Authors Posts by Daniel Dunaief

Daniel Dunaief

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Usually kept in check by the body, C. albicans can cause damage for those who are immunosuppressed

This is the second in a two-part series that began last week on two scientists at Stony Brook Medical School who are working to unlock the secrets of different types of fungi that can cause significant health problems.

Like the cracks in the sidewalk that we don’t notice most of the time, Candida albicans is everywhere. Mostly, though, it’s on and around us. While this fungus is harmless much of the time, it has a dark side.

After prolonged catheterization (tubes entering the body) or in people with weakened immune systems, Candida can enter the bloodstream, where it can cause significant damage.

“It’s considered to be the fourth most commonly acquired hospital infection,” explained James Konopka, a professor in molecular genetics and microbiology at Stony Brook Medical School. It often targets the kidney. Even with current state-of-the-art antifungal drugs, Candida can become life threatening.

In most people, Candida often can’t get past the skin or the lining of the gastrointestinal tract. That, however, changes when, for example, patients have surgical procedures.

“A tube going into a patient can provide a site for a biofilm and can get it across the skin,” Konopka explained.

This can also be compounded, he explained, by the use of antibacterial drugs, which eliminate the bacteria and give the fungus more room to grow.

Patients with weakened immune systems, through AIDS, cancer treatments or immunosuppressive therapies, can also be the target of fungal infections.

Konopka is looking from the outside of Candida in, trying to alter the cell wall, or plasma membrane. Everything in the membrane is not randomly moving around, he explained. There are specialized sensors that can be instrumental in its life cycle.

He’s been studying genes that are responsible for 30 proteins in the membrane. He has deleted the genes for most of these proteins and plans to pick the best candidates for more study and drug development.

“If we disrupt the function of those proteins, that leads to a global defect in how the membrane is organized,” he said.

One of the challenges in fungal research is that humans and fungi are more closely related, evolutionarily, than humans and bacteria. On the positive side, that means research into basic cellular mechanisms of fungi may provide information about human cells.

On the downside, however, it provides a tricky type of Venn diagram for medical treatment. Doctors and researchers have to find drugs that only affect fungi and that don’t harm human cells at the same time.

The existing therapies have limitations. As with bacteria, some fungal strains have developed resistance.

Even finding a specific therapy that targets and eliminates Candida could lead to another unintended consequence. Because Candida lives within most of us without causing problems, eliminating all of the fungus could create an opening for an infection from another type of bacteria or fungus.

“There’s been some suggestion that that possibility may be occurring in certain patients in long-term drug therapy,” Konopka acknowledged.

He’s not convinced that’s the case, but it has caused some researchers to think Candida might be filling a niche that keeps worse invaders out.

The ideal therapy may involve a short-term treatment that clears Candida from internal organs, but resets the relationship to where the fungus lives within humans without doing any damage.

At the University of Washington in Seattle, Konopka had been doing basic fungal research under the guidance of Leland Hartwell, who shared the Nobel Prize in 2001 for discovering protein molecules that control the division of cells. When Konopka moved to Stony Brook, he transitioned to studying Candida.

In 2008, he discovered that deleting the proteins in the plasma membranes caused the cell wall to grow backwards.

“There’s a layer of regulation that keeps the cell wall on the inside,” he explained.

Konopka lives in East Setauket with his life, Susan Watanabe, a scientist who is studying HIV, the virus that causes AIDS.

He said he wades out into the water at West Meadow Beach, where he catches bluefish and striped bass.

As for working with fungus, there is an upside: yeast. In the fall, he hosts an Oktoberfest party for his entire building, where he and his guests sample each other’s home-brewed beer. Last fall, the offerings included Strong Island Ale, Rye Smile and Midnight Spice. Konopka provided Hoppy Oktoberfest, a beer he describes as a “classic,” which has “the taste of fresh grown hops, but brings with it a fair amount of sweetness.”

 

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Long term goal is to find drugs that help immunocompromised individuals fight fungal diseases

One of them brews beer, while the other makes his own pizza. While it sounds like a great mealtime combination, what Maurizio Del Poeta and James Konopka do when they’re at work may one day help you or your friends and family.

The two are scientists at Stony Brook Medical School who are working to unlock the secrets of different types of fungi that can cause significant health problems. Del Poeta is studying Cryptococcus neoformans, a fungus that can kill if it reaches the brain, while Konopka is  working with Candida albicans, a fungus that normally lives with and on us but that can also do damage to internal organs, particularly the kidney.

Del Poeta, the pizza maker, has found a drug that targets a sphingolipid on the surface of Cryptococcus that clears the infection in the brains of mice. He recently applied to start testing that drug on humans. That process could take five years.

Konopka, the beer brewer, is targeting a 30-protein sequence in the cell wall of Candida. He is narrowing down the list of targets and hopes to start searching for effective drugs or therapies.

“These two men are superb,” said Jorge Benach, the chairman of the Department of Molecular Genetics and Microbiology. “They are sought after internationally and nationally” to address scientific audiences.

The Molecular Genetics and Microbiology department includes researchers who study viruses, bacteria and fungi. Benach said they are all aware of the potential medical benefit, even as they perform basic research to understand the way these pathogens work.

“It takes a while from what we do to the point where we can save lives,” he offered. “We are on that track. If you hit the ground running, you shorten that distance.”

The Times Beacon Record will profile the research of Konopka and Del Poeta in a two-part series. The Del Poeta feature will run today, while the Konopka story will run next week.

 

Maurizio Del Poeta loves stories. There’s the one about how he met his Italian wife when they were at Duke University. They were, he said with a laugh, two of the only three people originally from Italy at Duke.

He met her at a dinner party after he returned from a ski trip. The only complication: she was dating someone else.

“I was waiting for her to drop this guy,” he laughed. “He wasn’t good for her.”

Six months later, she became single and Del Poeta’s wait was over.

An avid reader, Del Poeta also has a story for a key insight into his research. While reading the late Michael Crichton’s anti-climate change novel “State of Fear,” an ironic choice given his findings, Del Poeta decided he had to test a fungus in a higher carbon dioxide environment, like that in the lung.

He was working with Cryptococcus neoformans, a fungus that is especially problematic in people who are immunocompromised — either through cancer treatments, drugs that suppress the immune system after organ transplants or in people with AIDS.

In the outside environment, a mutant type of this fungus grew normally, but “when you transfer it into the lung, it can’t grow anymore,” he explained.

When he studied it more closely, he found that a specific sphingolipid attached to the surface of the fungus in the mutant prevents it from growing in an environment that has 5 percent carbon dioxide (the concentration in the lung), compared with the approximately 0.4 percent in the atmosphere.

This sphingolipid and the genes and enzymes that lead to its production became a “fantastic target for developing drugs,” Del Poeta offered.

That discovery came in 2005. Del Poeta has spent the last seven years, including the last six months as a professor in the school of medicine at Stony Brook Medical School, looking for drugs that might target that sphingolipid.

He has found several that have worked. The survival rate of animals treated with these targeted drugs is 90 percent, compared with a 100 percent mortality rate when untreated.

Del Poeta submitted a grant to the National Institutes of Health for one of the drugs in February. It received a high score, he said, but it was not funded. After he conducted the promising mouse experiments this year, he resubmitted that grant in the middle of December. He hopes to hear back in the next few months.

The drug not only prevents the spread of an infection in the animal models but it clears the fungus from the brain. Currently in humans, there are no drugs that effectively eradicate the fungus in the brain.

Del Poeta said it may take five years before the drug goes through clinical testing to reach the pharmaceutical shelves.

While the drug is not toxic in animals, it’s unclear what reactions humans might have to it.

Del Poeta got involved in fungal research when he was a medical doctor at Duke. He observed that the patients he had who were immunocompromised, mostly because of AIDS, were dying because of this fungal infection.

He needed “to do something.” He consulted with his mentor John Perfect, who is now the director of the Division of Infectious Diseases at Duke, who suggested he choose between seeing patients and conducting research.

While he misses seeing patients, he finds his research satisfying, especially because of its potential practical impact.

In his research, he combines basic science with the search for drugs.

He explores the mechanism by which the sphingolipid limits the growth of the fungus. He is also looking at ways to boost other parts of the immune system that are not often weakened, even in immunocompromised individuals. He would like to raise the activity level of macrophages, neutrophils and Natural Killer (NK) cells.

A temporary resident of Port Jefferson, Del Poeta and his wife Chiara Luberto, who is studying leukemia at the cancer center at Stony Brook, recently bought a house in Mount Sinai. The couple have two young sons, Matteo and Francesco.

Del Poeta combined his passion for cooking and sharing amusing anecdotes in a cookbook called “Pasta con Amici.”

When he moved to South Carolina (a stop he made before landing at Stony Brook), he missed pizza so much that he built a brick oven with his father. He plans to build another one here, perhaps in 2013.

“I love stories,” he explained. “Behind a story, there is everything. Each of us has a fantastic story.”

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Physical factors, such as exercise and even vibrating platforms may have profound health benefits

One way to shake up an immune system may be, in fact, to shake up the immune system.

Clinton Rubin, the chairman of the Department of Biomedical Engineering at Stony Brook, has been studying the effects of low intensity vibrations as substitutes for physical activity on bone growth in animal models. He’s found, for example, that older sheep standing on a platform that’s vibrating at a level that’s barely noticeable show bone growth.

His latest finding is that these same slightly moving platforms can also raise the level of immune cells, including T cell and B cell levels, in an obese mouse.

While it’s early to extend this to humans, the findings present the possibility that these small vibrations may help contain or even prevent significant health problems that often threaten or damage the lives of people who are significantly overweight.

“Obesity makes you susceptible to a number of disorders,” explained Rubin, who is also the director at the Center for Biotechnology. “We hope that some day, if we are able to extrapolate these findings in mice to people, that these low magnitude mechanical signals can help mitigate the health complications that arise in those that are obese.”

Rubin cautioned that these signals would not be a substitute for a healthy diet, exercise and active interaction with a physician’s advice.

Ever since he arrived at Stony Brook University in 1987, Rubin has been studying how physical factors influence the musculoskeletal system, to understand, for example, how exercise can generate a profound health benefit. He has also looked at how the removal of these physical factors, through bed rest, extended time in space, and spinal cord injuries, can affect these systems. These low intensity vibrations have served as surrogates for typical mechanical loading signals.

Recently, he has studied the effects of these small vibrations on mesenchymal stem cells (or MSC). These cells can become bone cells, cartilage or fat cells. Low intensity vibrations for as little as 10 minutes a day can bias these cells away from becoming fat cells.

Rubin suggests the process may involve a signaling pathway that mimics the way muscles move bones. Muscles are generally inefficient motors, shaking as they contract (as anyone who has challenged themselves to do a few extra push ups or do a few more reps with weights can attest). The vibrations from these plates may provide a substitute signal for the muscle vibrations.

Rubin is the chief scientific advisor for a company called Marodyne Medical, which hopes to translate his science into a medical device that can address such problems as bone wasting, muscle wasting, obesity and diabetes.

Rubin readily recognizes he has a potential conflict of interest because of his involvement with a company he hopes will one day sell a product that could offer a nonpharmaceutical alternative for people with various bone or muscle challenges.

“Do I look at this stuff with rose-colored glasses?” he asked. “As a scientist, I hope not. I try to insulate myself as much as possible from the subjects in evaluating the data.”

Rubin said the university helps him address these concerns by ensuring he provides full disclosure, in publications, grants and lectures and by informing any human subject who participates in his studies of his dual roles.

He does not interact with potential subjects in his studies and all his scientific methods are performed in a double blind fashion. That means he doesn’t know which animal received which treatment when he records results.

As for the immune system response, the benefit from these low intensity vibration is through another class of cells, called the hematopoietic stem cells (HSC).

“If these bone marrow are influenced by mechanical signals, why not HSCs?” Rubin reasoned.

Rubin and his wife, Jennifer Sigler, live in Port Jefferson with their 16-year-old son Jasper. Sigler works as an architect for the building department in their village. Jasper, meanwhile, has kept his own musculoskeletal system active by playing right defensive back for the Port Jefferson Royals, who have won back-to-back New York state class C soccer championships.

Rubin, who has been at Stony Brook since 1987, said he struggles on the Port Jefferson golf courses, but that hasn’t kept him from the links.

Rubin appreciates the support and talent of his colleagues at Stony Brook, including Assistant Professor Meilin Ete Chang and senior doctoral students Danielle Green and Ben Adler.

His work, he said, suggests that even supporting weight can send the right signals to their bodies.

“When people ask me what they should do if they can’t run or walk, I tell them stand up,” he offered.

 

Cast call

Cast is sought by Star Playhouse, Suffolk Y JCC, 74 Hauppauge Road, Commack for their upcoming play, “Dirty Rotten Scoundrels.” All roles are open; ages 17 and up. Prepare to sing 32 bars of contemporary theater music. Bring sheet music in the proper key and be prepared for dance audition. Call 462-9800, ext. 136, or go to starplayhouse.com for further information.

Free Irish language classes

The Gerry Tobin Irish Language School will be offering free Irish language classes beginning on Wednesday, Feb. 6, at the Ancient Order of Hibernians Hall, 27 Locust Ave., Babylon. Classes include “Mommy, Daddy and Me,” for young children and their parents. Classes for new and advanced students are also available. Call 521-1227 or go to www.scoilgaeilge.org for further information.

Seamanship course

The U.S. Coast Guard Auxiliary Flotilla 2204 will be offering a boating and seamanship course beginning on Thursday, Feb. 7, at 7 pm. Classes will be held at the Smithtown Library, 1 North Country Road, Smithtown, and runs for seven sessions.

Upon completion of the course a certificate will be awarded, satisfying the Suffolk County boaters requirements and the New York PWC operators certificate; this also covers the young boaters requirements for those under 18 years of age. Additionally, boat owners may be eligible for an insurance discount.

The course is free; there is a nominal charge for course materials. Family participation is encouraged. Call 732-3562 for further information and to register.

Pysanky Easter egg workshop

The third annual traditional Ukrainian Easter Egg (Pysanky) decorating workshop will be held on Sundays, March 10 and 17, at the Resurrection Byzantine Catholic Church, Edgewater and Mayflower avenues, Smithtown. All levels of experience are welcome. Cost of the class is $20; each participant must bring a candle in holder, pencils and roll of paper towels. Registration is required by Feb. 8. Call 246-5669.

 

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Long Baseline Neutrino Experiment seeks to understand why matter triumphed over antimatter

If two armies of twins fought against each other with identical protective gear and equally fatal weapons, the result would likely be fatal for every one of them. At least, that’s how particle physicists see it when they look at the early universe.

The twins in the primordial battle are matter and antimatter. Matter includes positively charged protons and negatively charged electrons (which are also called baryons). The antimatter equivalent are negatively charged protons and positively charged electrons.

Somehow, when these two armies mixed in something akin to a soup, matter wiped out its antimatter counterpart.

But why, physicists wonder, did matter win? Could the battle, which physicists believe lasted mere microseconds, have ended the other way, or could the two sides have left nothing behind?

Physicists, including Milind Diwan of Brookhaven National Laboratory, believe neutrinos may provide the answer. Almost as plentiful in the universe as particles of light, neutrinos are so small that a trillion of them pass through our bodies each second. Not only are they harmless, they barely interact with anything else, because, while they do have mass, they are spectacularly small.

The sun, stars and even the Earth produce them and, thanks to particle accelerators, humans can, too. Diwan is part of a collaboration of 350 scientists, mostly from American universities, who are teaming up in a program called the Long Baseline Neutrino Experiment (LBNE) to use these nearly massless particles to try to understand the early triumph of matter over antimatter.

In the LBNE, the scientists hope to shoot neutrinos and antineutrinos 800 miles through the Earth — the experiment wouldn’t require any tunnels — from the Fermilab accelerator outside of Chicago to a research facility in a former gold mine, now called the Sanford Underground Research Facility in Lead, South Dakota.

The effort suffered a funding setback this past summer, when the Department of Energy praised the goals but asked the scientists to return with a plan that was affordable. The LBNE researchers broke the project up in phases. After the LBNE team made the suggested revisions, they received approval in early December from the DOE.

Diwan and his colleagues anticipate that the LBNE will provide evidence of how matter and antimatter behave differently as neutrinos make the long journey underground to a receptor in what was once the Homestake Mine, which was, up until it closed in 2002, the largest and deepest gold mine in North America.

Neutrinos have three different types, changing readily from muon to tau to electron. It is over these distances that these oscillations, as the changes are called, may help unlock the key to the asymmetry between matter and antimatter.

“If you measure their properties in this far-away detector, there will be differences,” Diwan predicts. “I suspect those differences will be quite large and … can be directly linked to the way the universe evolved in its first few microseconds” when antimatter was annihilated.

“We have been struggling to understand this miraculous event,” Diwan explained. “This is one of the key problems in all of science.”

While scientists plan to send the neutrinos on a long journey through the Earth, the researchers themselves are expecting their own long trek.

Based on the current plan, the LBNE will start producing data in 2022. By then, would-be scientists who are planning to graduate from high school this year may contribute to the research.

While that might seem like a slow build for a long range project, there are competitive time pressures.

“Japanese physicists want to perform a similar experiment with a shorter distance and Europeans want to perform a bigger experiment with almost the same experimental features,” Diwan explained. “At this point, there is agreement that in terms of planning, we are ahead of them.”

A resident of Port Jefferson Station, Diwan and his wife Sucheta, an engineer at Hauppauge-based Parker Hannifin, have a 14-year old daughter, Renuka, and a 10-year old son, Yashodhan.

His wife’s job is “much more important than mine,” he offers. Her company makes fuel gauges for jumbo jets.

As for his work, Diwan has been in the physics department at BNL since 1994. He is eager to see the LBNE project through.

“I feel very fortunate that I am working on a question that is important,” he offered. “It is extraordinary that we have the tools to actually perform this experiment.”

 

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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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