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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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From left, Darren Martin and Benjamin Hsiao during a visit to Ram’s Head Inn on Shelter Island. Photo from Darren Martin

By Daniel Dunaief

One person’s garbage is another’s treasure.

Benjamin Hsiao

Benjamin Hsiao has plans to convert garbage — from dog poop to food waste and even cardboard boxes — into the kind of low cost materials and fertilizers that can help combat climate change. His primary target is agricultural residues because of their volume and collectability.  

A Distinguished Professor of Chemistry at Stony Brook University, Hsiao and collaborator Darren Martin at the University of Queensland in Australia recently were awarded one of 16 multidisciplinary grants totaling $11.4 million from the National Science Foundation’s Convergence Accelerator program.

Hsiao, who is the primary investigator, will receive $570,000 over the next nine months in Phase I of the research effort while Martin will collect $180,000 from the Commonwealth Scientific and Industrial Research Organisation in Australia.

The researchers plan to take a zero waste approach to create a circular system that will generate efficiencies, reduce pollution and combat climate change.

The research is focused on creating immediate solutions for current problems, Hsiao said.

The NSF received “many quality submissions” and chose the winners after a rigorous review process, the NSF said.

The proposal from Hsiao and Martin stood out as it is “based on strong science” and make a clear connection to climate change,” NSF officials said.

Hsiao and Martin were delighted with the award and the opportunity not only to make contributions through their own research, but also to work with some of the other recipients.

“I am so pleased on many counts,” Martin explained in an email from Australia. First, Martin and Hsiao, who met at a conference in 2014, followed through on long standing plans to work together. Second, this program, which the NSF started in 2019, is about “early engagement with the market to get feedback on new technologies and platforms.”

Martin suggested it was akin to a “business model boot camp” that includes support and opportunities to pressure test ideas early. “This approach could really accelerate and compress the number of years traditionally taken to see helpful new technologies out in society sooner.”

If they are successful and effective, the scientists can apply for competitive Phase II funding within the year, which includes $5 million for two years and which four or five of the Phase I recipients, who are from a host of A-list research institutions, will receive.

Solids and liquids

Hsiao has been working with solid plant-based waste to create filters that can purify water at a low cost since 2009.

“Nanoscale cellulose materials can be used for water purification,” said Hsiao.

The needles of plants, from shrubs to bushes to feedstock, all have the same cellulosic nanostructure. Hsiao’s technology can convert these different feedstock into similar carboxy-cellulose nanofibers that can be used as purifying agents with negative charge. These filters can remove oppositely charged impurities.

Additionally, Hsiao plans to use solid plant based biomass to create a biogel. Rich in nutrients, the biogel is like the naturally occurring residue that is at the bottom of streams, which is a nutrient-rich mix of dead trees and grass.

The biogel, which is also funded by the NSF, has three applications. First, it can replace soil to grow food or for seed germination, which could be useful to grow food in space. It can also reduce the impact of drought.

Second, it can make a farm more resistant to drought because the material in biogel retains water for a longer period of time and amid drier conditions.

Third, the biogel can induce vegetation or plant growth in drier or sandier areas. Such growth, which could occur along the shoreline of Long Island, could help reduce erosion, Hsiao said. The biogel can also reduce desertification.

Martin explained that Stony Brook University and the University of Queensland have two different biogel platforms that they may hybridize.

Hsiao’s team is “very strong in the chemistry and physical chemistry side,” Martin wrote. “Being based in a Chemical Engineering School, we have been pretty good over the years at finding the most efficient, cost-effective ways to manufacture bio-based materials and composites at scale.”

Fertilizer

Building and expanding on this work, Hsiao is focusing on the liquid waste from biomass as well.

“With the new thinking, we have a circular design,” he said.

Using a nitric acid treatment that is similar to composting and that removes human pathogens, liquid biomass can become an effective fertilizer, which sanitizes animal and human waste.

Nitric acid also releases the existing nutrients in feedstock, which provides more nitrogen and phosphorous to help plants grow.

The ideal treatment would involve providing a controlled amount of fertilizer each day, Hsiao explained.

Farmers, however, can’t put that kind of time and resources into spraying their fields. Instead, they spray a fertilizer that becomes run off when it rains. Artificial intelligence and robots can deploy fertilizer in a more cost effective manner.

The nitrogen from the run off winds up in streams and other water bodies, where it can cause a process called eutrophication, leading to the kind of algal blooms that rob oxygen of water, making it more difficult for desirable marine life to survive and close beaches to swimming.

By using an efficient process for producing fertilizer that includes taking the inedible parts of plants, and making them a part of the circular process, run off could decrease by “half or even more,” Hsiao said.

Martin added that he and Hsiao have, in the back of their minds, a plan to create scalable fertilizer for single family farms in developed and developing nations.

“Our modeling may indeed show that ‘distributed manufacturing’ of the biogels from agricultural residues using a ‘mobile factory placed on the farm’ may be the smartest way to get there,” Martin explained. “This is exactly the sort of question the Convergence Accelerator is designed to test.”

Martin said that he hopes this technology lead to an array of jobs that support farming under a variety of circumstances.

Sorghum, which is one of his favorite crops, is ultra resilient and is of increasing global importance. Its ability to withstand environmental stress and thrive on low input marginal farmland make it the ‘golden crop of the future,’ Martin added.

This crop makes it an “attractive option to transform infertile land into profitable agrivoltaic farms supplying raw materials for emerging non-foo markets such as these biogels,” Martin wrote.

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Kaushik Mitra. Photo from SBU

By Daniel Dunaief

From over 66 million miles away, they take pieces of a puzzle and try to fill in the picture. In addition to looking at what’s there now, they also use clues to look back in time.

For the last eight years, researchers suspected that the presence of manganese oxide suggested that Mars had atmospheric oxygen billions of years ago. That’s because, on Earth and in water, oxygen converts manganese to manganese oxide.

Such a process whets the appetite in the search for prehistoric life on Mars that, like so many creatures on Earth, breathed oxygen.

The Martian story, however, involves puzzle pieces that came together in a different way.

In a paper published last month in Nature Geosciences, Kaushik Mitra, a postdoctoral researcher at Stony Brook University in the Department of Geosciences, suggested through geochemical modeling that oxygen on Mars, even if it was abundant billions of years ago, wouldn’t have created manganese oxide.

That’s because the water on Mars was acidic, with a pH of less than 5.5, which is below the neutral 7 level. Under those conditions, oxygen wouldn’t oxidize manganese.

Using experiments, Mitra showed that the manganese oxide could form in acidic water in other ways.

“Mars and Earth fluid conditions are very different,” Mitra said. “What I showed in my experiments is that oxygen in acidic fluids will not be able to oxidize manganese.”

Mitra conducted research that were part of his PhD work in Jeffrey Catalano’s lab at Washington University in St. Louis, MO. 

Taking oxygen out of the picture, Mitra also detailed previous efforts that might explain the presence of manganese oxide, such as ultraviolet light. The manganese oxides formed in sub surface fractures, which this light couldn’t reach.

So, what happened?

“If the originally proposed (and plausible) oxidants were not the cause, there had to be some culprit,” Mitra explained in an email. “So there had to be some other oxidant.”

Bromine and chlorine

Enter chlorine and bromine, which are both halogens, or reactive non-metallic elements.

No one had looked into the potential of oxyhalogen compounds to produce manganese oxides in Mars-like conditions.

Bromate, which is a bromine atom attached to three oxygen atoms, can oxidize manganese in orders of magnitude faster than other oxidants, particularly in acidic conditions. Chlorate, which is also a chlorine atom attached to three oxygen atoms, alone can’t do it, but, with a small quantity of bromate, can create quantities of manganese oxide.

The oxygen attached to chlorine and bromine can come from water or any other ingredient, and doesn’t need oxygen gas to form.

“People didn’t really appreciate until [Mitra’s] paper came along that [manganese] is highly reactive towards these oxyhalogen compounds that he has been working with, so it gives us a whole new way to think about how [manganese-oxides] might form on Mars,” Joel Hurowitz, Associate Professor in Geosciences at Stony Brook University, explained in an email. Mitra has been working as a postdoctoral researcher in Hurowitz’s lab since November of 2021.

While oxygen may not have caused the change in manganese, the search for Martian life doesn’t end here. Some organisms, including on Earth, don’t need oxygen to survive.

Extremophiles, which can survive in the Great Salt Lake, the Dead Sea, and around hydrothermal vents at the bottom of the ocean, do not need oxygen.

Mitra’s research “teaches us to be cautious in our astrobiology strategy and consider all the alternative possibilities,” Hurowitz explained. “It is entirely possible that Martian life did not depend on [oxygen] or produce [oxygen] as a by-product of its metabolism.”

For the first two billion years of life on Earth, high concentrations of oxygen would have been toxic to microbial life, Hurowitz added.

To be sure, just because halogens like chlorine and bromine can explain the presence of manganese oxide instead of oxygen doesn’t rule out the possibility that Mars had oxygen.

Paradigm shift

Mitra has continued his exploration of the importance of oxyhalogen species in Hurowitz’s lab to improve the understanding of how they interact with various mineral phases that are considered key records of paleoenvironmental conditions on Mars.

On a more immediate scale, Mitra’s approach to his work has created something of a paradigm shift in Hurowtiz’s lab. When the postdoctoral researcher arrived at Stony Brook, he immediately started between 30 and 40 separate experiments within the span of a month. 

This effort contrasts with the attempt to create one perfect, completely controlled experiment that can take months of time that might be lost if something went wrong.

“It has actually changed the way that I think about experimental project methods,” Hurowitz wrote. “It’s a great new way to explore geochemistry and my students are adopting many of the approaches he’s brought into the lab.”

Hurowitz described Mitra as a “great addition” to the group.

A passion for science

A native of Bhagalpur, India, which is in the state of Bihar, Mitra had a strong interest in chemistry during his youth.

He attended the Indian Institute of Technology Kharagpur, where he earned an integrated Bachelors and Masters of Science Degree in Applied Geology.

Mitra, who currently lives in Centereach, is fluent in English, Hindi and Bengali and is learning Nepali, the native language of his spouse Priyanka Sharma who is from Nepal.

Sharma, who is an Indian Nepali, is applying for graduate school in English Literature and Comparative Literature.

An avid reader whose favorite genre is philosophy, Mitra is currently reading Fyodor Dostoesky and Friedrich Nietzsche.

A long distance runner, Mitra ran a 10K in Queens last year and would like to run a half marathon in the spring.

He will likely finish his postdoctoral research by next year, at the latest, at which point he will apply for a faculty job.

Passionate about teaching, Mitra has been a committed mentor to other students at Stony Brook, Hurowitz said.

Mitra created a YouTube channel for geology and geochemistry undergraduates and graduates in which he shares lessons about geoscience and chemistry in English and Hindi, which is available at https://www.youtube.com/@kmicalmindset6322.

“I am trying to inspire more people to come into planetary geoscience,” he said, especially undergraduates.

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Nandita Kumari at the 53rd Lunar and Planetary Science Conference in Woodlands, Texas in March of 2022. Photo by Delia Enriquez Draper from the Lunar and Planetary Institute

By Daniel Dunaief

Some day in the not too distant future, an astronaut may approach rocks on the moon and, with a handheld instrument, determine within minutes whether the rock might have value as a natural resource or as a source of historical information.

That’s the vision Nandita Kumari, a fourth-year graduate student in the Department of Geosciences in the College of Arts and Sciences at Stony Brook University, has.

In the meantime, Kumari was part of a multi-institutional team that recommended two landing sites in the moon’s south polar region for future Artemis missions. 

Nandita Kumari at a San Francisco Volcanic Field, where she was doing stress and strain measurements of cinders. Photo by Saurabh Subham.

The group, which included students from the University of Arizona, the University of California Los Angeles, and the University of Buffalo, used several criteria to recommend these two sites.

They looked at the resources that might be available, such as water and rocks, at how long the areas are in sunlight and at how the features of the land, from the slope of hills to the size of boulders, affects the sites accessibility.

“These two sites ended up fulfilling all these criteria,” Kumari said. Models suggest water might be present and the regions are in sunlight more than 80 percent of the time, which is critical for solar-powered devices.

The group used high-resolution data from the Lunar Reconnaissance Orbiter to create a map of all the rocks and to model the geological diversity of the site. They used infrared images to gather data from areas when they were dark. They also added temperature readings.

To the delight of the team, NASA selected both of the sites as part of a total of 13 potential landing locations.

Planetary scientist David Kring advised the group during the process. Kring has trained astronauts and worked on samples brought back from the Apollo missions.

At the end of the first year of her PhD, Kumari received encouragement to apply for the virtual internship with Kring from Stony Brook Geosciences Professor Tim Glotch, who runs the lab where she has conducted her PhD work.

Putting a number on it

Kumari said her thesis is about using machine learning to understand the composition of resources on the moon. She would like to use artificial intelligence to delve deeply into the wealth of data moon missions and observations have been collecting to use local geology as a future resource.

“Instead of saying something has a ‘little’ or a ‘lot’” of a particular type of rock that might have specific properties, she would like to put a specific numerical value on it.

An engineer by training, Kumari said she is a “very big fan of crunching numbers.”

Since joining the lab, Kumari has become “our go-to source for any type of statistical analysis me or one of my other students might want to conduct,” Glotch explained.

The work Kumari has done provides “large improvements over traditional spectroscopic analysis techniques,” Glotch added.

In examining rocks for silicic properties, meaning those that contain silicon, most scientists describe a rock as being less or more silicic, Kumari said.

“It’s difficult to know whether 60 percent is high or 90 percent is high,” she added. Such a range can make an important difference, and provides information about history, formation and thermal state of the planet and about potential resources.

With machine learning that trains on data collected in the lab, the model is deployed on orbiter data.

The machine learning doesn’t stop with silica. It can also be extended to search for helium 3 and other atoms.

Understanding and using the available natural resources reduces the need to send similar raw materials to the moon from Earth.

“There has to be a point where we stop” transporting materials to the moon, said Kumari. “It’s high time we use modern practices and methods so we can go through really large chunks of data with limited error.”

The machine learning starts with a set of inputs and outputs, along with an algorithm to explain the connection. As it sorts through data, it compares the outputs against what it expects. When the data doesn’t match the algorithm, it adjusts the algorithm and compares that to additional data, refining and improving the model’s accuracy.

A love for puzzles

Kumari, who grew up in Biharsharif, India, a small town in the northern state of Bihar, said this work appeals to her because she “loves puzzles that are difficult to solve.” She also tries to find solutions in the “fastest way possible.”

Kumari was recently part of a field exploration team in Utah that was processing data. The team brought back data and manually compared the measurements to the library to see what rocks they had.

She wrote an algorithm that provided the top five matches to the spectroscopic measurements the researchers found. Her work suggested the presence of minerals the field team didn’t anticipate. What’s more, the machine provided the analysis in five minutes.

The same kind of analysis can be used on site to study lunar rocks.

“When astronauts go to the moon, we shouldn’t require geology experts to be there to find the best rocks” she said. While having a geologist is the best-case scenario, that is not always possible. “Anyone with a code in their instruments should be able to decide whether it is what they’re looking for.”

As for her interest in space travel, Kumari isn’t interested in trekking to the moon or Mars.

While she believes the moon and Mars should be a base for scientific experiments, she doesn’t think people should focus on colonizing either place.

Such colonization ideas may reduce the importance of working on the challenges humans have created on Earth, including climate change.

“You can’t move to Mars,” Kumari said. The litmus test for that occurred during Covid, when people had to isolate.

“If we couldn’t stay in our homes with all the comfort and everything, I do not see a future where this would be possible with stringent constraints on Mars,” she added.

An advocate for women in STEM fields, Kumari said women should pursue scientific careers even if someone else focuses on their mistakes or tries to break their confidence.

“The only way to stop this from happening is to have women in higher places,” she explained. “We should also be supportive of each other and grow together.”

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Arianna Maffei, left, and lead author Hillary Schiff, in Maffei’s Neurobiology lab at Stony Brook. Photo by Josh F. Kogan

Findings from a Stony Brook University research team published in Science Advances

 Have you ever thought about how your food preferences came to be? Food preferences arise as a consequence of experience with food and shape eating habits and cultural identity, as Jean-Anthelme Brillat-Savarin nicely summarized in this quote from his work “The Physiology of Taste” published in 1825: “Tell me what you eat: I will tell you what you are.”

A new study by Stony Brook University researchers brought this concept to the scientific level and showed there is indeed a strong relationship between what we eat early in life, as babies or young children, and food preferences in adults. This relationship depends the effects of our early experience with food has on the brain. The research, published in Science Advances, highlights the importance of early exposure to a variety of tastes and identifies the neural basis regulating preferences for favorite foods, providing important new information about the relationship between nutrition and brain function.

Previous investigations of human infants hinted at the effect of early taste experience on food preference later in life. However, no previous study examined the neural bases of this phenomenon. This study looks at the neural bases of taste preference and provides findings that could form a basis to understanding the neural processes involved in taste preference.

The biology of the gustatory system is similar across all mammals. By using a murine model, the research team from the Department of Neurobiology and Behavior in the Renaissance School of Medicine exposed groups of mice to a variety of taste solutions for one week. They exposed groups as either weanlings (early exposure) or as adults (late exposure). After the one week experiencing a variety of tastes, they returned the groups to their regular diet, which is contains balanced nutrients but with is not rich in taste. For comparison, a control group of mice was raised only on the regular, blander diet.

“Our research is directed at assessing whether and how the gustatory experience and diet influence brain development. This study shows that the gustatory experience has fundamental effects on the brain. The next steps will be to determine how different diets such as a high fat, or a high sugar or high salt, may influence taste preferences and neural activity, ” explains Arianna Maffei, PhD, Senior Author and Professor in the Department of Neurobiology and Behavior.

Maffei, lead author Hillary Schiff, and colleagues increased taste variety in the healthy diets of mice and found that the development of neural circuits and taste preference are influenced by all aspects of the gustatory experience: sensations in the mouth, smell, and gut-brain relations.

Several weeks after exposing the groups to the one-week taste variety, the investigators measured preference for a sweet solution compared to water. Mice who experienced taste variety early in life had a stronger preference for sweet tastes in adulthood compared to the control group. This change preference depended on a combination of taste, smell, and gut-to-brain signals, and was specific to early exposure taste. Mice exposed to taste variety as adults did not show different sweet preferences from their age-matched control group. These results indicated that taste experience influences preference, but only if given within a restricted time window.

The researchers also recorded the activity of neurons in the gustatory cortex of all the subjects. This part of the brain is involved in taste perception and decisions about ingesting or rejecting foods. The recorded activity showed that the shift in sweet preference was associated with differences in the activity of inhibitory neurons of adult mice.

This led to the question of whether manipulating these inhibitory neurons in adulthood can re-open the window of sensitivity to the taste experience.

To answer this question the research team injected a substance into the gustatory cortex that breaks down perineuronal nets, which are webs of proteins that accumulate around inhibitory neurons early in life. Once established, these nets play a key role in limiting plasticity – the ability to change in response to stimuli at inhibitory synapses.

When adult mice without perineuronal nets in the gustatory cortex were exposed to the taste variety, they showed a similar change in sweet preference as the group exposed earlier in life. This manipulation “rejuvenated” inhibitory synapses in the gustatory cortex and restored plasticity in response to taste experience, which confirmed the importance of maturation and plasticity in inhibitory circuits for the development of taste preference in the experimental model.

“It was striking to discover how long-lasting the effects of early experience with taste were in the young groups,” says Schiff. “The presence of a ‘critical period’ of the life cycle for the development of taste preference was a unique and exciting discovery. The prevailing view from other studies prior to this finding was that taste does not have a defined window of heightened sensitivity to experience like other sensory systems such as vision, hearing, and touch.”

The authors maintain that while the study was done in mice, the results inform scientists on the fundamental biological aspects of experiences with taste that extends beyond animal models and to humans.

“The development of taste preference requires a full gustatory experience,” adds Maffei. “This includes the detection of taste in the mouth, its association with smell and the activation of gastrointestinal sensations. All these aspects influence the activity of brain circuits, promoting their healthy development.”

Regarding humans, Maffei points out that we often favor food from our childhood, highlighting important cultural aspects of our taste experience. Additionally, in the public health realm several neurodevelopmental and neurodegenerative disorders are often associated with hyper- or hyposensitivity to gustatory stimuli, suggesting links between taste and brain function in health and disease .

“Expanding our knowledge of the developmental neural circuits for tastes – as studies like this do – will contribute to our understanding of food choices, eating disorders, and diseases associated with brain disorders,” emphasizes Maffei.

Schiff, Maffei, and collaborators conclude that their overall experimental results establish a fundamental link between the gustatory experience, sweet preference, inhibitory plasticity, circuit function, and the importance of early life nutrition in setting taste preferences.

The research was supported by several grants from the National Institute on Deafness and Other Communication Disorders and from the National Institute of Neurological Disorders and Stroke at the National Institutes of Health.

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The Brown Mouse Lemur (Microcebus rufus) is recognized as a vulnerable species on Madagascar. Photo by Chien C. Lee

A new study by a team of international scientists including Liliana M. Dávalos, PhD, of Stony Brook University’s Department of Ecology and Evolution, reveals that it would take three million years to recover the number of species that went extinct from human activity on Madagascar. Published in Nature Communications, the study also projects that if currently threatened species go extinct on Madagascar, recovering them would take more than 20 million years – much longer than what has previously been found on any other island archipelago in the world.

From unique baobab species to lemurs, the island of Madagascar is one of the world’s most important biodiversity hotspots. Approximately 90 percent of its species of plants and animals are found nowhere else. After humans settled on the island about 2,500 years ago, Madagascar experienced many extinctions, including giant lemurs, elephant birds and dwarf hippos.

Yet unlike most islands, Madagascar’s fauna is still relatively intact. Over two hundred species of mammals still survive on the island, including unique species such as the fossa and the ring-tailed lemur. Alarmingly, over half of these species are threatened with extinction, primarily from habitat transformation for agriculture. How much has human activity perturbed Madagascar away from its past state, and what is at stake if environmental change continues?

The team of biologists and paleontologists from Europe, Madagascar and the United States set out to answer this question by building an unprecedented new dataset describing the evolutionary relationships of all species of mammals that were present on Madagascar at the time that humans colonized the island.

As a co-author of “The macroevolutionary impact of recent and imminent mammal extinctions on Madagascar,” Daválos helped design the study, interpret a previously published lemur phylogeny, and analyzed prospects for new species discovery in Madagascar.

The dataset includes species that have already gone extinct and are only known from fossils, as well as all living species of Malagasy mammals. The researchers identified 249 species in total, 30 of which already are extinct. Over 120 of the 219 species of mammals that remain on the island today are currently classified as threatened with extinction by the IUCN Red List, due to habitat destruction, climate change and hunting.

Using a computer simulation model based on island biogeography theory, the team, led by Nathan Michielsen and Luis Valente from the University of Groningen (Netherlands) and Naturalis Biodiversity Center (Netherlands) found that it would take approximately three million years to regain the number of mammal species that were lost from Madagascar in the time since humans arrived.

The research team also determined through the computer simulation that if currently threatened species go extinct, it would take much longer: about 23 million years of evolution would be needed to recover the same number of species. Just in the last decade, this figure has increased by several million years, as human impact on the island continues to grow.

The amount of  time it would take to recover this mammalian diversity surprised the international team of scientists.

“These staggering results highlight the importance of effective conservation efforts in Madagascar. Here at Stony Brook, we can have an extraordinary impact on preventing extinction because of the longstanding biological field research at Centre ValBio and the associated Ranomafana National Park, with ongoing research on conservation while enhancing local livelihoods,” said Dávalos.

“It was already known that Madagascar was a hotspot of biodiversity, but this new research puts into context just how valuable this diversity is,” says leading researcher Luis Valente, Assistant Professor at the University of Groningen. “The time it would take to recover this diversity is much longer than what previous studies have found on other islands, such as New Zealand or in the Caribbean.”

The study findings ultimately suggest that an extinction wave with deep evolutionary impact is imminent on Madagascar, unless immediate conservation actions are taken. The good news – the computer simulation model shows that with adequate conservation action, we may still preserve over 20 million years of unique evolutionary history on the island.

 

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Stony Brook Professor John Fleagle during a paleontology expedition in Ethiopia. Photo by John Shea

His work in the evolution of primate locomotion and adaptation spans 50 years

 John Fleagle, PhD, Distinguished Professor of Anatomical Sciences at Stony Brook University’s Renaissance School of Medicine, has won the Charles Darwin Lifetime Achievement Award. Granted by the American Association of Biological Anthropology (AABA), the award will be presented at the association’s annual conference held April 19-22 in Nevada. Known as the AABA’s most prestigious honor, this yearly award recognizes a senior member of the association who has exhibited a lifetime of contributions and commitment to biological anthropology.

Fleagle is only the second Stony Brook professor to receive the Charles Darwin Lifetime Achievement Award. In 2004, it was bestowed upon the late Robert R. Sokal, Distinguished Professor Emeritus of Ecology and Evolution.

Professor Fleagle’s presence in the field of biological anthropology spans half a century. Much of his work has centered around investigating primate evolution, primate locomotion, and broad patterns of evolution and adaptation across many taxa. From Argentina to India, his fieldwork has taken him across the world. In Ethiopia, Professor Fleagle directed a groundbreaking study that uncovered fresh insights into the African origin of homo sapiens.

Professor Fleagle has mentored and trained young anthropologists, founded and edited an authoritative review journal called Evolutionary Anthropology, and authored a highly regarded textbook titled Primate Adaptation and Evolution. He is also a member of the Scientific Executive Committee of the LSB Leakey Foundation.

“I’m delighted that John was granted the award,” said AABA President Steven Leigh. “His work is remarkable and has made major impacts across many aspects of our discipline. His textbook set the standard for our field and I consider it one of the best textbooks in any field.

“Personally, John helped me immensely 30 years ago when I was a postdoc at Stony Brook just getting a start in the field,” added Leigh. “It will be a career highlight for me to present the award to him.”

Professor Fleagle is a MacArthur Fellow, a Guggenheim Fellow, and a member of three graduate programs at Stony Brook University – the Doctoral Program in Ecology and Evolution, the Interdepartmental Doctoral Program in Anthropological Sciences, and the program in Anatomical Sciences.

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CSHL’s David Spector (center) and postdoctoral fellows Rasmani Hazra on left and Gayan Balasooriya on right. Photo courtesy of CSHL

By Daniel Dunaief

One came from India, the other from Sri Lanka. After they each earned their PhD’s, they arrived on Long Island within seven months of each other about seven years ago, joining a lab dedicated to studying and understanding cancer. Each of them, working on separate projects, made discoveries that may aid in the battle against heart disease.

Working for principal investigator David Spector at Cold Spring Harbor Laboratory, postdoctoral fellow Rasmani Hazra, who grew up in Burdwan, India, found a link between a gene that affects cancer in mice that also can lead to a problem with the development of heart valves.

Hazra worked with two long noncoding RNAs that are highly expressed in mouse embryonic stem cells, which have the ability to differentiate into many different types of cells.

Specifically, she found that mice that didn’t have Platr4 developed heart-related problems, particularly with their valves.

At the same time, postdoctoral fellow Gayan Balasooriya, who was born and raised in Sri Lanka, discovered that a single, non-sex gene is governed by different epigenetic mechanisms based on whether the gene is inherited from the mom or the dad.

While it was known that males are more susceptible to heart disease than females, researchers did not know which copy of the gene related to those diseases are expressed. This discovery could help in understanding the development of heart defects.

“Although we ended up at heart development” in both of these published studies, “we didn’t initiate” looking for heart-related information, said Spector. “The science led us there.

Spector, however, expects that the lessons learned about differentiation in the context of the developing heart can also “impact out knowledge about tumors” which he hopes will eventually lead to advances in how to treat them.

He added that any clinical benefit from this work would take additional research and time.

An on and off switch

In Hazra’s study, which was published in the journal Developmental Cell, she worked with Platr4 because humans have several possible orthologous genes. 

When Platr4 expression, which shuts down after birth, is deleted from cells or embryos, the mice died from heart valve problems.

The human equivalent of Platr4 is located on chromosome 4. At this point, clinical case studies have connected the deletion of this chromosome to cardiac defects in humans.

Hazra said her project initially examined the function of these long non-coding sections of RNA. She was exploring how they affected differentiation. She found this link through in vitro studies and then confirmed the connection in live mice.

Spector explained that this work involved extensive collaborations with other researchers at Cold Spring Harbor Laboratory, including teaming up with researchers who can do electrocardiograms on mice and who can assess blood flow.

A shared mouse imaging resource also helped advance this research.

“One of the advantages of Cold Spring Harbor Laboratory is that we have over 10 shared resources, each of which specializes in sophisticated technologies that scientists can use on their own projects,” he said. Each lab doesn’t have to learn and develop its own version of these skills.

Hazra plans to continue to study other long noncoding RNA. She is also working on glioblastoma, which is a form of brain cancer.

Hazra plans to start her own lab next fall, when she completes her postdoctoral research.

Inactive gene

Balasooriya, meanwhile, published his research in the journal Nature Communications.

He used RNA sequencing to identify numerous genes. He also looked at whether the RNAs originated from the mom or dad’s genes in individual cells.

Also planning to start his own lab next fall, Balasooriya found changes that alter gene expression between the alleles from the mother and the father experimentally and through data mining approaches.

“What was most surprising in my studies is that [he identified] the gene from the father’s side and the mother’s side are regulated in a different manner,” Balasooriya said. “I’m interested in following up on that finding.”

The next step for him is to look not only at the heart, but, more broadly, at how monoallelic gene expression changes the way regulators affect development and disease.

“I want to do a deep dive to find out the mechanisms” involved in this expression of a single copy of the gene, Balasooriya said, which could provide ways to understand how to control the process.

In the long run, this kind of research could provide insights into ways to treat heart disease as well as other diseases like cancer and immune diseases.

Growing up in the North Western Province in Sri Lanka, Balasooriya was interested in math and science. After he finished his bachelor’s degree in biology in Sri Lanka, he earned a master’s in molecular biology at the University of Hertfordshire in England. He “got so excited about biology and exploring new fields” that he decided to pursue his PhD at the University of Cambridge, England.

After college, he worked in computer science for a while and realized he was not passionate about it, which encouraged him to do his master’s. The experience in computer science helped him with bioinformatics.

As for Spector, he is pleased with the work of both of his postdoctoral researchers. “This is what being a principal investigator is all about, having young people join your lab, sitting down with them, discussing a potential project, not really knowing where it’s going to go,” he said.

He described both members of his team as “extremely successful” who were able to make discoveries that they shared in prestigious journals. Balasooriya and Hazra both laid the groundwork to go and start their own careers. 

“Seeing the fruits of their work is the most rewarding experience” as the leader of a lab, Spector said.

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Isabella Rossellini ‘s new one woman show Darwin’s Smile reconciles two worlds that are often at the opposite ends: art and science. Photo by © André Rau/CSHL

By Daniel Dunaief

A model and actress, Isabella Rossellini has spent her life as a part of numerous stories. Nowadays, the 70-year old Rossellini, who has a home in Bellport, is eager to share the next chapter in her story-telling.

This time, Rossellini will bring her one-woman show “Darwin’s Smile,” which she originally wrote in French but will perform in English, to Cold Spring Harbor Laboratory’s Grace Auditorium for a two-day run on Saturday and Sunday, March 4 and 5, 2023.

Tapping into her love for animals, Rossellini plans to share her observations and insights about the nexus between her art as an actress and the science she studied and observed when she earned her Master’s Degree from Hunter College in animal behavior and conservation.

“What I would like to do is share my wonderment and stupor about information I learned” about animals, Rossellini said in a recent interview with Times Beacon Record News Media. “Science is notoriously difficult. The language is very enigmatic. Even to read Darwin is complicated. Once you get it, it’s really incredible.”

Indeed, Rossellini wrote the show as an extension of  the 1872 book by Charles Darwin titled Expression of the Emotions in Man and Animals, which was published 13 years after his famous On the Origin of Species.

Darwin studied a range of expressions from people all over the world and discovered that some of those expressions, such as smiling, responding to fear, or being disgusted, are the same regardless of the cultural background.

Darwin, Rossellini said, believed that evolution through natural selection shaped these expressions of emotion, the same way natural selection might affect a bone, the horns on a buck or the shape of a bird’s beak. The core of emotion across species appeals to her as an actress and as someone who appreciates and admires animals.

“Modeling is all about expression,” said Rossellini, who was the world’s highest paid model in 1982. “Yes, you have to be beautiful, and all this. What makes a good model is not so much beauty. People respond to emotion, rather than a beautiful nose or a beautiful mouth.”

As she did with her series of shorts called “Green Porno,” in which Rossellini dressed as creatures such as a praying mantis, shrimp, snails, spiders, and whales, among others, and described their mating, Rossellini uses humor to entertain and educate in “Darwin’s Smile.”

At one point, she dresses as a peacock with an attractive tail. Darwin, Rossellini said, found the brilliant colors of those feathers overwhelming, which gave him a headache.

Rossellini emerges from her peacock costume in another costume and sings a song, slowly, in French.

In her show, Rossellini uses her acting skills to convey emotions that use the same words. Repeating “I love you and I want to be with you all my life,” she shares that thought with rage, love and sadness, making it clear through her acting that humans derive meaning from a range of cues.

On a scientific level, Rossellini would like to challenge the idea that research into animals can’t include a recognition of their emotions. The science of behaviorism suggested that researchers shouldn’t “project any emotion into animals,” she said. Many scientists look, instead, directly at the behavior of animals.

“Darwin did not have that problem,” she said. He recognized that his dog was happy to see him and that a cat was angry.

As for the emotions she feels when she views her own acting performances, Rossellini suggested her experience mirrors that of many other actors and actresses. “It’s difficult to see oneself on screen in front of everybody,” she said. The mental image she has of herself sometimes conflicts with what she sees on screen.

“It’s very disturbing,” she said. “I don’t really like to watch my past work.”

The movies also create some melancholy for her, as they can evoke memories of her experiences during filming. She said the film “Blue Velvet” conjures thoughts of the time she and the cast, with whom she shared close friendships, worked together in Wilmington, North Carolina.

Sometimes she watches her movies twice. The first time, she adjusts to herself on screen. The second time, she follows the storyline and plot.

In terms of movies that came out this year, Rossellini said the film EO, which is about the life of a donkey who performs in a circus and then moves from one challenging circumstance to another, “makes you feel for the farm animal.” She described the film, which was made in Poland by director Jerzy Skolimowski, as “kind of beautiful.”

As for her life, Rossellini, who is the daughter of famed director Roberto Rossellini and actress Ingrid Bergman, said her interest in animals started when she was around 14 and her father gave her the book King Solomon’s Ring by Konrad Lorenz.  

When she read the book, she thought “this is what I want to be,” Rossellini said. Only later, after modeling and acting, both of which she continues to do, did she add ethology to the mix. 

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Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor will host a special performance of “Darwin’s Smile” at Grace Auditorium on March 4, with doors opening at 5 p.m. The show starts at 6 p.m., followed by a reception and Q&A with Rossellini led by Helen Hou, an assistant professor and neuroscientist at CSHL. 

An encore performance (sans Q&A and reception) will be held March 5, with doors opening at 3 p.m. and showtime at 4 p.m. For tickets, visit www.cshl.edu. For further information, call 516-367-8800.

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From left, Patricia Wright with Pamela Reed Sanchez, President and CEO of the Seneca Park Zoo Society with the Warrior Award, a depiction of a tree growing out of rock, designed and created by artists at the Corning Museum of Glass. Photo courtesy of Amanda Lindley

By Daniel Dunaief

For only a short period of time, Patricia Wright was just a primatologist who studies the charming lemurs of Madagascar.

Now the Herrnstein Professor of Conservation Biology and Distinguished Service Professor at Stony Brook University, Wright first trekked to the island nation off the southwest coast of the African continent in 1986 to understand and study these unique primates.

Within a year, she realized she wouldn’t have much to observe and understand in a perilously short time if she didn’t also work to protect them, their habitat, and many other threatened and endangered animals and plants.

With the help of the government of Madagascar, Wright created a protected area known as Ranomafana National Park, which includes 41,500 hectares of space, keeping loggers, poachers and others from threatening to eradicate animals and plants that are unique to the country.

Between the original effort to create the national park and today, Wright has collected numerous honors and distinctions. She has won three Medals of Honor from the Malagasy government and become the first female recipient of the coveted Indianapolis Zoo Prize in 2014.

Recently, the Seneca Park Zoo in Rochester, New York named Wright its inaugural “Conservation Warrior,” providing her with a $20,000 prize in recognition for conservation work that has had a lasting, meaningful impact on species survival.

Patricia Wright with her Warrior Award from the Seneca Park Zoo.

“Dr. Wright’s early years were spent in Rochester, New York and it is fitting that the inaugural Conservation Warrior award be bestowed upon arguably the most influential conservationist to come out of the Finger Lakes region,” Pamela Reed Sanchez, President and CEO of the Seneca Park Zoo Society, explained in an email.

The newly anointed conservation warrior recently traveled to Montreal as a member of the Madagascar delegation at the fifteenth meeting of the Conference of the Parties to the Convention on Biological Diversity, or COP-15.

While she’s in Montreal, she plans to meet with conservation donors in an all-out effort to save wildlife on Madagascar, where almost all the reptiles and amphibians, half of its birds and all of its lemurs are only found on the island nation.

Wright hopes to raise $250 million for the country and $50 million for Centre ValBio (CVB), the research station she created in Ranomafana in 2003 and that employs 80 Malagasy staff. CVB has developed a conservation network around CVB that includes work with 75 villages.

Drew Fellman, who directed and wrote the Island of Lemurs documentary, encouraged donors to support Wright’s efforts. Wright and CVB are at the “front line of defense and anyone who cares [about] wildlife and endangered species should lend them a hand,” Fellman wrote in an email. He described how some species of lemurs are down to fewer than 10 individuals and “without conservation, there will be nothing left to research.”

In areas where conservation isn’t a priority, the region has lost habitat and biodiversity. In the northern areas of Madagascar, loggers and timber exporters reduced rainforest areas to grasslands, she said.

In the bigger picture, Wright said Madagascar needs funding immediately as the country is “closer to the brink of extinction with so many more species.” Saving plants and animals in Madagascar extends beyond committing to the protection and stewardship of vulnerable creatures. It also could provide benefits for people.

“So many lemur species are close relatives [to humans] and contain genetic information” about Alzheimer’s, diabetes and other conditions, she said. Additionally, creatures like bamboo lemurs regularly eat large quantities of cyanide, which would kill humans. Understanding how they can tolerate such high quantities of cyanide could provide an antidote.

The forests in the national park, which might otherwise attract loggers, prevent erosion, silting and landslides, she explained.

The benefit of a research stations like CVB extend beyond gathering information and conducting experiments.

In a recent correspondence in Nature Communications, lead author Timothy Eppley, a postdoctoral fellow at San Diego Zoo Wildlife Alliance along with three other scientists including Wright, argues that field research stations “are on the front line of biodiversity conservation, acting as no-take zones that rewild surrounding ecosystems.”

In the correspondence, Eppley and his colleagues said that these stations are “invisible” in global environmental policy, despite their importance in conservation.

“Our point in the paper is that this has not been given any conservation attention,” said Wright. “Nobody is funding us for doing conservation” even though these sites are “conservation engines. We should be given recognition and more conservation money.”

Eppley, who leads SDZWA’s lemur conservation program, added that the Nature correspondence didn’t include any of the data the group collected.

While Eppley cautioned in an email sent from Madagascar that it’s difficult to generalize about conservation efforts at field stations, he said many have some conservation initiatives or projects, or that some element of their research includes a strong conservation component.

“Without the conservation piece, all other research will eventually disappear: we need the ecosystem and animals to exist in the first place,” he explained.

Eppley suggested that scientists often approach conservation initiatives that they can test on a small scale and then, if they are effective, find the best way of scaling up those initiatives for entire protected areas, landscapes, countries or broader geographic regions.

As for the honor Wright received from the Seneca Park Zoo, Eppley believes such recognition dovetails with their recent correspondence piece in Nature Communications.

Wright “founded CVB and has been tirelessly building it into a globally recognized field research station,” he wrote.

Bringing international recognition to the work being done at CVB “highlights the overall importance of field research stations and why they need to be included in global environmental policy frameworks,” Eppley added.

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