Power of 3

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With ‘veto power,’ chandelier cells are theorized to keep order in the nervous system

Someone whose opinion he trusted told him he was going in the wrong direction. Every indication for years suggested success was as elusive four years after failing as it had been during his first unsuccessful attempt.

“It didn’t look very good,” confided Z. Josh Huang, a scientist at Cold Spring Harbor Laboratories. In those first years, he wondered if he should do something else.

Sticking with it, however, paid off, especially in the last few years. Huang and his team have made important discoveries about a type of neuronal cell in the cerebral cortex called chandelier cells.

Huang has not only been able to label these cells and watch them in action, but he has also figured out where and when they develop, before they move to their position inside the cerebral cortex (the part of the brain that is responsible for processing sensory information, for thinking and reasoning and for directing movement).

These chandelier cells are likely to be the most powerful cells in the cerebral cortex. They are only found in the cerebral cortex and humans appear to have more of them than other mammals, including monkeys and mice.

They got their name from the way their branches jut out from the main body of the cell. Their axon arbor looks like a chandelier light. Researchers believe they serve an important role in keeping order in the nervous system, quieting other nerve cells from vying for attention all at once.

Francis Crick, who won the Nobel Prize in 1962 for discovering the double-helical nature of DNA with James Watson, first suggested four decades ago that these cells had “veto” power, according to Huang.

“When the chandelier cell ‘speaks,’ it is like the president. All these other cells will be quiet, regardless of their urge to speak,” Huang explained.

While that metaphor hasn’t been proven precisely yet, Huang said the evidence is mounting to support Crick’s original contention. Huang’s research is testing this specific assertion.

Some medical challenges, including schizophrenia and epilepsy, have been linked to problems with chandelier cells.

“A variety of molecular markers were altered or reduced in the pre-frontal cortex in schizophrenia patients,” Huang explained. “That has been a very reliable finding from many labs.”

The possible explanation is that if these cells are compromised, the excitatory neurons will not function coherently. Some treatments are looking at ways to boost the output of the chandelier cells by enhancing the so-called GABA receptor.

GABA, named for the neurotransmitter gamma amino-butyric acid, is the only inhibitory neurotransmitter in the brain. GABAergic inhibitory cells, including chandelier cells, organize neuronal populations into groups that guide behavior.

Some of Huang’s early work, which proved so challenging, involved following the pathway of these chandelier cells, which develop outside the cortex and move to their central locations during development. When he started looking for ways to track these cells, scientists were using dyes, which weren’t reliable.

Huang built a better animal model system to track these cells. Now, he can see them every time they are active.

“You can activate them or silence them and see the consequence,” he explained. “It’s extremely powerful.”

In the latest finding, Huang discovered that these important cells start out in a region of the embryonic brain he called the ventral germinal zone. This part of the brain didn’t have a name because it wasn’t clear what types of cells it produced.

Chandelier cells are “born” after another region that is responsible for producing different neurological inhibitor cells disappears.

Huang’s work was published last month in the journal Science. Earlier this year, he also served as co-author on three papers in Nature, another prestigious scientific journal.

“This has been an amazing year,” he concedes. “It took us four years to fail, to build this experimental system” to make these findings.

Huang, who has been at Cold Spring Harbor for a dozen years, lives in Woodbury with his wife May Lim, a radiation oncologist in Queens, and his two daughters, Vivien, 12, and Julienne, 8.

In graduate school, he added the first name “Josh” because it has some phonetic resemblance to his Chinese first name.

In terms of his research, Huang said he received supportive advice from colleagues and advisors along the way, much of which he took to heart during the years that weren’t quite as productive as this one.

“What I came away with is to do something that is very fundamentally important and to stay the course,” he offered.

 

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Using nanotechnology he and other scientists hope to lessen our dependence on fossil fuels

When he was in secondary school, Alex Orlov and his family had to take an unusual device with them to shop. While his parents checked how ripe and fresh the fruits and vegetables were, they also put a Geiger counter near each item.

Orlov grew up in the Ukraine — only 60 miles from the site of the 1986 Chernobyl nuclear power plant explosion. In the first few weeks after the explosion, food and milk at farmer’s markets in Kiev, the capital of the Ukraine, wasn’t screened for radiation.

“If a potato had too much radiation, we didn’t want to buy it,” he said. Orlov’s mother, who was a doctor, went into the exclusion zone after the explosion to treat firefighters and police officers who, he remembered, sometimes fought radioactive flames with a hose and water.

Greatly affected by the dramatic events that caused his family to evacuate their home in Kiev for six months, Orlov went on to become a scientist, where he combines his interests in energy and the environment.

An assistant professor of Materials Science and Engineering at Stony Brook, he is working on a range of projects, including some that may one day reduce our dependence on fossil fuels and whose byproducts may include water, instead of greenhouse gases like carbon dioxide.

Orlov recently teamed up with colleagues from SBU, including Peichuan Shen and Shen Zhao from the Department of Materials Science and Engineering and Dong Su from the Center for Functional Nanomaterials and computational scientist Yan Li from Brookhaven National Laboratories, on research with incredibly small amounts of gold.

As it turns out, the properties of the precious metal change when there are only a dozen or so atoms. For starters, instead of being shiny and yellow, the way it is when it adorns an ear or flashes from a finger, it can appear red, blue or other colors on that small scale. More importantly, though, the gold atoms are much more reactive. When exposed to light, they can help break apart water, which has two molecules of hydrogen and one molecule of oxygen, into its different elements.

The gold is 35 times more effective than ordinary materials, such as the naturally occurring mineral cadmium sulfide, at separating water.

Hydrogen, the lightest element in the periodic table, can be a clean-burning fuel, producing water as a final combustion product.

The results were “very unexpected,” he said. “People used nanotechnology before and they might get a single digit improvement.”

Orlov said there is considerable work ahead before this process has practical application, although he does keep that goal in mind when he approaches his research.

He is going in “about a dozen different directions” as he explores other possible materials that might generate fuel, he said.

The commercial world has already embraced nanotechnology in several other arenas and has figured out how to make these miniature reactions scalable.

Orlov has advised one company, called PURETi, that produces a coating for buildings that will make them self-cleaning and air purifying. Nanotechnology is also used in industries ranging from cosmetics to health care to car manufacturing.

Nanotechnology has had “an immediate impact in everyday products.”

While gold may prove prohibitively expensive to generate hydrogen fuel, these experiments may provide a footprint to find other materials that could be just as effective.

“The devil is in the details,” Orlov suggests.

Orlov, who earned a Ph.D. and one of his three master’s degrees at the University of Cambridge, has coupled his interest in energy and the environment to serve as a scientific advisor to world leaders. Prior to his taking office as prime minister in the United Kingdom in 2010, David Cameron asked Orlov to serve as policy advisor for science, engineering and technology policy development. Nowadays, he travels to the UK every three months, where he advises on hazardous substances and the environmental impact of nanotechnology.

A resident of Smithtown, Orlov has been at Stony Brook for about five years and has been inspired by the interdisciplinary opportunities at the university and the affiliations with nearby institutions.

“Researchers from the top 10 institutions in the country are coming to Stony Brook” in part because of the connection to BNL, he said. “We couldn’t wish for better facilities.”

As for his research, Orlov recognizes — after his experiences in the Ukraine — that there is an ongoing need to balance the energy benefit of any new technology with its potential environmental
impact.

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Distant clouds, light and shadows, black energy are all part of his research

Anze Slosar has his head in the clouds. No, not the ones that drop rain or that provide a welcome respite from the sun in July, but the ones at the edge of the universe, as many as 11 billion light years away.

An assistant professor at Brookhaven National Lab, Slosar is a cosmologist who looks at the way hydrogen clouds absorb light and change its color as it makes the long journey to Earth.

The way light from quasars — bright regions that can be a trillion times brighter than the sun — passes through hydrogen gas clouds helps paint a picture of the expanding universe.Slosar will be examining light from thousands of points of light to create a three dimensional map. He is currently analyzing 60,000 quasars and has another 100,000 in hand.

“I sometimes fool myself into thinking I’m like Christopher Columbus, discovering new structure in the world,” he offered.

He looks at the graphs that show statistical properties of those clouds. Slosar’s promising work in creating maps with the Lyman Alpha Forest — as this technique of using the shadows through hydrogen gas to recreate maps of the early universe is known — has earned him distinctions.

Last year, his proposal was one of only 65 chosen for funding from 1,150 submitted by researchers around the country. The funding will support five years of research.
He likens his efforts to put together a picture for a Chinese puppet show, where he sees traces of objects through the clouds.

He is participating in the Sloan Digital Sky Survey, which operates one of the world’s largest digital cameras, based in Apache Point, N.M. Slosar said he doesn’t look through the lens of the telescope at the images. Rather, he collects the digital data and uses computer programs to analyze, interpret and make sense of the nature of the universe.

The universe had a tremendous explosion of energy — the Big Bang — billions of years ago. After the Big Bang, the pieces of the universe would be expected to stop moving away from each other, and might even turn over and begin to collapse, he explained. Instead, they are expanding at an accelerated rate.

Physicists believe so-called dark energy is responsible.

Explaining dark energy using familiar objects, Slosar suggests “imagine throwing a stone in the air. You would expect it to slow down completely and start returning. You could also expect it to never return if you threw it so energetically that it would leave the Earth and travel in empty space. However, you wouldn’t expect it to suddenly start to speed up and this is what is happening with dark energy.”

“It’s undeniably there,” Slosar said. “You can’t touch it, but we can measure its effects on the expansion of the universe.”

While he feeds his scientific interests by looking back in time at a map of the universe, he said the pursuit itself includes challenges and frustrations.

More often than he’d like, he comes to his office and sits “at my computer and I swear, because the program doesn’t work the way it should,” he laughed.

Slosar recognizes the pursuit of basic science itself doesn’t improve the productivity of a crop, lower the cost of gasoline or create a sturdier structure that won’t collapse in a strong wind. It can and does provide other benefits, including feeding the minds of those curious enough to ask questions about the universe.

“There are always nice side effects from science,” he said. “The Internet came from fundamental research. The side effect of developing rocket science is going to the moon. Whenever you try to do something hard, you inevitably learn new things.”

A permanent resident of the United States, Slosar lives in Queens with his wife Maja Bovcon, who was his high school sweetheart when they grew up in Slovenia. Bovcon got her Ph.D. in political science from Oxford, while Slosar earned his doctorate from Cambridge “as if we were both British aristocrats, but instead we are from working-class families from Slovenia.”

Bovcon is at the end of a three-month-long study in Senegal.

Slosar explained that his work is “trying to make sense of how the universe behaves as a physical system. What is it made of, how did it begin and how will it end up?”

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Not only treatment, but early diagnosis is a challenge in dealing with this tumor

It’s an all-too-familiar pattern. Someone he’s never met reaches out to David Tuveson for his opinion. After exchanging emails or talking on the phone, Tuveson gets an update from a friend or family member: they buried the person who sought his help. He or she died from pancreatic cancer.

“It’s gut-wrenching,” he declared.

A scientist and doctor at Cold Spring Harbor Lab, Tuveson is leading a team of researchers to tackle pancreatic cancer, the most lethal form of cancer.

A world-renowned expert in pancreatic cancer, Tuveson recently opened the Lustgarten Foundation Pancreatic Research Laboratory, where he will direct research on ways to improve medical knowledge of a cancer that kills 250,000 people worldwide each year, including 37,000 Americans.

While that number is smaller than lung cancer, it also carries a more daunting prognosis. Using current treatments, only 6 percent of people with pancreatic cancer survive five years after their diagnosis.

The pancreas is an organ below the stomach that produces hormones including insulin and makes digestive enzymes.

Pancreatic cancer presents several challenges. For starters, it’s difficult to diagnose. The symptoms, which can include abdominal pain, diarrhea, jaundice or weight loss, often appear at a point when the cancer has already progressed.

Scientists at the lab are looking for ways to spot the presence of pancreatic cancer early through blood or urine samples, in much the same way doctors check for cholesterol levels, blood sugar and blood pressure to look for signs of heart diseases.
Pancreatic tumors themselves are also difficult to penetrate.

“The tumor is hard, like a rock,” explained Tuveson. “Other tumors are soft, like a grape.”
Pancreatic tumors have a type of cement between the cancer cells called stroma. That makes it difficult for vessels to pump blood. Even the most effective medicine would need some way to loosen the stroma to deliver targeted tumor toxins. Tuveson and others have shown that drug delivery is limited in pancreatic cancer.

Indeed, one recent study tested the hypothesis that drugs aren’t getting into the tumor.
This was “the first clinical evidence” in an early-phase trial that drugs aren’t reaching their targets, Tuveson offered. The study should be completed within a year. “This is giving us hope that the science we’re doing is correct. Now, there are a variety of ways to increase the delivery of our therapy.”

Tuveson and his colleagues are looking for ways to develop new drugs.

“We are taking novel platforms and novel payloads that can bind to and inactivate the root causes of cancer,” Tuveson explained.

He is inspired by the opportunity to work with people throughout Cold Spring Harbor, including professors Gregory Hannon, who has done innovative work with RNA, the cousin to DNA, and Adrian Krainer, who has worked with antisense therapies.

Asked to compare the task of diagnosing and treating pancreatic cancer to climbing a mountain, Tuveson suggested that researchers don’t know how far or high they have to climb to understand and conquer this cancer.

“We are scaling this mountain, but no one has ever climbed it,” he suggested.

Tuveson recognizes it’s likely to be a steep ascent.

“Some would say what we’re attempting is not possible,” he said. Many have tried and failed to solve pancreatic cancer, he explained. Tuveson, however, said he ignores the naysayers and feels fortunate for the support of Cold Spring Harbor and the Lustgarten Foundation.

He is inspired by the resources, the energy, and the talent in a lab that includes postdoctoral students, Ph.D.s, and technical staff. If these approaches are effective, they might help in treating other forms of cancer.

Tuveson, who lives on the Cold Spring Harbor campus with his wife Michelle, explained that his early training in medicine prepared him for the interactions with patients and their families when they face the daunting challenge of a pancreatic cancer diagnosis.

“When I was training as a physician in East Baltimore in the late 1980s, a lot of my patients were dying from this new disease no one knew much about, which became known as HIV,” he recalled. “When that happened, I convinced myself I would be an HIV doctor.”

By the time he started his residency in Boston, medicine had come up with treatments for HIV.

“When I went through that very young, I became interested in being a healer,” he said. “I learned how to talk to the families of patients. I became a doctor for the family, equally or more so, than a doctor for the patient.”

As for his pancreatic cancer team, he said he is eager to make progress in understanding and conquering this lethal form of cancer.

“I am the most excited I’ve been in my career,” he explained.

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Decreased sardine yield and rising water temperatures are part of global warming trend

As if the southern Caribbean weren’t already hot enough, the water temperature has climbed in the last 14 years at the same time that trade winds have weakened. While this may sound encouraging to scuba divers, it’s not such good news for plankton, the sardines that feed on them and the Venezuelan fishermen who depend on these small fish for their livelihood.

Above the Cariaco Basin, an ocean trench a few miles offshore from Venezuela, a local decline in trade winds has limited the movement of nutrient rich waters, contributing to a reduction in plankton production and, in part, to a collapse in local sardine fisheries, according to research by Gordon Taylor, a professor of microbiology at Stony Brook’s School of Marine and Atmospheric Sciences.

Working in collaboration with Mary Scranton, a Stony Brook professor, as well as researchers at several other U.S. and Venezuelan institutions, Taylor has traveled from Stony Brook to Venezuela every six months, monitoring oxygen, carbon, sulfur, nitrogen and other metals in the water, as well as the abundance and growth of microorganisms from the surface to the sea floor.

The decline in sardines, as measured by some of Taylor’s colleagues, has been dramatic. Sardine fishery landings were 40,000 tons in the last year, down dramatically from 200,000 tons in 2004. Overfishing also contributed to the steep drop.

Slower trade winds are a problem for the region because they interfere with a process called nutrient upwelling. The deeper, cooler regions of the ocean have more nutrients because that’s where plants and animals decompose. As this living matter sinks, it releases “the Miracle-Gro of the ocean,” Taylor explained.

The chemicals involved in water cycling through the ocean include nitrogen, phosphorous, silica and trace metals — some similar components people put on their lawns or potted plants.

The nutrients in the colder water typically cycle towards the surface. In upwelling, friction from winds pushes surface water away from the coast. That brings deeper, nutrient-rich water to the surface to replace it. With the change in the winds, the nutrients don’t reach the basin.

At the same time, the temperature of the water has increased by about 1.1 Celsius degree. While Taylor acknowledged that “1 degree doesn’t sound like a lot,” he urged people to “keep in mind that 1 degree represents a tremendous amount of heat being stored in the ocean.”

Global warming is causing both the higher water temperatures and the change in the trade winds, Gordon asserted.

“All indications from the International Panel on Climate Change is that the heat budget for the planet is on a one-way track at the moment because of fossil fuel combustion,” he said. “We continue to add more carbon dioxide to the atmosphere much faster than it’s being consumed.”

The Stony Brook professor said he has been aware of climate change for four decades, but his research has helped him understand the pace of that change.

“I was aware of the Greenhouse Effect back in my college days in the 1970s,” he indicated. “However, I remained skeptical about how fast it may be occurring, its dangers and didn’t appreciate the many ramifications of climate change until about 15 to 20 years ago.”

His studies, however, suggested “how fast the effects can be detected in the Tropics.” He cautioned that once the planet crosses a tipping point, the ecosystem can enter a “new state in a very short amount in time.”

Taylor lives in East Setauket with his wife, Janice, and their Rhodesian ridgeback dog, which is all of 113 pounds and is still not fully grown.

Their daughter Olivia just completed a program in fine arts. She lives in Manhattan, where she paints and sculpts, and works in a clothing boutique in SoHo.

Taylor has also studied the western part of the Long Island Sound, where he has examined the physical, chemical and biological causes of low oxygen levels, or hypoxia.
Taylor enjoys traveling to Venezuela, where he can continue to gather information, visit with colleagues, and study an area that he’s gotten to know well over the more than a decade since he started collecting water samples.

He has a “terrific set of friends” that he started this project with and, because he’s been doing this for so long, they’re all “growing old together.”

The microbes that are the subject of his work and his teaching at Stony Brook “are underappreciated,” he suggests. “We all owe our existence to them.”

Correction:
In the Power of Tree column that ran last week (Nov. 22), the caption for Esther Takeuchi incorrectly indicated her location. She was in her lab at Stony Brook University. She has a joint appointment from SBU and Brookhaven National Laboratory. The photo was provided by SBU. We regret the errors.

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Work leads to understanding how viruses infect cells; has potential for correcting genetic disorders

With their miniature parallel tracks twisting and turning and their connections in the middle, the structure looks like a winding ride. As it turns out, it is, although not for humans.

Using an 11-amino acid sled, viruses shuttle proteases along the double helical structure of DNA, enabling them to infect other cells.

Leading an international team of researchers, Walter Mangel, a biophysicist at Brookhaven National Laboratories, recently found the sled that slides along the phosphate spine of DNA. It carries a protease important in the activation of a virus to its destination.

When the protease and another protein collide on DNA, it begins a reaction that leads to the removal of clumps of proteins that support the construction of viral DNA.
Mangel likens the proteins that are cut away to the scaffolding builders use when they put together a cathedral. With the scaffolding in place, the viral DNA can’t become an effective invading genetic force.

“We took a model virus, one that was not dangerous to work with, and we wanted to understand how this protein functions,” Mangel said. “If we do, we can inhibit that protein.”

The researchers chose the adenovirus, which causes common colds, pink eye, blindness, weight gain and diarrhea.

The molecular sled moves by thermal (i.e. heat) energy and doesn’t use miniature wheels to move along the track, but rather has electrical charges that keep it stuck to the DNA. The sled has four positive charges that interact with the negatively charged phosphates in the major groove of the DNA.

“The sled enables the molecule to collide with another molecule on DNA,” he explained.

Once the protease removes the scaffolding, the virus can infect other cells. Mangel said the concept of a molecular sled came together in his mind when he was visiting a museum in Vermont that had farm equipment. He saw a large sled and realized this was likely how these proteins were navigating through the nucleus to their destination.

“Once we saw the 11-amino acid peptide slide by itself, we thought it might be a sled,” he said. This molecular sled not only could transport molecules to the right destination in the DNA, but could also ensure that they collided in a way that ensured a reaction would take place.

In a solution, molecules typically only bind to each other when they collide at a specific speed at particular sites on their surfaces. In most collisions, even those molecules with complementary functions recoil. If both molecules are stuck to DNA and one or both slide on the sled, the speed of the collisions is set by the speed of the sled.

“This could give rise to chemistry that is far more efficient, in which almost all collisions by sliding lead to binding,” Mangel said.

While researchers will try to disable or deactivate the sled — perhaps by attaching other blocker molecules to keep the protease from navigating down to its spot on the viral DNA — they may also find ways to use the sled.

“The sled is capable of carrying anything attached to it,” Mangel said. That means it could be used in transgenic therapy, where doctors and scientists may want to replace one genetic sequence for another, potentially correcting a genetic disorder.

Mangel explained that the experiments with the molecular sled took considerable collaborative coaxing. He wrote to 10 labs that had equipment that would allow him to do single molecule experiments. When he spoke to Sunney Xie at Harvard, a partnership began.

The first set of experiments in Massachusetts failed.

He had planned to return to Long Island the next day, but wanted to try one last experiment, in which he increased the acidity of the solution. Immediately, he saw considerable sliding.

Mangel lives in Shoreham with his wife Anne. They enjoy running together and visiting the beaches and parks in the area, especially along the east end.

Mangel is a fan of opera and classical music and has conducted his work while listening to classical music from a BBC station. He also is an avid artist and has sketched his colleagues in the lab.

The direction of his work and his artistic interested collided when he discovered the use of this molecular sled.

“What comes out of the work is rather simple,” he said, alluding to the sled. “The experiments are sophisticated to support that theory.”

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Strokes, cancer and other diseases can be more accurately studied and treated with new technology

Yingtian Pan works at the cutting edge of biological imaging, looking with increasing breadth and depth into cells ranging from bladder cancer to diabetes. Congwu Du, meanwhile, who has also done imaging, has studied the effects of cocaine on the brain.

One night, Du suggested the two Stony Brook scientists, who met when they were undergraduates studying biology in their native China, work together to get a better view of how blood flow changes in the brain after cocaine use.

Strokes, in which brain cells die because they don’t have enough oxygen, are one of the most serious medical risks of cocaine abuse. Getting a closer look at blood flow in the brain might suggest how these strokes develop.

Pan didn’t take too long with his decision. After all, he said he was eager to collaborate with Du, who isn’t just his professional colleague, but is also his wife and the mother of their two children.

Using animal models, Pan and Du employed 3D optical Doppler imaging tomography to look closely at the effect of cocaine on cerebral blood flow. Sure enough, even a single dose of the drug causes the flow to decrease. The scientists observed a disruption in some terminal arterioles and the connecting capillaries.

“When cocaine is administered, it causes constriction,” Pan explained. “The local brain oxygen is reduced.”

Cerebral blood flow decreased by as much as 70 percent within two to three minutes after a dose of cocaine. While the blood flow often returns to normal within three minutes, some flows were shut down and did not come back for at least 45 minutes. The delayed recovery was a new observation, Pan explained.

Another dose of cocaine soon thereafter causes the area with restricted blood to grow like a cloud.

“We see more of this shutting down” of blood flow, Pan commented. “That’s very unhealthy. There’s a long period of time with very low oxygen supply.”

The next step in this research is to look at the effects of longer-term cocaine abuse.
Pan, who has been at Stony Brook since 2002, has applied his imaging skills to a wide range of projects.

He worked on bladder cancer, which, if detected early, can have a good prognosis but becomes much more problematic if it progresses without intervention.

Using optical coherence tomography, which is similar to the Doppler technology he used for the cocaine study, Pan was able to increase the reliability of determining cancer screenings from 75 percent to 94 percent for sensitivity.

While some scientists have called this type of screening optical biopsies (i.e. looking closely at suspected cancers without removing any living tissue and screening it in at pathology lab), Pan is cautious in his use of that term.

“The issue with any new technology is that before it’s been clinically approved and without histological (or cellular) proof, we haven’t reached that stage yet,” he explained.

With these images, however, doctors can be more specific and targeted in their approach to bladder tumors. The next step is to provide computer-aided diagnosis to physicians for more accurate diagnosis in the operating room and for outpatient facilities.

Pan has also worked with wound healing for people with diabetes. By using imaging technology, doctors can monitor every lesion and can understand the exact benefit, or lack thereof, of any potential drug.

At this point, that work was limited to an animal model to track the growth of skin under different bioactive implants.

He has also worked on interstitial cystitis (also called IC, a condition in which people can feel intense pain in their bladder when they urinate) and geriatric incontinence.
Pan said he has found collaborators by building up a network of fellow researchers, many of whom approach him with imaging questions and opportunities.

“We hope we can provide a device to physicians,” he said. “We need to give them some understanding of the technology so they can get a good idea of how to interpret the images.”

Eventually, Pan expects that this technology, which is already widely used in eye clinics, will become similar to ultrasound in its medical usage. While it has high resolution, its image depth is limited depending on the type of tissue.

Right now, the field is very competitive, with scientists around the world looking for better, clearer, and more specific images of biological systems.

“We like competition,” he offered. “It means we have to work hard.”

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Engineering hardier plants could feed a growing population or provide biofuel

The sports adage, “it’s not the size of the athlete in the fight, but the size of the fight in the athlete,” might apply to Ben Babst’s research.

Instead of studying athletes, the Brookhaven National Laboratory researcher is looking at something that fights numerous unseen battles — plants.

A postdoctoral fellow at BNL since 2010, Babst uses positron emission topography scans to track how labeled elements move and change as they go through plants. This is the same technology doctors use to test for breast or lung cancer.

Babst is examining corn, sorghum, grasses and some of their relatives to understand how they grow and respond to their environment. He is also looking at what makes some grow bigger than others, while others tolerate drought or low-soil nutrients.

“We need to understand the underlying mechanism for fast growth, for stress tolerance, for pest resistance,” he offered. “We are not only measuring how big they are or how they look, but what they are doing inside. [We are looking at] what is happening with their metabolism and with signaling.”

The benefits of understanding plant growth apply to the conversion of plants to biofuels and the expansion of previously unused or undeveloped land for agriculture. Down the road, this could enhance our ability to generate plants to feed the increasing global population and to provide alternative, sustainable energy.

“One of our major goals is to come up with new strategies to find or engineer plants that can grow vigorously on lands not useful for food production,” he explained. “Another goal is to find new strategies to develop plants that have a biochemical composition favorable for conversion to fuel, for example high sugar or starch content.”

The challenge is to combine all the desirable traits into one crop.
Through agriculture, farmers have gone through a selection process that might not benefit the plants, or us, in the long run.

By watering, fertilizing and using pesticides to get rid of insects, bacteria and fungi, we have produced plants with an unintentional loss of hardiness. By cultivating plants under these conditions, we may have diminished the resistance plants might have to some of these challenges.

Babst and his colleagues are studying plant hormones, called phytohormones, to see how they protect plants. The plant hormones might tell a tree in a drought to close the pores on its leaves to prevent water loss.

“A recent new direction for the group is that we’re using carbon 11 [a radioactive carbon that’s easy to see with the advanced technology] to label specific phytohormones and biomolecules,” he explained. “We are looking to see how the phytohormones are made and if, under different treatments, they are made at different rates.”

He is also looking at movement of the phytohormones because the rate of that movement might determine their effect.

Babst started working with PET when he did his Ph.D. research at Tufts University. While he was there, he simulated an insect infestation with plants to determine their reaction. To his surprise, the plants in his experiment hid some of their precious resources in their roots, farther away from what they perceived as a threat from insects that might steal their sugars.

“I had a different project goal in mind,” he recalled. “When I saw that plants were bunkering their resources down in the roots after a herbivore attack, I was pretty excited. It changed the course of my research.”

In addition to seeking basic information about plant growth and metabolism, Babst also hopes to contribute to an understanding of how to harness plants for biofuel and how to help find plants that might grow in areas of the world people had once thought couldn’t sustain plant growth.

“Energy is central to our economy and has an impact on everybody’s everyday life,” he said. “I’ve noticed [in recent years ] that every time the economy seems to get moving, gas prices and energy prices go up and that muzzles economic progress.”

A married father, Babst lives in Manorville with his wife Clare Norcio, an adjunct professor of history, and two primary-school children.

He recently took his children to the pumpkin festival at Suffolk County Farm. He enjoys hiking along some of the trails on Long Island.

“When I see plants, I see one that looks stressed, or one that has caterpillars that have mauled it. Sometimes, I see it for its beauty. I’ll see an understory plant that looks so tiny but is probably decades old.”

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Shinnecock Bay gets help from Christopher Gobler, Ellen Pikitch and their team

Christopher Gobler is tired of being the bearer of bad news for Shinnecock Bay. Every time someone wants to talk about ecological problems in the bay, they reach out to the Stony Brook scientist for information.

Gobler finally has some good news to share. He and a team of scientists at Stony Brook received a $3 million grant from the Simons Foundation and a private donor to turn the tide in Shinnecock Bay. Through a five-year plan, Gobler and fellow scientist Ellen Pikitch are leading an effort to restore the water quality and improve conditions at Shinnecock Bay. They hope their efforts will allow the bay to sustain larger populations of shellfish and finfish.

“We’re trying to do something to improve and reverse the things that have happened in the bay,” Gobler offered.

The effort was funded by a philanthropic gift from the Laurie Landeau Foundation, matched by similar funds from the Simons Foundation.

The eastern-most lagoon along the South Shore estuary system, Shinnecock contains 9,000 acres of open water, salt marshes and intertidal flats.

The bay, which was once home to a thriving range of shellfish, has had a decline in water quality because of the run off of nutrients like nitrogen and phosphorous, especially from septic tanks. Researchers believe nitrogen loading and the absence of shellfish are the biggest contributors to toxic red and brown tides, Gobler said.

“Part of the problem is that there’s stuff going into the bay” that leads to algal blooms, he offered.

Shinnecock is a tale of two bays. On the eastern side, it’s still closer to the best of times, as ocean water flushes through every day. The west side, however, is suffering through closer to the worst of times, as nutrients introduced by human actions remain in the bay for over a week because of less active ocean cleansing.

Researchers at Stony Brook’s School of Atmospheric and Marine Sciences plan to turn that around. The first step involves restocking shellfish, which will filter the water, and replanting eelgrass beds. This will create habitats for juvenile fish, which can hide from predators.

Scientists will also bring seaweed into the bay, which will act as a sponge, taking out the nutrients that lead to these red and brown tides. The scientists will remove the seaweed once it has absorbed enough nutrients, and will bring in a fresh batch.
Researchers like Pikitch and Gobler will monitor the bay regularly.

“This will be a continual effort we will build on,” suggested Gobler, a graduate of Ward Melville High School who now lives in East Quogue with his wife Dianna Berry and their three primary school-aged children. “We’re starting out with hard clams and oysters.”

Pikitch has already started surveying fish throughout the bay and has found, as she expected, that there is a greater range of fish living in the eastern part of the bay, where the water quality is considerably better.

Pikitch expects improvements in water quality and an expansion of a healthy habitat throughout the bay to foster growth of a broad range of fish.

“As water quality improves and as eelgrass beds flourish, fish will be able to reproduce, hide from predators, and grow,” she suggested.

Stony Brook University President Samuel Stanley hopes the restoration effort will “serve as a template for similar projects worldwide,” he said in a statement.

Those interested in learning more about the restoration program can visit the website www.shinnecockbay.org.

Pikitch, who lives in East Quogue, said one of her favorite activities is to take her grandchildren to the ocean, where she hopes they fall in love with it at an early age, the way she did.

“I worry about what kind of world my grandchildren will grow up in,” she offered. “I worry about harmful algal blooms. I wonder: What if we didn’t do anything and things got worse.”

If, she added, “the bays aren’t healthy, we won’t be healthy.”

She said she feels a sense of urgency about her work. After all, humans caused the problem and we should be able to turn it around, she offered.

“We’re going to make a big dent,” she predicted. “This is a problem that can be solved.”

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Learning how cells cross the blood-brain barrier may help with neurological diseases and injuries

Brains have a security system that is similar to that of a plane’s cockpit. Everyday cells can’t enter the control center unless they clear a careful screening process. Blood has to cross through a blood-brain barrier — the body’s equivalent of a metal detector.

Doctors and researchers believed this process kept larger cells from the immune system, which are too big and pack the kind of weapons the blood-brain barrier would filter out, from getting into the central nervous system.

The central nervous system has cells called microglia which are on active patrol, in much the same way as macrophages in the rest of the body. They are looking for potential problems that require immediate correction or attention.

In some neurological diseases, these microglia are especially prevalent and may exacerbate a problem. In other cases, however, a different type of microglia may help stabilize neurological function and signaling.

Stella Tsirka, a professor in the pharmacology department at Stony Brook University, has been studying these special cells to determine what roles they play in disease and in signaling between the immune system and the central nervous system.

Tsirka explained that her lab has divided their research into two areas. The first looks at the pathology of neuro-immune interactions. They are studying a model of stroke, multiple sclerosis and models of spinal cord injuries.

After an injury, “immune cells play an important role in maintaining or modifying the environment around the area of trauma,” she said.

The microglia are thought to be the first line of defense against injury. Later, additional peripheral immune cells infiltrate the central nervous system (when the normally secure blood-brain barrier is compromised) and modify or preserve the injured central nervous system.

At the same time, their more recent work studies the role of microglia to see how they function in the normal central nervous system (CNS).

“We’re trying to find out how neurons behave when there are microglia or not microglia present,” she offered.

Microglia may be something of a neurological stabilizer, she added, although it’s “not established yet.”

During development, microglia are thought to help in the maturation of the CNS by removing unwanted cells from neuronal terminals.

In the normal process of aging, microglia numbers increase, Tsirka observed. Exactly how they are involved in aging and potential neurological regulation with time isn’t clear yet.

Complicating matters further is that there are two different types of microglia: M1 and M2. They have opposite functions. M1 promote inflammation and cell death. M2 are anti-inflammatory and enhance cell repair and regeneration.

Treating microglia with a small beta peptide called Tuftsin has, during neuronal injury, fostered M2 properties. Using this in a model of multiple sclerosis resulted in a reduction in behavioral symptoms associated with multiple sclerosis.

So, if these microglia are relatively large and function like immune cells in the central nervous system, how did they pass through the security system that has such strict restrictions?

The key, Tsirka offered, is that they were in the pre-brain before the body constructed the security system. Indeed, a paper, which has not been verified yet, suggested that microglia migrated into the central nervous system from the human embryo’s yolk sac.
A resident of Setauket, Tsirka has worked at Stony Brook since 1992, when she came to do her postdoctoral research. She is married to Michael Frohman, the chairman of the pharmacology department. She does not report to her husband: she reports to the Dean of Research in the School of Medicine.

Their 18-year-old son Evan recently started college at Northwestern University, where he plans to blaze his own trail by studying mathematical models in social science. Their daughter Dafni, 15, entered Ward Melville in September.

Born and raised in Greece, Tsirka is the local president of the New York chapter of the American Foundation for Greek Language and Culture. Tsirka has supported the university’s efforts to build a Hellenic Studies minor and, eventually, a major.

Tsirka, who met her husband — who does not share her Greek heritage — when they lived in San Francisco, said she can relate to several elements of the movie “My Big Fat Greek Wedding.”

Despite the distance to her parents in Greece, they play an important role in her life. Every morning, she talks to them via Skype.

“If I’m not on by 7 am, my mom is worried something is wrong,” she laughed.
While her family tradition doesn’t include spraying Windex on everything (like the movie), she said family celebrations include food (although not lamb).

She also has been known around her lab for finding the Greek root of words and for sharing Greek expressions. One of her favorites: “It is not the sign of a wise man to commit the same sin twice.”

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