Power of 3

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Gordon Taylor with Tatiana Zaliznyak, Taylor’s technician who also runs the facility, standing in front of the rest of the microspectrometer. Photo by John Griffin, SBU

It’s enough to make Dr. Seuss’ Horton the Elephant and the Whos — those brave little folks we would not want to lose — proud.

Gordon Taylor, a professor of Oceanography at Stony Brook University’s School of Marine and Atmospheric Sciences, is taking a spectacularly close look at the micro community of organisms that live, eat, process elements like nitrogen, carbon, oxygen and sulfur, in droplets of ocean water.

In a milliliter of water, there are about a million bacteria, ten million viruses and about 10,000 protozoa, Taylor said. “Their cosmos is pretty much in a droplet of water.” Small though they may be, however, they are “ubiquitous,” with the ocean harboring millions of species or microorganisms.

Taylor is studying something he calls the “marine microbial community” whose composition, activity and ecosystem services vary in space and time. Understanding these communities can help oceanographers get a better grasp on the way these network of creatures affect ocean health, climate, pollution and disease in marine life.

Taylor is exploring the microbial food web in which prey items are creatures like bacteria and single-celled algae and predators are single-celled organisms that are the cousins of paramecium, amoeba and euglena.

These creatures also live with the “proverbial monkey wrench of viruses, which are also a part of this microbial food web. Every known form of life has at least one type of virus that has co-evolved to attack it,” Taylor suggested. Many organisms have multiple viral pathogens that challenge their health. On average, viruses outnumber bacteria by a factor of 10.

Colleagues at Stony Brook suggested that an appreciation for these microbial communities has broader implications.

Above, Gordon Taylor with a confocal Raman microspectrometer. Photo by John Griffin, SBU
Above, Gordon Taylor with a confocal Raman microspectrometer. Photo by John Griffin, SBU

“Understanding how microorganisms catalyze the cycling of nutrients and their responses to environmental change provides information for predictive models which are useful for informing future policy and management decisions,” explained Josephine Aller, a professor in the SoMAS. “Sometimes this information can help to alter conditions which have caused change and reverse ecological damage.”

The development of technology that can account for and interpret life at these smaller scales has enabled scientists of all kinds to ask a range of new questions about increasingly small parts of life. Physicists, for example, long ago went well past exploring protons, electrons and neutrons, and are studying quarks, gluons and other subatomic particles.

To study the marine microenvironment, Taylor will use confocal Raman microspectrometry and atomic force microscopy at the NAno-RAMAN Molecular Imaging Laboratory. A National Science Foundation Major Research Instrumentation program grant and matching support from Stony Brook helped establish the lab.

In Raman spectroscopy, researchers shine a laser light through a lens onto the specimen. This technology is used to grade commercial diamonds. When the laser light, which is a single wavelength, hits the specimen, most of the photons are absorbed or scattered at the same wavelength. In about one in a million cases, however, the light loses energy to a molecular bond, with potentially covalently bound elements of all sorts causing Raman scattered photons. The spectra produced are a fingerprint of molecular bonds.

Taylor has coupled this spectroscopic instrument with an atomic force microscope, which can look at the surface topography and structure of small creatures. “I believe that we are the only marine/atmospheric/environmental science program in the U.S. with such a system,” he said.

Even with the technology, the two and three dimensional imaging of what’s happening remains a significant challenge, Taylor said. To explore this, he will flash-freeze seawater containing microbial communities, organic particles, gels and minerals to examine spatial relationships of organisms and processes from as close to their perspective as possible, he said.

He will also conduct tracer experiments where he adds heavy isotopes of elements like carbon and monitors how organisms react. Taylor will start by proving that he can see the organisms and the way the miniature ecosystem works.

The late Carl Sagan, narrator and co-writer of the TV series “Cosmos: A Personal Voyage,” “wondered at the cosmos,” Taylor said. “We are enthralled by the microcosmos.”

Once Taylor can define the ecosystem, he can explore how changes in temperature, pH and other environmental conditions affect life in the water droplets.

He said the structure within this small community is like a spider web. Protein strands and gels give structure to the water. Biologists are becoming increasingly interested in the ecology of small creatures that interact in these spaces, creating micro-communities that, when multiplied exponentially across the ocean, affect the global climate and its ability to react to changes in carbon dioxide or increases in temperature.

Taylor lives in East Setauket with his wife Janice, their Rhodesian ridgeback dog Luca who is five and weighs 111 pounds, and an eight-pound Boston Terrier named Iggy Pup. The Taylors’ daughter Olivia lives in lower Manhattan and will start a master of fine arts program in the fall.

As for his work, Taylor said understanding small scales in biology is critically important. “We can’t fully understand epidemiology within populations, human diseases, immune responses or therapies without comprehending processes at the molecular level,” he said.

Or, as Dr. Seuss might say, a microorganism is an organism, no matter how small.

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Brian K. Lebowitz photo by Jeanne Neville, Stony Brook Medicine

What, exactly, do test results mean? It is a question professionals in teaching, human resource and medicine grapple with routinely. A lower SAT score, for example, could reflect anything from a poor night’s sleep the night before, to a cold test room, to a lack of familiarity with the type and style of questions asked.

Similarly, doctors and researchers routinely use tests. Sometimes, the tests can show something specific, like a bone fracture or a break. Other times, however, the tests can leave room for interpretation, particularly if those tests involve processes that go on in a complex area, such as the mind.

Brian K. Lebowitz, director of neuropsychology training and clinical assistant professor of neurology at Stony Brook University, recently showed that a cognitive test might incorrectly suggest signs of the type of problems associated with Alzheimer’s disease.

“It’s possible that people are mislabeled because if [they] have a lifelong cognitive weakness, they [might] perform poorly” on the test, Lebowitz said.

Generally, people who have memory problems, or so-called mild cognitive impairment, visit Lebowitz or other neuropsychologists to understand if they are developing age-related problems or a chronic challenge, like Alzheimer’s disease.

Previous conditions or difficulty learning, however, may complicate a diagnosis in interpreting scores on any cognitive evaluations.

“If you had difficulty with cognitive processes that led to reading disorders in childhood, in forming complex language at age eight,” you might have it at age 80, Lebowitz suggested. “Our study, as well as clinical experiences, suggests that this is the case.” This, he continued, “is exactly what we would like to know.”

Lebowitz recently published his analysis in the Journal of Alzheimer’s Disease.

“Some of the results on all different kinds of tests” can arise from different challenges because “different cognitive skill sets overlap,” said Thomas Preston, the director of Neuropsychology Service at Stony Brook. Lebowitz’s article on mild cognitive impairment can help those who work with patients gain a better understanding of a patient’s history “prior to any perceived decline.”

Lebowitz looked more closely at the possible connection between test scores and reading challenges after speaking extensively with adults who had performed poorly on reading tests.

“Often during the interview, a patient will indicate that they have always struggled with reading or that they were diagnosed with dyslexia,” Lebowitz said. “Based on the reported histories, it was clear that at least for some patients, cognitive test scores reflected longstanding difficulties.”

In more recent times, child psychologists and education professionals have focused on dyslexia and other reading difficulties. Around 50 years ago, assessing learning disorders was not part of the American educational system, said Lebowitz. “People may have been called slow learners or readers. If you were to ask an older adult if he had dyslexia, he’d have no idea,” he added.

Stony Brook’s neuropsychological assessment team sees a wide range of patients with difficulties that include dementia, stroke, people with vehicular brain injuries, cancer, tumors and numerous other challenges. They also see people with epilepsy and learning disabilities. Their patients range in age from pediatric to geriatric.

Lebowitz often provides information about why some people feel as though they are unable to succeed professionally or socially. With an older adult, he takes into account their life story, as well as their likely lifelong pattern of cognitive strengths and weaknesses, when interpreting test results, he said.

In addition to his research results and a good rapport with his patients, Lebowitz has helped reduce the evaluation time needed for adults, Preston said.

“He has a thorough but efficient method of evaluating” patients, Preston said. “Dr. Lebowitz has brought a new type of efficiency.” At one point, the typical neuropsychological evaluation could take as long as eight hours. That can now take two and a half hours, Preston said.

Lebowitz has been at Stony Brook for eight years and lives in Poquott with his 13-year-old Labrador retriever Japhy, whom he adopted as a rescue dog during his fellowship. For recreation, he enjoys taking a scuba diving trip each year. After returning from a trip to the Galapagos Islands in December he said, “every dive in the Galapagos was the best dive I’ve ever done.”

As for his recent research article, Lebowitz recognizes that there’s still considerable work to do to understand how to connect tests with diagnoses and treatment, particularly for mild cognitive impairment that might suggest Alzheimer’s.

“The challenge for all health care professionals who work with older adults is to identify cognitive decline at the earliest possible point,” he said. “As treatment options become available, identifying and treating patients before symptoms progress will be even more important.”

At this point, Lebowitz said he doesn’t know if he’s identified people who are being mislabeled as mild cognitive impairment because he has yet to follow them over time. People with a lifelong weakness “may be vulnerable to brain changes later in life.”

Still, these results highlight why it’s important for medical professionals to take into account a complete history in developing a diagnosis, instead of relying on a score on a particular test, he said.

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Above, algae growing in plastic grids in Ian Blaby’s lab. Photo from Blaby

This is the second of a two-part series on Brookhaven National Laboratory’s Crysten and Ian Blaby.

While his wife is something of a metal worker, Ian Blaby is much more of a farmer. He cultivates rows upon rows of an unusual crop under numerous different conditions to see how they’ll grow and respond.

Like his wife Crysten Blaby, the organism he studies is a single-celled algae, which means those rows upon rows of crops can fit on the top of a bench, instead of dotting an expansive green field in the middle of the country.

Ian Blaby, who was born in Torquay, England, and earned his Ph.D. at Cambridge University, wants to know what genes are involved in carbon metabolism as the power algal couple look to unlock some important genetic secrets. The algae they study, Chlamydomonas reinhardtii, has 17,741 genes.

“We have a good idea what 5 to 10 percent of those genes are doing when it comes to the functioning of the cell,” Blaby said. Scientists have a vague idea for about another 40 percent, which means that about half of those genes are unknown. His goal is to figure out how the products of those genes, proteins, interact with each other.

Understanding these genes can translate into a better awareness of similar genes in more complex and diverse organisms, such as food and biofuel crops, Blaby said. The overlap and the potential for unlocking important genetic codes for more complex plants has led the Department of Energy to designate the alga a flagship species.

“It has been recognized as having a lot of potential,” Blaby said. He estimates there are about 100 labs around the world that are studying it.

John Shanklin, the head of the plant sciences group at BNL, likened the understanding of the genes of the algae to seeing the skyline of a city from a distance. While the view might provide information about where the buildings are, it doesn’t reveal much about what’s inside them. The information Ian and Crysten Blaby collect can provide greater insights about the genetic inner workings of this algae.

Additionally, Shanklin said medical researchers have been able to take studies done with yeast and apply them to human diseases. The similarities between algae and plants are two- to fourfold higher than they are between yeast and humans.

Discovering gene functions is “one of the, if not the, biggest problems in biology,” Blaby said. “Many, many labs around the world are tasked with addressing this. My approaches are not unique, but certainly very specialized.”

Indeed, using plastic grids that allow individual conditions in 384 small squares, Blaby can see how the alga grow and survive under a host of conditions, all at the same time. Blaby uses hundreds of these plates in any one experiment. He compares different strains under the same conditions of light, temperature or composition of the growth medium, or compares the same strains under different conditions.

Screening all those small squares would be laborious work and would invite human error.

“By the time we might be looking at plate 177, human error could creep in,” Blaby said. Instead, he uses robots to transfer the plates from incubators to readers. He gets real time information on how every strain is behaving under each condition.

When Blaby finds a plate where the growth is conspicuously different from the parent alga, he can go back and screen for the genetic differences. This can help him focus in on a particular genetic sequence.

“A different behavior can be assigned to a gene, or region of DNA, providing clues to a specific function which can then be followed up using other methods,” Blaby explained. This would be considerably harder and more difficult with crop plants that have more genes and a considerably longer time to produce the next generation.

Crop plants present numerous complications, including the time to grow, the space requirements, and the challenge of growing them under carefully controlled conditions, in addition to the different genes for roots and leaves, expressed in different cells.

For the algae, the doubling time is about eight hours, which means that this algae can be handled in a lab in a way that’s similar to bacteria.

Blaby’s interest in carbon metabolism stems from his post-doctoral work in Los Angeles.

“Carbon forms the basis of biofuel,” he said. He hopes to identify “novel genes that are involved in fuel production but that weren’t known.”

While scientists like Crysten and Ian Blaby are studying single-celled algae in their lab, they have the big picture goal of the application and translation of their work to a real-world problem and limitation that will affect future generations of people.

“We’re making more people, but we don’t have more land area for growing crops,” Shanklin said. “The only options are to grow crops” on currently unused land or to “make the growth more efficient. We’re working on both sides.”

The BNL department has a mandate, along with other researchers working with the DOE, to “make plants more efficient. We can’t do that if we don’t know what the genetic parts are of the plants” that are important for survival in different conditions, Shanklin added.

In addition to hiring Ian and Crysten Blaby and Qun Liu this fall, BNL is in the process of working with the DOE on long-term planning. “We’re looking at how big this program can become,” Shanklin said. He is excited about the work Ian and Crysten Blaby are doing. “It’s not enough to work hard,” he said. “You have to identify big problems and work on those. The problems they are addressing are ones that are holding back whole elements of science.”

Shanklin sees Ian and Crysten Blaby as contributing more together than the sum of their research parts. “They are both independently excellent scientists who have different but complementary skill sets,” he added.

This version corrects the name of the type of algae Ian Blaby is studying and the town in England where he is from.

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Crysten and Ian Blaby. Photo by Kevin Keck

Part 1 of a two-part series.

She is a “creative thinker,” while he is a “fearless experimentalist,” according to UCLA Distinguished Professor Sabeeha Merchant. Brookhaven National Laboratory recently hired the tandem of Crysten and Ian Blaby in the Biology Department.

Crysten and Ian Blaby did their postdoctoral work in Merchant’s lab for about five years. Merchant believes “there is no question that they will make discoveries to advance knowledge.”

The Times Beacon Record Newspapers will profile the scientific studies of the Blabys. This week’s column will highlight the work of Crysten Blaby, and next week’s will profile Ian Blaby.

Crysten Blaby is something of a metal worker, although she doesn’t dig anything out of the earth, wear a hard hat or ship metals by the ton. In fact, the amount of metal in her job is so small that the copper, iron, zinc and manganese she works with in a year wouldn’t fill a teaspoon.

That’s because Blaby (pronounced like “baby” with an extra letter) studies a one-celled algae called Chlamydomonas reinhardtii. This organism survives in a wide range of environments, where the amount of available metals can be precariously low, dangerously high, or can bounce back and forth between extremes.

Blaby, who is an assistant biologist at BNL, would like to know which proteins in these algae, among other species, including bacteria, plants and animals, are involved in maintaining a balance of metals.

“I am focused on the genes and proteins in metal homeostasis,” she said. That means she wants to know what genes are active in different environments.

Understanding the molecular biology of algae can provide clues about where to look for similar genes in more complex members of the plant kingdom. Discovering these processes could help farmers develop techniques that will foster growth for biofuel crops that are cultivated on lands that are less suited for food production.

“With this research, we could find easy, cheap ways to ‘diagnose’ whether crops are deficient in metal nutrients and best know how to remedy it,” she explained. “This research could also be used to help select which crops or breeds would thrive best given the quality of a particular soil.”

While Blaby won’t help produce new biofuel crops, her discoveries about the genes involved in metal homeostasis is part of “foundational science” that will underpin those types of discoveries, said John Shanklin, the head of plant science research at BNL. “Without [Ian and Crysten Blaby] doing this” the scientists who want to produce biofuel crops in inhospitable environments “are stuck.”

Blaby’s work could also help provide information that might translate into therapies for human conditions.

Menkes disease and Wilson’s disease are two inherited disorders of copper metabolism, which are caused by dysfunctional copper transporters, she said.

Blaby recently discovered a copper chaperone that looks similar to a molecule in humans and that’s involved in keeping algae safe from accumulations of copper. She suggested that the chaperone in algae protects the cell from copper by making sure that it is hand delivered between proteins. More research, however, is needed to ensure this model is accurate.

Blaby is studying the biochemical routes these metals take into the cell. The main gatekeepers controlling the movement of metal ions across membranes are likely transporters, she said.

Blaby is scheduled for beamline time at the new National Synchrotron Light Source II facility at BNL this April. The process of getting time on the beamline is extremely competitive, with numerous top-notch scientific projects rejected in part because the facility can’t yet meet the demand for a light source that is 10,000 times more powerful than the original synchrotron.

“People recognize [Crysten and Ian Blaby] are asking cutting-edge questions and they are trying to assist them in every way they can,” Shanklin said. “Everyone wants to be a part of [their] success.” After she moved to BNL, Blaby developed her NSLS-II application with Professor Emeritus Keith Jones, a physicist who she said is involved in experiments at the new synchrotron, and several of his collaborators.

“The goal is to uncover where metals travel in the cell after uptake and before they are loaded into target proteins, and understand which proteins, such as transporters, are involved” in this process, she said.

Blaby is collaborating with Qun Liu, another new hire at BNL, to look at transporter proteins, to understand how many different kinds there are, and “figure out how plants move nutrients around,” Shanklin said.

One of the ways she can solve how genes respond to different environments is by using small RNAs to knock down gene expression.

Ian and Crysten, who met when they worked in a lab in Florida, are residents of Miller Place. When they met, they were “instantly friends,” she said, in part because of their shared interest in science. They each appreciate having someone who “understands the challenges, disappointments and pure joy of discovery that comes with pursuing this career.”

The plant biologists have a two-year old daughter Emily.

As for their work, Crysten Blaby said they collaborate with each other but also concentrate on those areas where they have each developed their individual skills.

“We focus on the pathways for genes that are involved in processes that we have expertise in and where our passion lies,” she said.

This version corrects the department Crysten and Ian Blaby work in at Brookhaven National Laboratory.

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Rainbow over NSLS-II: Brookhaven National Laboratory’s National Synchrotron Light Source II is a state-of-the-art 3-GeV electron storage ring. Photo from BNL

They built something that makes Superman’s x-ray vision seem antiquated by comparison. Many of them have dedicated as much as a decade of their lives to constructing a cutting-edge technology that will help researchers around the world see small, rapid processes as they are happening.

As 2016 begins, scientists from around the world are heading to Brookhaven National Laboratory in Upton to look closely at processes and atomic configurations at the National Synchrotron Light Source II, a $912 million scientific facility completed last year. At the same time, those involved in constructing this project plan to continue to add beamlines.

The project originally came in under budget and ahead of schedule, allowing BNL to expand the size of the ring building, which improves the performance from the instruments, among other enhancements.

“In principal, at least in a peripheral way, if it involves analysis of the structure and function of materials, there is nothing beyond the reach of a facility like NSLS-II,” said Erik Johnson, who has held a variety of positions at NSLS-II from accelerator interface manager to finishing as the deputy project director.

“This is not only an increase in quantity but on quality” of information,” said Ferdinand Willeke, who came to BNL in 2007 as the head of the Accelerator Division, which built and operates the magnet storage ring. “In an extreme case, data are collected 10,000 times faster.” Willeke said the process involved a seven-layer structure with about 30,000 activities.

“The project was more a marathon than a sprint, but, as in each large project, there are issues to resolve to keep everything proceeding smoothly,” Willeke said. “This required enormous commitment from the entire staff” who routinely went the extra mile “from the start to the end.”

Those who worked on the project credited a large team of people for helping to complete the NSLS-II. That includes Steven Dierker, who was the project director, Marty Fallier, who was the Facilities Division director during the design and construction, Diane Hatton, who was the business manager, and John Hill, Qun Shen and Paul Zschack, who were, at various times, in charge of the beamlines. Satoshi Ozaki served as senior project advisor. Samuel Krinsky “was a prominent accelerator scientist who had a large influence on NSLS-II accelerator layout in the pre-project phase,” Willeke said. Krinsky passed away last year.

The project itself included hundreds of workers in various stages, while leaders from different groups routinely met in person or sent emails back and forth during weekends, vacations or personal time, ensuring that the process stayed on target and under budget. “I’ve invested 10 or 15 years of my life to bring this to reality,” said Johnson.

So far, the reviews from the beamlines that have gone live have been encouraging. “The performance of the accelerator itself is a dream,” said Elaine DiMasi, a physicist in the Photon Sciences Division at BNL. “According to all reports, its stability and brightness are every bit as good as what was theoretically planned.”

As a facility funded by the Department of Energy, the NSLS-II can uncover undocumented details about batteries while they are in use. Indeed, scientists can place batteries in front of the beamline and determine exactly what happens as they discharge, potentially leading to a more effective design of future batteries and energy storage devices.

“Imagine all the material things you could do with the capabilities we have here, in trying to improve energy efficiency or energy conversion,” Johnson said. “In my view, next to food security, [energy security] is at the top of the geopolitical issues that shape the world.”

Johnson is interested in seeing what the NSLS-II can reveal about catalytic reactions and chemical pathways. In some biochemical reactions, catalysts help speed up or direct processes. Along the way, however, some intermediate steps are far preferable to others, which might slow a reaction.

“When you have a chemical reaction, you may want this [molecule or intermediate step] and not the other six,” Johnson said. The NSLS-II will allow scientists to focus on what they can do to the catalyst to encourage one particular step. “You may wind up making configuration changes to the way the molecules are absorbed on the working catalyst surface so some chemical pathways are more favored than others. There’s a whole gamut you can look at now that you couldn’t [see] before.”

While the team who made the NSLS-II a reality is pleased with what it can do, they realize there’s still considerable work ahead. “We are still in the process of bringing this machine to full performance,” said Willeke.

DiMasi said those who are building the second, third and fourth waves of beamlines are “sprinting to complete our tasks and help make the full build-out a reality.”

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Jessica Tollkuhn. Photo from the lab of Michael G. Rosenfeld

Mickey Mouse, if he were a real mouse, would engage in typical male behavior: He’d be aggressive toward other males, he’d look for a mate, presumably Minnie, and he’d mark his territory.

Jessica Tollkuhn, an assistant professor at Cold Spring Harbor Laboratory, would like to uncover how and when signals from hormones trigger a series of genetic steps that lead to characteristic sex-specific behaviors. A molecular biologist by training, Tollkuhn joined CSHL last September.

Ultimately, understanding these steps may help with treatments for human conditions that have different outcomes, depending on the sex of the individual. “There are a lot of sex differences in mental health disorders,” Tollkuhn said. “Autism, ADHD and dyslexia are all more common in men and boys while mood disorders are more common in girls and women.”

While the steps from exploring sex differences in mice to extrapolations to humans are large, the types of experiments Tollkuhn conducts can provide a potential window into the molecular pathways that lead to these mental health challenges.

Tollkuhn’s studies exploring differences in the development of the male and female brain may “give us insights into how these circuits are different,” said Stephen Shea, an associate professor at Cold Spring Harbor Laboratory. Her work could “bring us closer to treatment” and to “understanding” the causes of the disparity in these mental health diseases between the sexes.

Shea is interested in species typical natural behaviors, including sexual behaviors in mice, he said. He studies those from a behavioral and circuit perspective, while Tollkuhn works on tools to understand how those are regulated at the genetic level. He said that has created “a natural collaboration for us.”

Tollkuhn works with neuroscientists at CSHL to connect behavior and development with the genetic steps that lead to those behaviors. She provides “a bridge between areas,” Shea said. “She has a multidisciplinary aspect that fits well with Cold Spring Harbor Laboratory, which unites people and draws links between separate areas.”

For Tollkuhn, mice present a model system that allows her to explore key moments in development. Researchers have shown that exposure to testosterone at birth, which is gone within 24 hours, leads to male mouse behaviors later in life.

Mice are born with almost all their neurons. The wiring occurs during their first two weeks of life, she said.

In the brain, an enzyme called aromatase turns that hormone into estrogen. The bump in the hormones in the brain “are necessary and sufficient to masculinize brain development,” in mice and other rodents, Tollkuhn said. “You can see changes in gene expression, in brain wiring patterns, and in behaviors” all from that narrow window of time.

Indeed, female mice that have estrogen in their brains during this critical early period become masculinized and will fight with other males when they get older. “Transient events in development have long-lasting effects on the brain and behavior,” Tollkuhn said. The cells in the brain that respond to the presence of hormone during development are located in the hypothalamus and the amygdala.

Tollkuhn said her long-standing interest is in understanding how genes define cell identity and function. In the brain, exploring how cells lead to behavior is a challenging question because scientists are just beginning to understand what each cell type does and how they are connected.

The sex differences are a model system Tollkuhn uses to understand the relationship between genes and behavior. She is studying how genes are turned on and off during development. The sex-specific behaviors of mice present opportunities to explore innate behaviors that don’t have to be trained.

In her work, Tollkuhn is profiling gene expression — looking at what genes are on or off — and chromatin — a combination of DNA and protein — in the brain. She’s doing this specifically in the neurons that have the receptor for estrogen.

Tollkuhn “has tools to assess chromatin,” Shea said. Tollkuhn has been “canny in developing or incorporating new techniques for sequencing DNA and understanding chromatin structure and she’s positioned herself at the forefront of those technologies.” Her greatest strength, he continued, is that she’s “put the pieces of these two worlds — the neuroscience of sex in the brain with these cutting edge techniques” together.

A resident of Huntington, Tollkuhn and her husband Joe Mulvaney, who writes software for scientists, have two sons. Franklin is four and a half and Linus is one.

Tollkuhn said she appreciates the family friendly environment at CSHL. “It’s nice to be somewhere where it’s not just okay, but it’s a positive to have family around at the lab and campus,” she said. She described her colleagues in the community at Cold Spring Harbor Laboratory as “fantastic.”

As for her work, Tollkuhn said she hopes to find new molecular targets for therapies and medications to treat mental health diseases.

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Michael Bell casts a minnow trap at Loberg Lake in Palmer, Alaska. Photo by Peter J. Park

The creation of a freeway in Los Angeles put Michael Bell on the road to his career choice. When Bell was about 12 years old, construction near his home cut through rocks that contained a treasure for him: fossil fish.

“I formed a relationship with the Natural History Museum in LA County and started bringing fossils [to them],” Bell recalled. “I had friends who would do it for a week or two and then they’d had enough. I did it endlessly. In a way, that’s how my career started.”

Michael Bell casts a minnow trap at Loberg Lake in Palmer, Alaska. Photo by Peter J. Park
Michael Bell casts a minnow trap at Loberg Lake in Palmer, Alaska. Photo by Peter J. Park

Indeed, that career led him to Stony Brook University, where he arrived in 1978 and is a professor in the Department of Ecology and Evolution. Bell was co-editor of “The Evolutionary Biology of the Threespine Stickleback” in 1994 with Susan A. Foster.

Recently, the American Association for the Advancement of Science elected Bell as a Ffellow. Bell said he appreciated the “broader recognition of his work.”

Those who have collaborated with him said Bell is a leader and an exceptional scientist.

Bell’s “contribution to the field has been enormous,” explained Windsor Aguirre, a former graduate student who is an assistant professor in the Department of Biological Sciences at DePaul University who still works with Bell. “Many of the most important papers in the field have been made possible or greatly enhanced [by Bell’s efforts],” he said.

From those early days, Bell has focused on the threespine stickleback, a fish that used to be considerably more prevalent at Flax Pond in Old Field and in the Great South Bay.

This particular fish, whose three sharp spines on the top of its body prevent some predators from swallowing it, appeals to scientists for a host of reasons —  from the variation it exhibits within and among populations to its relatively small size and ease of maintaining in a lab.

Bell has focused on establishing the relationship between traits and environmental factors. These fish can live in the sea ­— where they contend with the usual saltwater dilemma, where the concentration of salt is higher than in body fluids — and in freshwater, where salt is lower than in their body fluids.

Like salmon, they breed in brackish water (water that’s in between fresh and salty) and freshwater. The population of fish that evolve in freshwater can continue to survive despite having marine ancestors.

Indeed, the evolution, through mutations, of these fish is so rapid that they defy Charles Darwin. Coming up with the theory of natural selection when he studied the many unique birds in the Galapagos Islands 600 miles off the coast of Ecuador, Darwin believed that evolution occurred on an almost imperceptibly slow time scale.

“Darwin underestimated the potential for rapid evolution,” Bell said. “He believed evolution is slow.” Sticklebacks have traits that evolve at high rates.

Bell has studied stickleback fossils in Nevada and California and modern stickleback in California and Alaska.

He has often studied the armor plates of stickleback, which have a marine and a freshwater version. In the ocean, the freshwater version would theoretically occur only once in about 10,000 young sticklebacks, because it’s a disadvantage to that individual. However, in a different environment, the fish with the freshwater armor plating becomes the natural selection superstar.

In an experiment in Cheney Lake in Anchorage, Alaska, Bell released sea-run stickleback. A year later, none of the fish had the freshwater plates, while fewer than 1 percent had them two years later. Six years after the experiment began, however, one in five fish had these plates.

“When you put the fish in freshwater, it evolves,” he said.

A resident of Stony Brook, Bell chose to live close enough to the university to walk to work. That, he said, was by design because he moved in during the gas crisis in the 1970s and didn’t want to wait in line for gas or struggle to get to work.

Bell and his wife Cynthia Blair travel to farms out east, shop and visit vineyards. Bell enjoys wandering through stores, especially for craft objects, which Blair also likes and makes herself. She designed a pillow of Bell, surrounded by swimming sticklebacks.

After four decades of research, Bell remains as inspired to find fossils and gather evidence about these rapidly evolving and adaptive fish as he was when he was a teenager.

“I won’t ever really retire,” said Bell, although he does expect to cut back so that he can travel with his wife. He appreciates being able to visit the shore of a lake in Alaska and “see what comes up in traps. It’s all still fun — making samples of modern and fossil stickleback, getting results that mean something scientifically and standing in front of a class and explaining biology to them.”

Aguirre, who described Bell as a “great” mentor, suggested that Bell and the stickleback are inextricably intertwined. “The threespine stickleback is truly one of evolutionary biology’s supermodels and [Bell] has played a critical role in bringing the species to the attention of the broader scientific community and the general public.”

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From left, Ellen Li, Jennie Williams and Ping Ji, a technician (sitting). Photo by Daniel Irizarry

It’s a dream team tackling a nightmare scenario. While colorectal and pancreatic cancers are killers across different races, they are considerably worse for African Americans.

African Americans with colorectal cancer are about 40 percent more likely to die from it compared to those from other racial groups, according to recent data from the Surveillance, Epidemiology and End Results Program. The incidence of pancreatic cancer in African Americans is also 31 to 65 percent higher than in other racial groups.

A Stony Brook University research team led by Ellen Li, a professor of medicine and chief of the Division of Gastroenterology and Hepatology, is trying to understand the causes of these variations and, in the process, hopes to provide the kinds of clinical benefits that would help everyone.

“We think there are multiple factors,” Li said. Scientists at Stony Brook, Cold Spring Harbor Laboratory and SUNY Downstate Health Disparities Center are creating one of “the most comprehensive data sets” that people can analyze.

The team includes Jennie Williams, an associate professor in the Department of Family, Population and Preventive Medicine, Joel Saltz, the chair of Bioinformatics at Stony Brook, Richard McCombie, director of the Stanley Institute for Cognitive Genomics at Cold Spring Harbor Laboratory, David Tuveson, the director of the Lustgarten Foundation Pancreatic Research Laboratory at CSHL and several other researchers at  Downstate.

Williams said she began reading up on the response to cancer treatment by various groups in 2004. She understood that African Americans don’t respond to numerous chemotherapy prevention agents and some treatments for colon cancer. “They either don’t respond or they become resistant to chemotherapy,” she said.

When Williams started looking into this in 2008, she focused on microRNAs, which bind to messenger RNA and suppress translation. MicroRNAs are noncoding regulatory RNAs. The dysregulation of these important sequences result in the silencing of tumor suppressor proteins and the overexpression of oncogenes.

Her biggest finding was that the expression of tumor suppressor proteins inversely correlated with the overexpression of a microRNA called miR-182. This microRNA, she said, was significantly higher in tumor samples from African Americans.

With a molecular target and a potential mechanism, Williams thought she was well on her way to digging in. She ran into a significant stumbling block, however. “To do cancer chemotherapeutic studies, you need cell lines to work with,” she said.

Williams went to several companies to find colon cancer cell lines and asked, specifically, for those from African American patients. She found that the only cell lines labeled with race were those from Caucasians.

“To study chemoresponse, one needs a broad spectrum of cell lines,” Williams said.

She started generating cell lines in her lab, with three from African Americans and two from Hispanic patients, as well as some from Caucasians.

While Williams said she loves living in Stony Brook, she has found the lack of diversity among the patient population limiting in addressing cancer racial disparity. With Li’s help, she partnered with Downstate, where 75 percent of the patient population is African American.

She hopes to generate 10 African American, 10 Hispanic American and 10 Caucasian cell lines. Stony Brook and Downstate will collaborate to exchange ideas and personnel.

Williams said part of the challenge in gathering tissue samples from the African American population comes from a history of worrisome interactions with scientists.

Many African Americans have heard of the Tuskegee Institute study of African American men who came to the institute with syphilis between 1932 and 1972 but were not treated with penicillin, even after the drug became an effective and standard treatment in 1947. When the public became aware of the study, it ended and the government established strict informed consent rules about participating in scientific research.

Li said in their study on racial disparities in gastrointestinal cancers, selected staff certified in human research de-identifies everything so no one knows who each participant is. The data collection is a labor-intensive work, Li said, that is designed to provide greater insight into what might be causing these differences.

In terms of explaining the differences, Li and Williams believe it is both “genetic and epigenetic.”

In Africa, colon cancer is rare compared to its occurrence in the United States, Williams said, which suggests that diet and lifestyle contribute to the disease and its progression.

Raised in Savannah, Georgia, Williams said she was always interested in what made things change, from the tadpole in the pond to insects and birds that flew. While her parents didn’t attend college, that wasn’t an option for her: “It was never if” she went to college, “but when.”

Li, who is married to Stony Brook President Sam Stanley and has four children, said health insurance is one of numerous problems that affect individual populations. Numerous other factors could play a role in explaining the racial disparities in cancer outcomes.

Diabetes, which occurs at a higher rate in African Americans, increases the risk of colon cancer, Li said. It is unclear how much the incidence of diabetes in the African American population may contribute to the disparity, Li said.

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Linda Van Aelst photo by Michael Englert/CSHL

Countless forks in the road lead to the creatures that swim, crawl, walk, and fly around the Earth. Some of these moments have a significant effect on the fate of the individual, taking it from the early stages when it’s filled with potential into a bone, a muscle or a brain cell.

In some cases, the process goes off track. The signals, pathways and processes take a different turn, sometimes because of a change in a gene or a protein.

Linda Van Aelst, a professor at Cold Spring Harbor Laboratory, explores how changes in intracellular signaling involving enzymes called small GTPases can lead to disease. She and her team of six graduate students and postdoctoral researchers focus on Ras and Rho GTPases and their regulators, which control cellular growth and the kinds of changes that lead to the shapes of cells, organs or tissues.

Alterations in the genes involved with these enzymes can lead to a range of diseases. “Mutations have been linked to cancer-related processes, including metastasis, as well as to neurodevelopmental and neurological disorders,” Van Aelst said.

Bo Li, an associate professor at CSHL, suggested that Van Aelst, who provides guidance and direction as his mentor, is a leader at the 125-year old research facility.

Van Aelst is “well known for her innovative work on signaling molecules in the cell, including Ras and Rho,” Li said. Her work is “really innovative.”

Van Aelst studies these enzymes by taking what she described as a “bottom up” approach, exploring their development and their role in cellular and developmental processes in the context of the brain. She explores how any perturbation can affect behavior and, once she sees a change, looks for differences in the circuitry development.

Van Aelst looks at the process from the beginning, with the genes, through the protein network. She has sought to understand how some changes lead to metastatic cancer that spreads to a single organ, while others spread generally throughout the body.

Because she is exploring mutations at a basic level, Van Aelst can get involved in a range of diseases and abnormalities, from epilepsy to schizophrenia to mental retardation to cancer.

“Clinicians send me information and want to see if maybe I can use the tools in different mutations in my research” to understand what might be happening with some of their patients, Van Aelst said.

She also gets calls from the parents and family members of patients, who would like to know if a cure is available for a genetic condition linked to something she’s studied.

Van Aelst knows she needs to be “cautious” because she doesn’t want to give false hope at a time when the research may not have pointed the way towards a specific therapy.

With any clinical trials, she has to “make it clear that the findings are not yet mature enough for further development,” she said.

While she’s conducting basic research to understand the process and mechanisms involved, Van Aelst is aware and eager to help an audience desperate for more information and, down the road, a novel treatment.

She does “see the urgency. It’s important that the patients and the family of the patients and the scientists communicate and it is clear what we understand, what can be done, and how far we can do it.”

Van Aelst hasn’t become involved in a therapeutic study yet, but she has reached the point where she knows aberrations in some processes. She hopes to get engaged in the near future in the next step.

“We don’t have something now in hand, but we have several hints” from cellular processes and proteins, she said.

Earlier this year, Van Aelst and her lab published results in the journal Cell Reports in which they found two proteins that provide a critical role in creating the structure of something in the nervous system called a chandelier cell.

Named for the way axonal arbors branch out, these chandelier cells play an important role in affecting neurons nearby. Their size and structure give them the ability to affect the function of other nerves, either turning them on or off, depending on the signal.

Changes in chandelier cell cartridges and/ or function have been reported in disease states such as epilepsy and schizophrenia, she said.

Van Aelst helped provide an important piece of information about these cells by uncovering the important role two proteins play in their structure.

When the function of proteins called DOCK7 and ErbB4 were disrupted, the chandelier cells have fewer branches or boutons. She discovered that DOCK7 triggers the activity of ErbB4.

Van Aelst’s research on chandelier cells “offers insight into how diseases like epilepsy might occur,” Li said.

Now a resident of Oyster Bay, Van Aelst grew up in the Flemish-speaking part of Belgium and was originally interested in archeology and history.

In biology, however, she was intrigued by how “one gene talks to other genes. How does it work? What does it signal? How does it control this or that function?”

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Dr. Alison Stopeck photo from SBU

Birthdays, anniversaries, weddings and vacations are all important to her. She’s not talking about her own — she wants her patients, some of whom are locked in a battle with cancer, to make it to these landmark events.

Dr. Alison Stopeck, a professor of medicine and the chief of the Division of Hematology/Oncology at Stony Brook University, treats a wide range of people with breast cancer, from those who don’t have cancer but are at high risk of developing it in the future to women and men with all stages of breast cancer diagnosis.

Stopeck said her approach is to treat the whole patient, because she recognizes that combatting cancer most effectively requires care for the physical, emotional and spiritual needs of her patients. Finding out what is important to a patient is “vital to developing the most impactful treatment plan.”

Around Thanksgiving and Christmas, she asks them about their holiday planning and tries to treat her patients around those plans so they can “live as normally as possible” while still receiving breast cancer treatment.

“I do like treating people with metastatic disease,” said Stopeck, who joined Stony Brook last September after a 20-year career at the University of Arizona Cancer Center. “If they come in with metastatic cancer, you can see [tumors] shrink.”

She can also tell patients they are in remission, that the Stony Brook Cancer Center is offering a clinical trial that may be more effective for them, or that there is a new therapy that might work for their particular cancer.

She sees patients with metastatic cancer more frequently because they receive treatment that Stopeck follows closely, so she “gets to know them and their families better,” she said. “It is an honor to develop deep relationships with my patients and their families.”

Dr. Yusuf Hannun, the director of the Cancer Center and Stopeck’s supervisor, praised Stopeck’s passion for her work.

“She is the model that we want to emulate in the development of our Cancer Center,” Hannun said. When Hannun hired Stopeck last year, he had high expectations and he said “she exceeded” those.

Stopeck said doctors can optimize therapy and side effects at the same time. When her patients qualify, Stopeck asks them to go on clinical trials to improve an understanding of the disease. She sometimes also asks for tissue, blood and urine samples so she can ask more questions about the disease and its progression.

While she’s spent years treating patients, she also conducts research.

Stopeck looks at predictive biomarkers, which may help in selecting the best therapy for a patient, while also offering her an early indication of how a treatment is going, so she can stop it if it’s not working.

She is also looking to bring patients into clinical trials.

At Stony Brook, she said, researchers are working on discovering a wide range of breast cancer challenges, including improving treatment for patients with triple negative, which is the most deadly and aggressive form. Studies are also exploring ways to reduce toxicities, including bone pains, of aromatase inhibitors while giving less chemotherapy to patients who don’t need it.

Hannun said the Cancer Center considers clinical trials as “state of the art practice as this is what pushes the envelope and allows patients to be ahead of the curve in their clinical care,” he said.

As a doctor, Stopeck wants her patients to help make informed decisions about their treatment. “Most people think they want to live to 100, but they don’t want to live to 100 when it feels like 1,000,” she said.

Stopeck described how vaccinations for pneumonia have reduced the numbers of deaths from a disease that used to be the leading cause of death in 1900. She wants to figure out how to prevent a person from going through the pain and trauma of breast cancer.

She also explores how some lifestyle decisions can help. At the moment, there is epidemiological data on the benefits of cruciferous vegetables, but no proven research to support their role in preventing breast cancer, she said, which is why she’s studying it. Eating a low-fat diet, high in vegetables along with consistent exercise and a healthy body weight are the best advice researchers have on decreasing breast cancer recurrences.

As for Breast Cancer Awareness Month, in October, she said the funds raised for research can help the scientific efforts. She used a $30,000 grant to develop an imaging protocol to measure breast density safely, easily and comfortably in women. She has used this technology to obtain larger grants from the National Cancer Institute and the National Institutes of Health. For every dollar of private donations invested, an additional $25 in funding can be obtained through the NIH, she said.

Stopeck grew up in Plainview in the same house where her parents still live. She moved to Farmingville from Arizona last September. She loves animals and enjoys traveling. The fact that her parents and sister live nearby make her feel as if she’s “coming back home.”

In her research and clinical practice, she has an ambitious and unambiguous focus. “My goal is simple: treat, cure and prevent breast cancer,” she said. “I live it and breathe it every day.”