provided the atmospheric sciences community with a host of information that advances an understanding of clouds.

In the atmospheric sciences community, “we typically talk about the three legs of a stool: modeling/ theory; field measurements; and targeted laboratory studies,” explained Arthur Sedlacek, Chemist in the Environmental and Climate Science Department.

Sedlacek conducts field experiments by collecting air samples from clouds in a range of locations such as flying through wildfire plumes.

In the beginning of 2021, BNL added postdoctoral researcher Ogochukwu Enekwizu to bolster another leg of that stool. Enekwizu conducts the kind of laboratory studies that provide important feedback and data for the work of Sedlacek and cloud modelers like Nicole Riemer, Professor in the Department of Atmospheric Sciences at the University of Illinois-Urbana Champaign.

Enekwizu studies how soot aerosols from wildfires influence the lifetime and formation of clouds. She’s also investigating how soot-cloud interactions affect the absorption and scattering of light by soot particles.

Wildfires provide kindling for the climate, as fires release warming agents that contribute to increases in global temperatures which result in more wildfires. By determining how these smaller scale processes in soot affect clouds, Enekwizu can reduce the so-called error bars or level of uncertainty in the models other scientists create and that rely on the data she develops.

Enekwizu’s collaborators appreciate her contribution. As a modeler, Riemer suggested that Enekwizu’s work provided key information.

“While the microscale processes of soot restructure are incredibly complicated, [Enekwizu] was able to boil it down to a few simple parameters,” Riemer explained. “This makes it feasible to implement this process in a model like ours, which look at aerosol populations, not just a few individual particles. From there, we can come up with ways to implement this knowledge into climate models, which are still much more simplified than the model that we are developing.”

Sedlacek, who is her supervisor, suggested that Enekwizu’s work is “now on the cusp of answering important questions of how aerosols interact with clouds.” He descried her set up as “truly unique” and expects her results to inform the community about wildfire aerosol-cloud interactions and will offer guidance on other necessary field measurements.

In broader research terms, wildfires can be important for the ecosystem, as they remove decaying material, clear out underbrush, release nutrients back into the soil and aid the germination of seedlings

The increasing frequency, duration and intensity of these fires has been important to the scientific community. The general public has become increasingly aware of its importance as well, Enekwizu said.

Collaborations

Recruited to BNL by Sedlacek and Atmospheric Scientist Ernie Lewis, Enekwizu is considering collaborations with other researchers at BNL.

She has started speaking with scientists at the Center for Functional Nanomaterials about exploring soot microstructure in a planned joint collaboration with her New Jersey Institute of Technology PhD advisor Dr. Alexie Khakizov. For this effort, Enekwizu has been in discussions with Dmitri Zakharov, who is in charge of the environmental transmission electron microscope at the CFN.

She hopes to take samples and introduces forces under a controlled environment in the transmission electron microscope to see how that affects the structure of soot in fine detail.

Looking at the news with one wildfire event after another, Enekwizu feels compelled to conduct research in the lab and share data amid “a heightened sense of urgency to get this work done” and to share it with the world at large.

Scientific origins

Born in the southeastern part of Nigeria in Enugu and raised in Enugu, Lagos and Abuja, Enekwizu developed an interest in science at 13. She enjoyed classes in a range of sciences and said chemistry was her favorite.

“I knew I was not going to go into medicine because I was squeamish,” she said.

Chemical engineering fascinated her and also appeared to offer career opportunities.

During a chemical engineering internship, she worked at the Nigerian National Petroleum Corporation where she learned about flaring practices. It inspired her final year project on biogas as a renewable energy source and sparked her curiosity on the fate of pollutants and particulate matter that arise from legal and illegal flaring activities. 

In flaring, companies burn off excess gas to control pressure variations, increasing the safety of the operation at the expense of burning a potential resource.

When Enekwizu was at NJIT, Lewis, who is a longtime collaborator with Sedlacek, reached out to Khakizov to inquire about someone with a background in carbonaceous aerosols. After interviewing with Lewis, Sedlacek and others, Enekwizu received the job offer and began working in January of 2021.

A resident of Ridge, Enekwizu, who goes by the name “Ogo,” enjoys festivals and events around Long Island. She also appreciates the area’s ubiquitous beaches and has delighted in strawberry picking.

She hopes to explore Montauk later this spring or summer.

Mentoring

Enekwizu is passionate about mentoring students, particularly those who might be under represented in the field of Science, Technology, Engineering and Medicine.

She served as a graduate student mentor for Divyjot Singh, who was an undergrad at NJIT. Enekwizu taught Singh, who had grown up in Bhopal, India and had only been in the United States for six months when they met, “how to come up with research questions, how to develop hypotheses, how to write a proposal, how to make good presentations for conferences and everything in between,” he explained in an email.

While working with her, Singh found his passion for research and decided to pursue a PhD. 

Enekwizu is also passionate about supporting young women in science. She suggested that young black girls sometimes feel intimidated by STEM classes and careers. She urges a hands on approach to teaching and hopes to be a role model.

“If young girls see people like me thrive in STEM, they’ll be encouraged not to give up,” she said. “That is a huge win, in my opinion.”

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Nivea Pereira de Sa Photo by Rodrigo Carvalho da Silva

By Daniel Dunaief

When people are immunocompromised, exposure to what might ordinarily be a harmless fungus can cause significant health problems.

Researchers in the laboratory of Maurizio del Poeta, Distinguished Professor in the Department of Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University, have been looking to create new treatments and develop vaccines against these fungi.

Working with a team of scientists at Stony Brook, research scientist Nivea Pereira de Sa, who joined del Poeta’s lab in 2018 as a postdoctoral researcher, recently published research in the journal mBio about potential anti-fungal drugs that target a key enzyme in the fungus Aspergillus fumigatus. 

Without the enzyme, the fungus can’t cause disease and the host defenses have time to eliminate it even if the host is immunodeficient.

Working with Michael Airola, Assistant Professor in the Department of Biochemistry and Cell Biology at SBU, Pereira de Sa started out by trying to find the structure of sterylglucosidase, an enzyme that is a molecular key for the fungus during infection and that aids in its ability to adapt to environmental changes such as low oxygen levels and changes in pH.

Pereira de Sa learned how to do x-ray crystallography from Airola, a process that reveals the structure of compounds.

In an email, Airola described Pereira de Sa as an “expert” in the technique.

Airola called the research “one of the most exciting projects” he’s worked on and hopes the group can translate the results into the clinic. A talented biochemist, Pereira de Sa is also an “expert in so many different scientific areas,” Airola wrote, which he described as “rare.”

Pereira de Sa also determined the structure of the same enzyme for Cryptococcus, another invasive and potentially harmful fungus. The enzymes in both fungi have a high degree of similarity.

Pereira de Sa expressed satisfaction at the application of such work. “Every time I get a crystal structure, it’s so amazing,” she said. “I love doing that.”

Pereira de Sa started screening potential compounds to inhibit sterylglucosidase in Aspergillus,

Del Poeta’s lab coordinated the design and testing of these inhibitors with Iwao Ojima, Distinguished Professor in the Department of Chemistry and Director of the Institute of Chemical Biology and Drug Discovery at Stony Brook.

Refining potential drugs

Ojima’s group is synthesizing derivatives of the hits Pereira de Sa found and she will start tests outside a living organism, or in vitro, soon.

Ojima has synthesized several compounds using computer-assisted drug design. He is currently developing several inhibitors that scored high on his computational molecular docking analysis and will synthesize two to three dozen potential small molecules.

Ojima, who partnered with Pereira de Sa in this study, “greatly appreciates her and her seminal contributions to this project,” he wrote in an email. She made critical contributions to the study that ensured its success and Stony Brook is “very fortunate to have her as a leader in this project.”

Ojima plans to identify highly potent inhibitors individually for Aspergillus and Cryptococcus separately, and then will try to find and develop broad spectrum inhibitors based on those compounds.

The need for a treatment has increased dramatically as the number of immunocompromised patients has increased.

Invasive aspergillosis can have mortality rates above 90 percent. The World Health Organization last October released its first ever list of health threatening fungi, which includes Aspergillus.

Pereira de Sa suggested two possible uses for this inhibitor. It could work as a treatment, knocking down the virulence of the fungus or it could contribute to the development of a vaccine.

In strains with a mutated enzyme, a mouse model has full protection against infection.

Getting a vaccine approved through the Food and Drug Administration for immunocompromised individuals might be challenging, she said. Several studies would be needed to confirm its safety.

Del Poeta added that the vaccine his lab has developed is effective alone when heat killed, reducing the threat a live virus with a defective enzyme might pose to an immunocompromised patient. Del Poeta has been developing a vaccine for cryptococcus and aspergillus and is testing it for other fungal infections as well.

‘A beautiful cause’

Del Poeta described Pereira de Sa as a key contributor to his lab, who is methodical, systematic and hard working.

The program she is developing will take years to go to clinical trials, he added.

Del Poeta met Pereira de Sa in 2017, when he visited Brazil and spoke with her mentor, Daniel de Assis Santos, who gave her an enthusiastic reference.

After meeting with her for only five minutes, del Poeta offered her a job.

“I will never forget her face: surprised, joyful, excited and she could not hold back some tears,” del Poeta described.

Del Poeta is thrilled with his choice, as she has gone above and beyond his expectations.

Born and raised in Belo Horizonte, Brazil, Pereira de Sa lives in East Setauket with her husband Rodrigo Carvalho da Silva, who is an airplane mechanic.

She enjoys Long Island, particularly during the summer, when she goes hiking, visits parks, kayaks and goes paddle boarding.

Pereira de Sa is encouraged by the progress in her work and is hoping her research contributes to future treatments.

“We are developing tools to help people,” she said. “It’s a beautiful cause I’m fighting for.”

She said the mortality rate from these fungal infections is “very high,” especially because a fungus like Aspergillus is ubiquitous.

“The fungus is present everywhere,” she said. “We are inhaling the spores of it every day.”

The invasive fungal disease starts in the lungs and spreads to the rest of the body, including in the brain, which can cause seizures.

Pereira de Sa recognizes the urgency of developing an effective treatment.

“We need some solutions and we need it now,” she said. “We are not prepared to fight fungal infections” on a large scale.

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Victoria Greening at the Grotte Mandrin site in France. Photo by Svenya Drees

By Daniel Dunaief

Last summer, the Anthropology Department at Stony Brook University brought 13 students to the south of France to help gather information from a rich archaeological site called the Grotte Mandrin.

Asa Wong-Gómez at the Grotte Mandrin site in France. Photo by Nicholas Gonzalez

The trip with the Field School through SBU Study Abroad enabled the students to work in the field and gather information from a site that has provided a treasure trove of information about Neanderthals and Homo sapiens from 54,000 years ago.

The students found the trip successful, inspirational and, at times, exhausting.

“I did archeology all summer,” said Asa Wong-Gómez, a senior anthropology major at Stony Brook, who spent time in Kenya before joining the team in France. “It was really cool.”

Wong-Gómez recalled the thrill of finding teeth and stones in the dirt. “The first day, everyone’s first find was super exciting,” he said.

The field expedition, which was the first Stony Brook ran at this site, enabled students to forge connections with each other and with the site’s leaders, including Stony Brook Lecturer Jason Lewis, Ludovic Slimak, cultural anthropologist at the University of Toulouse-Jean Jaurès, and Laure Metz, an archaeologist at Aix-Marseille University.

Victoria Greening at the Zooarcheological Training and Research Laboratory. Photo by Nicholas Gonzalez

“Working with everyone so closely for that month definitely builds really strong connections that have lasted since,” said Victoria Greening, who graduated from Stony Brook in the winter and is planning to start a Master’s program in the fall at the University of Oxford.

She appreciated the opportunity to be a part of new discoveries.

“Working with something that’s not in the written records and discovering it yourself was a privileged feeling,” said Greening, who grew up in Yaphank.

A happy grown up

Echoing Gollum from the “Lord of the Rings” series, Slimak would look at something a student found and say, “my precious, this goes in a special bag,” Wong-Gómez recalled.

Slimak reflected the joy he took in discovering compelling finds. “It was amusing, watching a grown adult be so happy,” Wong-Gomez said.

Eva Marsh, who is a senior at Stony Brook in the anthropology department, appreciated the excitement of finding flint. A couple of students, she recalled, also found teeth, including a horse’s tooth. The group discovered a massive core, from which early Homo sapiens would chip off pieces to construct arrows they would shoot from a bow to bring down buffalo or horses.

On the first night gathering at their summer accommodations, Marsh said the group looked up at a star-filled sky.

“There was not a lot of pollution there” or other lights, which was “really amazing,” Marsh said.

Marsh was nervous on her first day, as she didn’t know what to expect. The team played games for the first few nights and discussed why they all signed up for the field experience. Each night at dinner, they discussed the events of the day, Marsh recalled.

Svenya Drees at the Grotte Mandrin site. Photo by Victoria Greening

For Svenya Drees, who grew up in Port Jefferson and is a Master’s Student in Lewis’s lab, the experience was familiar, as she had conducted field work during the summer of 2021. “I knew what to expect,” she said. Still, she found the discovery of pebbles from a distant river intriguing.

“There’s this whole mystery at the site about pebbles that made it into the assemblage,” Drees said. “These rocks were brought there from the local river. I thought that was pretty awesome.”

The theory about the pebbles is that Neanderthals or Homo sapiens, who had lived in the cave at different times, deployed the pebbles to help remove flakes from the rock cores these ancient ancestors used to create weapons.

Some challenges

While the students enjoyed the experience, with many of them planning to continue in their anthropological studies, the summer included some challenges.

The students stayed in a house at the top of a hill. At the same time, the cave was also on a hill. Each morning, they walked down the hill to a car that drove them to the bottom of the Grotte Mandrin site, where they walked about 15 minutes up to the field station. At the end of the day, they had to climb back up to their temporary home.

“After digging holes all day, walking up the hill was not my favorite part,” Wong-Gómez said. Greening suggested that future participants in the program, which will also run this summer, bring sturdy shoes.

The students also sometimes carried heavy containers filled with sand. The physical challenges notwithstanding, most of the students eagerly anticipate future such explorations.

“It’s definitely the right field for me,” said Greening. “Working at Mandrin solidified that for me.”

Wong-Gómez hopes to continue his field work at the University of Florida. The university has accepted him as a PhD student, although he is awaiting word on whether he gets funding.

“When I got the email that I was accepted, it didn’t feel real,” Wong-Gómez said. “I really want to do this.”

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A reconstruction by Ludovic Slimak of the arrows Homo sapiens likely used 54,000 years ago in France. Credit: Ludovic Slimak

By Daniel Dunaief

Have bow and arrow, will travel, even in Eurasia 54,000 years ago.

An archaeological site in the south of France that’s 70 miles from the coastline called Grotte Mandrin not only provided evidence that Homo sapiens and Neanderthals lived in this area around the same time, but also offered proof that early humans used bow and arrows to hunt for prey like bison and wild horses.

Jason Lewis. Photo from SBU

In research published in the journal Science Advances, Jason Lewis, a Lecturer in the Department of Anthropology at Stony Brook University; Ludovic Slimak, cultural anthropologist at the University of Toulouse-Jean Jaurès; and Laure Metz, an archaeologist at Aix-Marseille University, shared an extensive analysis of stone artifacts that demonstrated the use of bows and arrows.

These hunting tools, which inhabitants of the cave could use to pursue herd animals migrating between the Mediterranean region and the plains of Northern Europe, provide the earliest evidence of mechanically propelled projectile technology from Eurasia.

“We looked for diagnostic evidence of a very powerful impact once the stone tip hits something,” said Lewis. “We can see experimentally what type of damage” is produced on the tips of the arrows. The damage to these arrows is in line with everything that modern archers are doing because the tools human ancestors used were so light, Lewis added.

The collaborative effort to study these arrows in labs across two continents involved an extensive analysis of the flaking pattern around the tips of the arrows. The researchers didn’t find any of the organic materials that the early hunters would have used to create the bow.

This technology, which likely took about an hour to make, likely enabled Homo sapiens to bring down prey. Effective hunting from about 10 to 20 yards likely would have required more than one arrow, particularly with the size and strength of the targets.

At an archaeological site in the Middle East, scientists described stone tools around the same time that look similar to the bows and arrows humans in Eurasia used.

“The evolving modern humans were developing and using projectile technology,” Lewis said.  

Cultural differences

Lewis, Slimak and Metz showed in a seminal paper last year that Homo sapiens and Neanderthals had lived in the same cave, sometimes separated by a year or even a season.

While these two types of humans lived around the same time and in the same place, they didn’t share the same technology or have the type of cultural exchange that would enable Neanderthals, who typically hunted with hand-thrown spears, to use the same hunting tools.

“There’s no evidence of learning exchange,” Lewis said. Neanderthals did not start using the smaller points typical of the arrows or that would have been used as projectiles.

“It doesn’t look like there was a cultural exchange between the two groups,” Lewis said, as the artifacts from the time Neanderthals occupied the cave didn’t include any arrows.

Cultures sometimes develop identities that preclude using technology from other groups. Such cultural differences existed in the Maale and neighboring Tsamai people in Southwestern Ethiopia.

“Even though [bows and arrows] might be logically or objectively advantageous, some cultures suggest that ‘that’s not what we do,’” Lewis said.

Indeed, cultural differences have occurred in other areas that groups haven’t bridged, despite the availability of similar resources and the chance to learn the technology.

At the cave in Grotte Mandrin, researchers found a large collection of stone tools in Layer E of the cave.

The scientists believe the numerous arrows could have been the early equivalent of a munitions dump.

While bows and arrows would have provided a hunting advantage to Homo sapiens, the technology doesn’t explain why the two groups of early humans occupied the cave or dominated the area at different times.

“I doubt it comes down strictly to stone tool technology,” Lewis said. “There’s not a continuous march of occupation and expansion” as the interactions between the two populations were long lasting and complex.

Homo sapiens and Neanderthals moved up into a region and then moved back. This is akin to the way European settlers interacted with Native Americans when ships first crossed the Atlantic.

The Europeans moved into the region, interacted with people who already in the country, returned home, and then, at a later point crossed the ocean again.

Arrow studies

To understand the technology used to create these arrows, Metz and Slimak have spent years studying the way rocks flake off or get damaged in response to contact with animals or objects they hit when shot through the air.

Working for over a decade, Metz has been conducting experimental replication of the effect of use on these stone tools.

Scientists who shoot these stone arrows into carcasses from butcher shops can see the flaking pattern and scratches on the arrows.

Lewis explained that the flaking on the arrow heads could not have been made during the creation of the arrows themselves.

“Only high velocity strikes” could produce such markings, Lewis said.

These kinds of studies combine geology, physics and natural science. Lewis said John Shea, Anthropology Professor in the College of Arts and Sciences at Stony Brook University, has pioneered the study of such technology during the Pleistocene Ice Ages.

Lewis explained that his primary role is to bring the contextual understanding about how various types of early humans were using the landscape and interacting with the animals.

He also brings the context of work he does in Africa around the same time period as a comparator.

Lewis explained that more research would be forthcoming from this site.

“This is part of a larger modern human ability to conceptualize the world,” Lewis said. Early humans were trying to change their environment to match their needs, with boats, clothing, dwelling structures and other elements of their lives.

Such tool use could reduce hunting time and could enable a greater division of labor, suggesting that “each person didn’t have to do everything” to meet basic needs. 

 

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Turnersuchus hingleyae. Image by Júlia d’Oliveira

By Daniel Dunaief

Nature plays a slow game, drawn out over millions of years, of hide and seek. First, spectacular and elaborate creatures lived hunted, reproduced, and avoided predators millions of years ago. After they died in places like Dorset in the United Kingdom, their bodies became preserved in the muddy, shallow marine environment. The sediment was then covered over by rock layers and safely preserved.

Eric Wilberg in Coyote Buttes, Utah in 2018

Fast forward about 185 million years, after waves crashing upon the shore erode those rocks on a beach and expose those fossils.

Indeed, in 2017, in a UNESCO World Heritage site where scientists and fossil hunters and paleontologists like 19th century star Mary Anning made key discoveries, archeology enthusiasts Paul Turner and Lizzie Hingley found the head, backbone and limbs of a creature scientists had imagined, but hadn’t, until then, discovered.

Called a thalattosuchian, which is an ancient sister of modern day crocodile ancestors, this finding extended the timeline of when these coastal marine crocodiles lived.

In late 2019, Dr. Roger Benson, who was then at the University of Oxford, reached out to Pedro Godoy, a postdoctoral researcher at Stony Brook who Benson co-supervised during his PhD, and Eric Wilberg, Assistant Professor at the Department of Anatomical Sciences at Stony Brook University. The team, which included Alan Turner, Professor in the Department of Anatomical Sciences at the Renaissance School of Medicine at Stony Brook, planned to describe and characterize the fossil.

Benson said he had never met Wilberg before but had “read his work on croc evolution and really admired his systematic approach.”

This ancient crocodilian creature, which was about six feet long and was likely either a sub adult or an adult, is the first “thalattosuchian fossil complete enough to definitively identify as a member of the group of rocks older than about 180 million years ago,” Wilberg explained.

Wilberg, Godoy (who is now a postdoctoral researcher at the University of Sao Paolo), Turner and Benson (who is currently Macaulay Curator of Dinosaur Paleobiology at the American Museum of Natural History), recently published their study on this fossil in the Journal of Vertebrate Paleontology.

Godoy said that Wilberg is “an expert in this group of animals and it was great working with him on this.” Godoy added that this was an “important finding, which helps us fill a gap in the evolution of thalattosuchians.”

Benson suggested that this fossil provides a glimpse into the origin of thalattosuchians, indicating that the group originated before this fossil. The particular organism is the first discovered in a new species gathered by the two fossil hunters (see related story on right).

The Thalattosuchian group lived until the Early Cretaceous period, about 130 million years ago. These predators likely fed on fish or cephalopods like ancient octopi or squid.

Recently, another team of scientists discovered a thalattosuchian skull in Morocco, which is about five to 10 million years older than the Turnersuchus Wilberg described.

The discoveries “support our prediction that thalattosuchians evolved millions of years earlier —probably in the late Triassic” around 200 million or more years ago, Wilberg added. His analysis determined that the thalattosuchian lineage diverged from its last common ancestor with crocodile-relatives during the Triassic period.

Wilberg and other researchers will be on the lookout for additional specimens which can add details to the understanding of this species. This specimen was missing most of the front of the skull, all of the hindlimb and pelvis and most of the tail.

Specific features

By examining the spinal column and part of the forelimb, Wilberg explained that this species did not have forelimbs that evolved into flippers, like later descendants in the group. It would have been similar in overall body form to living crocodiles, which means that it likely had similar swimming capabilities. 

The specimen included a couple of partial teeth. Like all living crocodiles, it likely continually replaced its teeth throughout its life. Its bite force would have been less than a similar sized modern crocodile. The modern crocodylian skull evolved structural reinforcements to allow it to withstand the massive bite forces it generated.

Thalattosuchians skulls were “not as well reinforced, so they were probably not able to bite as hard,” Wilberg wrote. It seems likely that the “muscles that generate fast bites were large in this group, so they may have evolved for fast bites to capture small-moving prey.”

The Turnersuchus probably lived close to the coast in relatively shallow water. Like living crocodiles, it also likely spent time out of the water to bask in the sun (it was also cold blooded) and lay eggs. The climate of the region when this species lived would have been warmer than the current climate of the United Kingdom.

This creature was likely not an apex predator, with larger hunters like ichthyosaurs, pleiosaurs and probably sharks likely preying on it.

“We don’t have any direct evidence of predation from these groups on thalattosuchians, but it probably happened,” Wilberg added.

This particular fossil, like many other discoveries, has numerous unknowns. The gender of the individual (which scientists often determine by comparing body sizes) is unclear.

This particular find will “continue to be important moving forward in determining how thalattosuchians are related to other fossil crocodiles — every new species discovered is a chance to test existing hypotheses of how they are related to one another” which is important in determining how evolution occurred in the group, Wilberg explained.

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The fossil hunters who lent their names to an ancient crocodile

By Daniel Dunaief

The beaches along the southern shore of the United Kingdom have rich and ancient stories to share.

Lizzie Hingley and Paul Turner. Photo from Lizzie Hingley

Lizzie Hingley and Paul Turner — friends who met on the beach and started working together in 2016 — are eager to gather clues about the past. Fossil hunters at the UNESCO World Heritage Site in Charmouth in the United Kingdom, which is about a three-hour drive southwest from London, Hingley and Turner discovered fragments of an unusual fossil starting in 2017. “Initially, we just saw random bones,” explained Hingley, who finds, prepares and sells some of the fossils on her website. Some fragments appeared to be a jaw in the clay next to an initial stone block containing multiple bones.

Hingley, who lives a ten minute walk from a beach that is also referred to as the Jurassic Coast, said that it’s “very unusual to come across anything with lots of bones in it on the beaches.” She took the find to her workshop, where she used an air abrasive and pneumatic chisel. She noticed it was semi-articulated, which means the bones were arranged in something resembling a natural order.

It took about one and a half years for Hingley and Turner to collect all the pieces of this fossil. Turner found the first main block, Hingley discovered the jaw next to it, Turner uncovered the next two and she found the last piece.

“It was quite difficult to collect as it was coming out of a huge glacial landscape,” said Hingley.  It likely fell out of the cliff 50 years earlier and had been traveling to the front of the slip over the years. “This meant that, although we did try to dig for it, the best way to recover it was to wait for nature to uncover it for us,” she added.

Lizzie Hingley holding the ichthyosaur jaw she found when she was eight. Photo by Craig Chivers

Hingley and Turner visited daily to make sure they didn’t miss any pieces. The Charmouth Heritage Centre staff found a few loose vertebrae and reunited them with the rest of the fossil.

Hingley, who is one of about 15 people who regularly search parts of the seven miles of beaches almost daily, wanted to do more than collect this fossil — she wanted to know its history. Through her network, she found Roger Benson, who was a Professor of Paleobiology at the University of Oxford.

“It was great to work with him and see the scans being done,” she said. “He was instrumental” in bringing together a team of researchers who could analyze the finding and put it into historical context.

Indeed, Benson reached out to several researchers at Stony Brook University, including his former postdoctoral researcher Pedro Godoy, Assistant Professor Eric Wilberg and Professor Alan Turner (see related story on left) to gather information.

Close-up of ichthyosaur jaw. Photo by Lizzie Hingley

Their work concluded that this was a new species of marine crocodile. The ancient crocodile relative was named Turnersuchus hingleyae, after the fossil hunters who discovered it.

“It’s wonderful to have my name go down in history,” said Hingley, who also has a gastropod named after her.

Hingley, who is 35, started looking for fossils when she was six in Dorset, first on family holidays and then at every opportunity she could get. Over the years, she has found ichthyosaur skulls, ammonites measuring half a meter across, shark skin and teeth and numerous blocks containing hundreds of ammonites. When she was eight, she found a 20 centimeter ichthyosaur jaw, which is still part of her own collection.

Hingley is thrilled with her job, in which “every day is different and you never know what you are going to find or be working on,” she wrote. “I get to spend a lot of time in nature on the beach; the tide changes the beach every day, too.”

Benson described the beaches where Hingley and Turner search for new fossils as a European “pilgrimage for paleontologists.”

Hingley added that the process of erosion, which reveals fossils hidden in the cliffs along the beach, is something of a double edged sword, revealing fossils and threatening to carry them away.

A storm can decimate a beach and destroy fossils when the tide is too high to collect examples of creatures that lived as many as 185 million years ago. At the same time, erosion along the coast, caused by some of these same storms, reveals new fossils.

Walking along the beach, Hingley explained that it is almost incomprehensible to imagine the time scale separating her from the creatures who died so long ago.

The environment on the Jurassic Coast didn’t change much over those millennia.

“It is odd to think that you are collecting from the sea bed when it’s coming out of the cliff many meters above you,” she wrote. “The distance and time that these fossils have travelled to be found is incredible.”

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Christopher Gobler. Photo by Conor Harrigan

By Daniel Dunaief

When they can’t stand the heat, bay scallops can’t get out of the proverbial kitchen.

A key commercial shellfish with landings data putting them in the top five fisheries in New York, particularly in the Peconic Bay, bay scallops populations have declined precipitously during a combination of warmer waters and low oxygen.

In a study published in the journal Global Change Biology, Christopher Gobler, Stony Brook University Endowed Chair of Coastal Ecology and Conservation and Stephen Tomasetti, a former Stony Brook graduate student, along with several other researchers, showed through lab and field experiments as well as remote sensing and long-term monitoring data analysis how these environmental changes threaten the survival of bay scallops.

Stephen Tomasetti. Photo by Nancy L. Ford/ Hamilton College

Bay scallops are “quite sensitive to different stressors in the environment,” said Tomasetti, who completed his PhD last spring and is currently Visiting Assistant Professor of Environmental Studies at Hamilton College in Clinton, New York. Of the regional shellfish, bay scallops are the most sensitive to environmental stress.

Indeed, since 2019, bay scallops have declined by between 95 and 99 percent amid overall warming temperatures and extended heat waves. These declines have led to the declaration of a federal fishery disaster in the Empire State.

Tomasetti used satellite data to characterize daily summer temperatures from 2003 to 2020, which showed significant warming across most of the bay scallop range from New York to Cape Cod, Massachusetts. He monitored four sites with sensors in the water in addition to satellite data during a field deployment with scallops.

At the warmest site, which was in Flanders Bay, New York, the temperature was above the 90th percentile of its long term average during an eight-day period that overlapped with the scallop deployment. The bay scallops in Flanders Bay were “all dead by the end of the heat wave event,” Tomasetti said.

At the same time, low levels of oxygen hurt the bay scallops which, like numerous other shellfish, feed on phytoplankton. Oxygen levels are declining in some of these bays as nitrogen from fertilizers and septic systems enter these waterways. High nitrogen levels encourage the growth of algae. When the algae die, they decay, which uses up oxygen and releases carbon dioxide into the water.

Field and lab studies

In the field, Tomasetti measured the heartbeat of bay scallops in East Harbor, Massachusetts by putting optical infrared sensors on them that took heartbeat readings every 15 minutes for a month.

Stephen Tomasetti conducts field work in East Harbor during the summer of 2020.

When the average daily temperature increased, their average heart rate climbed, which the scientists used as a proxy for their respiration rate. A higher respiration rate meant that the scallop was expending energy more rapidly, potentially leading to reductions of energy reserves.

Additionally, Tomasetti measured how quickly the scallops fed on algae in the lab under warm temperatures and low oxygen.  These conditions caused the scallops to stop feeding or to feed slowly. Tomasetti interpreted this as a sign that they were waiting out the stress.

In the lab, bay scallops in the same conditions as the bays from Long Island to Massachusetts had the same reactions.

While a collection of fish and invertebrates feed on bay scallops, the effect of their die off on the food web wasn’t likely severe.

“I think there are other prey items that are likely redundant with scallops that cushion the impact,” Gobler explained in an email.

Solutions

Stephen Tomasetti with his wife Kate Rubenstein in East Harbor during the summer of 2020.

As for solutions, global warming, while an important effort for countries across the planet, requires coordination, cooperation and compliance to reduce greenhouse gases and lower the world’s carbon footprint.

On a more local and immediate scale, people on Long Island can help with the health of the local ecosystem and the shellfish population by reducing and controlling the chemicals that run off into local waters.

Waste management practices that limit nutrients are “super helpful,” Tomasetti said. “Supporting restoration (like the clam sanctuaries across Long Island that are increasing the filtration capacities of bays) is good.”

Gobler is encouraged by county, state and federal official responses to problems such as the decline in bay scallops, including the declaration of a federal disaster.

Long Island experience

A graduate student at Stony Brook for five years, Tomasetti was pleasantly surprised with the environment.

He had lived in New York City, where he taught high school biology for five years, before starting his PhD.

His perception was that Long Island was “a giant suburb” of New York. That perspective changed when he moved to Riverhead and enjoyed the pine forest, among other natural resources.

He and his wife Kate Rubenstein, whom he met while teaching, enjoyed sitting in their backyard and watching wild turkeys walking through their property, while deer grazed on their plant life.

Initially interested in literature at the University of Central Florida, Tomasetti took a biology course that was a prerequisite for another class he wanted to take. After completing these two biology classes, he changed his college and career plans.

Teaching high school brought him into contact with researchers, where he saw science in action and decided to contribute to the field.

At Hamilton College, Tomasetti has started teaching and is putting together his research plan, which will likely involve examining trends in water quality and temperature. He will move to the University of Maryland Eastern Shore in Princess Anne, MD this fall, where he will be an assistant professor in coastal environmental science.

As for his work with bay scallops and other shellfish on Long Island, Tomasetti looked at the dynamics of coastal systems and impacts of extreme events on economically important shellfish in the area.

Tomasetti is not just a scientist; he is also a consumer of shellfish.  His favorite is sea scallops, which he eats a host of ways, although he’s particularly fond of the pan seared option.

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CSHL Associate Professor Stephen Shea and Postdoc Yunyao Xie in Shea’s lab. Photo from CSHL/2020

By Daniel Dunaief

Good parenting, at least in mice, is its own reward.

No, mice don’t send their offspring to charter schools, drive them to endless soccer and band practices or provide encouragement during periods of extreme self doubt.

What these rodents do, however, protects their young from danger.

When a young mouse wanders, rolls or strays from the nest, it becomes distressed, calling out mostly to its mother, who is the more effective parent, to bring it back to safety.

Responding to these calls, the mother mouse carries the young back to the safety of the nest.

This behavior involves a reward system in a region of the mouse brain called the ventral tegmental area, or VTA. When the mouse effectively retrieves its young, the VTA releases the neurotransmitter dopamine, which is the brain’s way of saying “well done!”

In a paper published in December in the journal Neuron, Cold Spring Harbor Laboratory Associate Professor Stephen Shea and his postdoctoral researcher Yunyao Xie, who worked in the lab from 2019 to 2021, likened the release of dopamine in this area to a neurological reward for engaging in the kind of behavior that protects their young.

The research “proposes a mechanism that shapes behavior in accordance with that reward,” Shea said. The connection between dopamine in a reward system is an established paradigm.

“There was plenty of smoke there,” he said. “We didn’t pull this out of thin air.”

Indeed, in humans, mothers with postpartum depression have disrupted maternal mood, motivation and caregiving. PPD is linked to dysfunction of the mesolimbic dopamine system, which is a neural circuit that involves the VTA, Xie explained.

“Studies using functional magnetic resonance imaging (fMRI) revealed that the reward brain areas including VTA in healthy mothers have higher response to their own babies’ smiling faces than those in mothers with PPD,” Xie added.

What’s new in this research, however, is that it is “a study of how these signals use mechanisms to shape behavior and social interaction,” Shea said.

How the process works

The feedback loop between dopamine in the VTA and behavior involves a cumulative combination of dopamine interactions.

Dopamine is not at its highest level when the mouse mom is engaging in effective pup retrieval.

“Dopamine is shaping future, not current behavior,” Shea said. “If dopamine was driving the mouse on a current trial, a high dopamine level would be associated with high performance. The trial found the opposite: a low dopamine level was associated with high performance in a given trial, and vice versa.”

Like a skater laying her blades down effortlessly and gracefully across the ice after spending hours exerting energy practicing, the mother mouse engaged in the kind of reinforcement learning that required less dopamine to lead to effective pup saving behavior.

As the performance increases, dopamine diminishes over time, as the reward is “more expected,” reflecting a nuanced dynamic, Shea said.

To test the correlation between dopamine levels in the VTA and behavior, Shea and Xie created an enclosure with two chambers. They put a naive virgin female mouse, which they called surrogates, on one side and played specific sounds behind a door on each side of the chamber. The test mice initially had “no experience in maternal behaviors,” Xie explained.

As these surrogates became more experienced by either observing mothers or practicing on their own, the amplitude of the VTA dopamine signals got smaller.

To provide a control for this experiment, Xie monitored a group of naive virgin female mice who spent less time with pups and had to figure out how to retrieve them on their own under similar neurological monitoring conditions. The dopamine signals in this group stayed elevated over days and their performance in maternal behaviors remained poor.

Through these experiments, Xie and Shea concluded that “there is a negative correlation between the dopamine signals in the VTA and their performance in maternal behaviors,” explained Xie.

‘Mind blowing’ moment

In her experiments, Xie used optogenetic tools that allowed her to inhibit the activity of dopaminergic neurons in the VTA with high temporal precision.

Shea appreciated Xie’s hard work and dedication and suggested the discoveries represent a “lot of her creativity and innovation,” he said.

A native of China, Xie said her grandparents used to have a garden in which they taught her the names and morphologies of different plants during her childhood. She enjoyed drawing these plants.

In graduate school, she became more interested in neuroscience. She recalls how “mind-blowing” it was when she learned about the work by 1963 Nobel laureates Alan Hodgkin, Sir Andrew Fielding Huxley and John Eccles, who established a mathematical model to describe how action potentials in neurons are initiated and propagated.

In the study Xie did with Shea, she found that the dopamine signals in the VTA encoded reward prediction errors in maternal behaviors that was consistent with the mathematical model.

In the bigger picture, Xie is interested in how neural circuits shape behaviors. The neural circuits of most natural behaviors, such as defensive behaviors and maternal behaviors are hard-wired, she added.

Mice can also acquire those behaviors through learning. She is interested in how pup cues are perceived as rewards and subsequently facilitate learning maternal behavior. She found a great fit with Shea’s lab, which focuses on the neural mechanism of maternal behavior.

Xie enjoyed her time at Cold Spring Harbor Laboratory, where she could discuss science with colleagues by the bench, at the dining room or at one of the many on site seminars. She also appreciated the opportunity to attend neuroscience seminars with speakers from other schools, which helped expand her horizons and inspire ideas for research.

Next steps

As for the next steps, Shea said he believes there is considerable additional follow up research that could build on these findings. He would like to apply methods that measure the activity in individual neurons. Additionally, with a number of targets for dopamine, he wants to figure out what areas the neurotransmitter reaches and how the signals are used when they get there. More broadly, he suggested that the implications for this research extend to human diseases. 

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From left, Alea Mills and Xueqin Sun Photo from CSHL

By Daniel Dunaief

People have natural defenses against cancer. Proteins like P53 search for unwelcome and unhealthy developments. 

Sometimes, mutations in P53, which is known as the “guardian of the genome,” rob the protein of its tumor fighting ability. In more than seven out of ten cases, the brain tumor glioblastoma, which has a grim prognosis for people who develop it, has an intact P53 protein.

So what happened to P53 and why isn’t it performing its task?

That’s what Cold Spring Harbor Laboratory Professor and Cancer Center member Alea Mills and postdoctoral researcher Xueqin “Sherine” Sun wanted to know.

Starting with the idea that something epigenetic was somehow blocking P53, Sun conducted numerous detailed experiments with the gene editing tool CRISPR-Cas9.

She knocked out parts of the chromatin regulating machinery, which determines whether factors for DNA replication, gene expression, and the repair of DNA damage can access genes and perform their tasks.

The researchers wanted to find “something specific to glioblastoma,” Mills said in an interview. Working with a team of researchers in Mills’s lab, Sun focused on the protein BRD8.

In experiments with mice, Sun and her colleague inhibited this specific protein by destroying the gene that encodes it. That step was enough to stop the tumor from growing and allowed the mouse to live longer.

Mills and Sun published their work in the prestigious journal Nature just before the holidays.

The article generated considerable buzz in the scientific community, where it was in the 99th percentile among those published at the same time in attracting attention and downloads. It also attracted attention on social media platforms like Twitter and LinkedIn.

“We see this as a major discovery, and are not surprised that many others think that the impact is extraordinary,” Mills said. The paper “has the potential of having a significant impact in the future. The work is completely novel.”

While finding a connection between BRD8 and glioblastoma suggests a target for researchers to consider in their search for new glioblastoma treatments, a potential new approach for patients could be a long way off.

“We cannot predict how long it will take to be able to help patients” who have glioblastoma, Mills said.

A promising step

From left, Alea Mills and Xueqin Sun Photo from CSHL

Still, this finding provides a promising step by showing how knocking out the BRD8 protein can enable P53 to gain access to a life threatening tumor.

Sun and Mills said BRD8 and its partners lock down genes that are normally turned on by P53.

“What you inherit from mom and dad is one thing,” said Mills. “How it’s packaged, the epigenetic mechanism that keeps it wrapped up or open, is key in how it’s all carried out within your body.”

By targeting BRD8, Mills and her team opened the chromatin, so P53 could bind and turn on other cancer fighting genes.

After receiving patient samples from Northwell Health, Stanford and the Mayo Clinic, the team studied tissue samples from patients battling glioblastoma. Those patients, they found, had higher concentrations of BRD8 than people without brain cancer.

Researchers and, down the road, pharmaceutical companies and doctors, are careful to make sure removing or reducing the concentration of any protein doesn’t have so-called “off target effects,” which would interfere with normal, healthy processes in cells.

Mills said they tested such actions in the context of neural stem cells in the brain. At this point, removing BRD8 didn’t have any “deleterious consequence,” she said. 

Her lab is working to see the effect of reducing or removing the mouse version, also called Brd8, during development by engineering mice that lack this protein.

Future research

An important next step in this research involves searching for and developing viable inhibitors of the BRD8 protein.

For histone readers like BRD8, researchers look for an active domain within the protein. The goal is to interrupt the interface in their interactions with histones.

In creating molecules that can block the action of a protein, researchers often start with the structure of the protein or, more specifically, the active site.

Sun, who is currently applying for jobs to run her own lab after working at Cold Spring Harbor Laboratory for over eight years, is hoping to purify enough of the protein and determine its structure.

Sun is working on x-ray crystallography, in which she purifies the protein, crystallizes it and then uses x-rays to determine the atomic structure.

Sun described the search for the structure of the protein as an “important direction” in the research. “Once we solve the structure” researchers can focus on drug design, testing and other experiments.

She suggested that the search for a small molecule or compound that might prove effective in inhibiting BRD8 would involve optimizing efficiency and activity.

There is a “long way to go” in that search, Sun added.

She is working to generate a chemical compound in collaboration with other groups.

A long, productive journey

Born and raised in China, Sun has been an active and important contributor to Mills’s lab.

“I’ll miss [Sun] personally as well as in the lab,” Mills said. “She’s been a really good role model and teacher across the Cold Spring Harbor campus and in my lab.”

Mills is “really excited about [Sun’s] future,” she said. “She’ll be really great” at running her own lab.”

For her part, Sun enjoyed her time on Long Island, where she appreciated the natural environment and the supportive culture at Cold Spring Harbor Laboratory.

Sun described her time on Long Island as a “very exciting and satisfying journey.” 

She is determined to study and understand cancer for a number of reasons.

“I know people who died of cancer,” she said. “It’s a terrible disease and it’s urgent to find more efficient therapeutic strategies to stop cancers and improve human heath.”

Sun is also eager to embrace the opportunity to mentor and inspire other students of science.

“Teaching is very important,” she said. She looks forward to helping students grow as professionals to create the “next generation of scientists.”

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