Like a pit orchestra hidden beneath the stage during a musical, a collection of often unheralded people work for years to make it possible for astronauts to dazzle the world with their journeys further from home than anyone has ever gone.

A physicist at the NASA Space Radiation Laboratory, Michael Sivertz is one of the researchers working behind the scenes to help make those majestic launches that carry astronauts deep into space safer.

Along with other physicists, biologists, and a host of others, Sivertz helps run, maintain and prepare the equipment NASA built in 2003 to test the effects of cosmic radiation on everything from different systems in the human body to the electronics that make space flight possible.

While he doesn’t test the cells themselves, Sivertz helps create and understand the kinds of radiation that enable other scientists to see how these DNA-altering and cell-altering ions might affect people who spend prolonged periods in space. He studies mitigation efforts that include shielding.

“When a proton goes through your DNA, it dislodges an occasional base pair,” Sivertz said. That’s like knocking a piece out of a jigsaw puzzle. The human body then looks for a part that fits in the empty space. “The repair happens trivially.”

When an ion of iron, however, goes through DNA, “it’s like a bomb going off. It quite frequently breaks both legs of DNA, and much damage is done. There is no simple recipe for putting those pieces of DNA back together in a foolproof way. That’s what makes space radiation so different,” he said. Sivertz’s role, he explained, is to develop the instrumentation that makes tests of cellular reactions to different kinds of radiation possible.

Peter Guida, a biologist at BNL who provides a similar expertise at using the NSRL, appreciates his colleague’s work. Sivertz “was chosen in particular because of his background, expertise and work ethic to become part of the NSRL program,” said Guida, who has known Sivertz for more than a decade. “That’s proven to be an extremely wise choice.”

Sivertz is working to understand the beam, its energy, its fragmentation, the way it loses energy and its stopping range — how far it goes through a material before it stops. He recently conducted a series of measurements to study the scattering cross section and charge-changing cross section for a variety of ions, including oxygen, carbon, and helium 3 and helium 4, which are isotopes of helium. “BNL is one of the only places in the world that can accelerate helium ions to produce an ion beam,” he said, while NSRL is the only facility designed to simulate the entire cosmic ray spectrum.

Sivertz also helps make it possible for scientists to test the effect of radiation on electronic devices. “As the characteristic size of electronic devices has shrunk, they have approached the size of cells, and their activation energies are similar to that of cells,” he explained. “Models for electronic behavior are sharing understanding with models for cellular behavior.”

Sivertz recognizes the need to understand how the environment in space might affect expensive systems. “If you’re going to send up a $1 billion satellite, you want to make sure some $5 memory chip doesn’t bring it down when it gets hit” by radiation, he said.

About a quarter of the time, Sivertz gets to pursue his own research, which includes a more precise understanding of the nature of the beams he’s directing toward test samples. Ion beams delivered at NSRL begin as a pure beam. As that beam moves through the air and equipment along the way, some of those ions hit atoms in the air, scatter or break into fragments, he described. For some experiments, researchers need to know exactly what happens to the beam and how it changes.

He is also working with people on helping to build better proton therapy treatment for cancer. Proton therapy may be more targeted toward tumors because the protons move at a slower speed, causing them to distribute all their energy at the site of a tumor rather than in healthy layers of tissue before and after the tumor.

Like members of a pit orchestra, Sivertz and Guida both play the same instrument: the guitar. Guida said Sivertz keeps his nylon-stringed guitar near the beam line, to strum some classical strains during the unusual moments when the beam line isn’t functioning.

In addition to being a talented scientist, Guida said, Sivertz is “a pretty good guitar player.”

Grigori Enikolopov — or Grisha to his colleagues — is involved in pushing limits. The associate professor at Cold Spring Harbor Laboratory and member of the graduate program at Stony Brook University is developing ways to refine state-of-the-art imaging to see the creation of new brain cells in adults.

The cells he’s seeking to observe are stem cells located primarily in the hippocampus. In animal models, these stem cells have the potential to restore memory after an injury or disease, enhance mood or improve the ability to learn.

“His latest work is very bold in trying to refine imaging” to be able to observe in real time “the generation of new brain cells,” said Dennis Steindler, the Joseph J. Bagnor/Shands Professor of Medical Research in the Department of Neurosurgery at the University of Florida. Steindler, who has known Enikolopov for over a decade, said his Cold Spring Harbor Laboratory colleague is “pushing the limitations of imaging. We’re at the point where we’re going to see what the resolution limit of noninvasive imaging of a brain is, anatomically and molecularly.”

Enikolopov and Steindler also led a study that will help prepare astronauts push the limits of space travel on potential future trips to Mars. The scientists explored the effects of cosmic radiation on these same important stem cells. They discovered that inactive stem cells are vulnerable to the effect of prolonged periods in space.

Working with Marcelo Vazquez at Brookhaven National Laboratory among others, the group discovered that these neural stem cells were sensitive to cosmic radiation. This finding, which was published in 2008, will help NASA with future missions that could involve prolonged exposure to cosmic radiation.

“Space travel in the future will use the data that [Enikolopov] and my collaborators helped develop to provide better protection methods for astronauts taking long space trips,” Steindler said. “It speaks to the breadth and scope of [Enikolopov’s] research” that he could become an instrumental part of this team.

Indeed, Enikolopov is interested in a broad range of areas related to stem cells, including understanding the signals that activate these powerful cells that can become neurons or glial cells, which are critical for the functioning of neurons in the brain.

Up until about 20 years ago, scientists didn’t even know stem cells were located in the hippocampus. Only recently were researchers like Enikolopov able to demonstrate the connection between stem cells and new neurons, learning, memory and mood.

“The idea that new neurons may be important for new memories was a natural and intuitive one, but it took a while to prove that,” Enikolopov said.

Steindler called Enikolopov “a rare scientist who has a grasp on many different complex technological approaches,” and said his Cold Spring Harbor collaborator has helped make important discoveries.

Enikolopov said stem cells are often involved in helping recover from damage to the brain. He and other scientists don’t yet know how these stem cells assess and repair the damage. As people age, the number of new neurons produced decreases, which means each of the stem cells adults have becomes more important at warding off age-related cognitive declines.

“Preventing the birth of new neurons from stem cells in the adult brain causes problems with memory; conversely, increasing production of new neurons enhances memory,” he said.

In animal models, running and living in an enriched environment increases production of new neurons. With humans, scientists still have to prove that, although Enikolopov believes that people should also benefit from exercise and experiencing new environments and ideas.

If Enikolopov and Steindler are effective, they may some day help “make 80 the new 40,” Steindler said.

While Steindler is an enthusiastic supporter and collaborator, he isn’t the first American scientist to appreciate the talents of the Russian-born Enikolopov. James Watson, the Nobel Prize-winning former director of CSHL, was visiting the institute in Moscow where Enikolopov worked. Watson invited him to become a visiting scientist at Cold Spring Harbor Laboratory.

Enikolopov understood his appointment would last around a year. “We thought this would be temporary” when he and his wife, Natalia Peunova, an independent research investigator at Cold Spring Harbor Laboratory, left Russia. That was a quarter of a century ago, as the couple raised three children on Long Island and have two grandchildren.

Enikolopov enjoys driving along the North Shore, where he marvels at the water views.

As for his work, Enikolopov is hoping to unlock the stem cell code. The primary focus is on “understanding how stem cells produce new neurons and how they talk to other types of stem cells,” he explained.

Israel Kleinberg believes he’s found a weapon that will help the teeth of a child for whom sweets are both a reward and an evening entitlement. The distinguished professor and director of the Division of Translational Oral Biology at Stony Brook has developed a way to tip the scales in favor of the healthy bacteria in the mouth, while making life harder for the bacteria that eats sugars and produces acids that wear away minerals on teeth.

Kleinberg, who has been at Stony Brook for 41 years and is the founding chairman of the Department of Oral Biology and Pathology, discovered that the amino acid arginine, which is present in saliva, reduces acid in the mouth.

At the same time, he searched for a way to rebuild the calcium lost from the acid-producing bacteria. He combined these two ingredients into a product called BasicBites that is available on the Internet.

With two of these small, square chews a day, children can use their body’s own good bacteria to win the battle for teeth health, Kleinberg said.

Mitchell Goldberg, president of Ortek Therapeutics, a Roslyn-based company that is marketing and selling these chews, described the product as “prebiotic,” because it neither kills bacteria like an antibiotic, nor introduces additional bacteria, like a probiotic.

Kleinberg has distinguished himself at Stony Brook in translational research, Maria Ryan, the chair of the Department of Oral Biology and Pathology said.

Indeed, when he first arrived at Stony Brook, Kleinberg worked with Sen. Ken LaValle to create the patent policies for the entire SUNY system, which would help in the discovery of therapies outside the realm of his own research, including Reopro and Xiaflex, according to Ryan, who has known Kleinberg for about three decades.

Earlier this summer in South Africa, Kleinberg received the International Association for Dental Research Distinguished Scientist Award in Research in Dental Caries.

“This is one of the highest honors bestowed by the association to stimulate and recognize outstanding and innovative achievements that have contributed to the basic understanding of the causes and/or prevention of dental caries, commonly known as decay or cavities,” said Ryan. The award is “well-deserved recognition of his work.”

As for his latest creation, Kleinberg, an 84-year-old professor who continues to work five days per week, said BasicBites raise the pH in the mouth. A higher pH is considered more basic, while a lower pH is acidic.

Kleinberg recommends eating these chews slowly and gently twice a day, once before bed and once after breakfast. He suggests spreading it around the teeth with the tongue to push it into areas where cavities might otherwise form. “We picked vulnerable times based on people’s habits, especially kids,” he said.

When people go to bed, their saliva production drops. With less saliva, the bacteria that are getting fed, especially after meals that include carbohydrates and often conclude with sugars, are the acid-producing ones.

The BasicBites, which are chocolate flavored even though they don’t contain actual chocolate, make it tough for the acid-producing bacteria to eat the food leftovers stuck to or around the teeth.

“It’ll give you an extra weapon and an easy thing for you to do,” Kleinberg said. The BasicBites “are part of a program we have where we’re tackling different microflora,” he said.

In the morning after breakfast, the BasicBites, which are manufactured in North Carolina, can help maintain a higher pH for several hours, which means children will only need two a day. If a child has too many of these teeth-protecting chews, Kleinberg said he or she may get diarrhea.

A resident of Smithtown, Kleinberg has been married for 59 years to Constance. The couple have four children and eight grandchildren. Kleinberg shows no signs of slowing down.

“When people know my age, they say, ‘Are you retired?’” Kleinberg laughs. He said he asks them what they do in retirement and they say they do what pleases them. “I happen to be doing stuff that I’m crazy about,” he said.

Kleinberg’s chairman Ryan described him as a “committed academician” who is “extremely productive with his ongoing research.”

Ryan said her 9-year-old son Peter is a big fan of BasicBites and their inventor. Her son “insists on stopping in to Dr. Kleinberg’s office to try his latest flavor of BasicBites.”

One of the leaders on a high-powered team, Joel Hurowitz recently helped win a $1.4 million bid to build something that will eventually take a one-way journey far from home. Their device will need to withstand temperatures as low as 200 degrees below Fahrenheit.

Hurowitz, a research associate professor at Stony Brook, and a team that includes members from Stony Brook and the Jet Propulsion Laboratory, are creating one of seven instruments that will journey aboard the Mars 2020 rover mission. The group beat out 57 other proposals to win a grant from the National Aeronautics and Space Administration to construct their Planetary Instrument for X-ray Lithochemistry, which will be bolted onto the turret at the end of the rover’s arm.

“The thing that we’re really excited about is that, for the first time, we can link the texture of a rock to its geochemistry,” said Hurowitz, who is the deputy principal investigator on the project.

Up to now, the equipment NASA has sent to Mars has analyzed rocks by looking at pieces in a 4- or 5-centimeter circle, which is about the size of the top of a soda can. Such a large field of view, even from an average distance of 140 million miles away, makes it difficult to determine “which ingredients go with which parts of the rock,” Hurowitz said.

Their new instrument will scan the rock in hundred micron steps, which is about the width of a human hair. This is also the size of clues at which small living organisms, or microbes, might leave their mark on rocks. This will allow for a more complete analysis of Martian rocks, helping NASA choose which rocks to bring back to Earth in the late 2020s.

The rock analysis will also likely give scientists a better understanding of the history of conditions on Mars over the last three or four billion years. Scientists generally believe that Mars had an early period ­— four billion years or so ago — when it had water on its surface, although some researchers believe that water was more like ice, while others suspect it may have had oceans, lakes and rivers.

Something changed dramatically, causing Mars to dry out, become nearly water free and get much colder. “While this big picture model is generally true, we’re finding deposits of water-born sediments in places that are younger than we might have predicted,” Hurowitz said, which is “out of sequence in general with this framework.”

When NASA sought designs for this instrument, Hurowitz and a team led by Abigail Allwood at Jet Propulsion Laboratory built two prototypes, one of which was used to gather data in the Pilbara region, which is in the northwestern part of Australia.

The Mars 2020 mission will include several other instruments, including: SHERLOC, which will seek evidence of organic compounds in rocks and soils, and MOXIE, which will attempt to produce oxygen from Martian carbon dioxide.

While Hurowitz is developing a device that will never return, he himself has come back to a place he called home when he was a graduate student in Stony Brook in Scott McLennan’s lab. After a seven year absence in which he worked at JPL, Hurowitz rejoined Stony Brook last year.

McLennan appreciates the talents of his former Ph.D. student. Hurowitz “has all the attributes of an outstanding scientist and educator,” McLennan said. He has “exceptional laboratory skills, having designed and built experimental labs at Stony Brook and JPL.” McLennan said Hurowitz is recognized in the field for research that combined lab and Mars mission data to gain a better understanding of how the surface of Mars weathered over geological time.

A professor in the Department of Geosciences, McLennan believes Hurowitz, who will become an assistant professor in a few weeks, is a considerable asset.

He “will create really unique and great opportunities for training Stony Brook graduate and undergraduate students to be the next generation of planetary scientists,” McLennan said.

Hurowitz and his wife Tanya, an assistant principal at an elementary school on the South Shore, recently bought a home in Stony Brook, where they plan to raise their two young sons.

As Hurowitz and Allwood prepared their NASA bid, Hurowitz felt that “this will all be worth it when we’re standing on a sunny beach in Florida, watching the rocket lift off with our families next to us and the instrument team beside us.”

When Justine Haupt was a teenager, her mother had a camera that wasn’t working. “I can fix it,” Justine said. Her mother, Lorraine Labate, who recently became a substitute teacher’s assistant for BOCES, was skeptical. “It doesn’t work anyway,” she urged. “Can I have it?” Her mother found that logic hard to refute, so she gave the camera she didn’t expect to work again to her daughter.

Haupt discovered an electrical problem that prevented the film-advance motor from functioning and fixed it. That early curiosity came in handy for Haupt, who started out as an intern five years ago and is now a design engineer in the Instrumentation Division at Brookhaven National Laboratory. She is working on a camera that will have the largest lens and the largest sensor/detector array ever built.

Haupt is a part of a team that is developing the Large Synoptic Survey Telescope, which will allow astronomers to study dark matter, dark energy and asteroids that threaten to collide with Earth.

The LSST is a long-term project that includes numerous scientists at BNL, as well as other parts of the world. Ultimately, the camera for the LSST, which will find a home in Cerro Pachon in Chile at 8,800 feet, is expected to open its shutters for the first time in 2019 and will start its scientific survey around 2022.

Haupt earned distinction for her work this year, as Mouser Electronics and Design News named her the 2014 Rising Engineering Star. “She is exceptional in her engineering talent,” said Paul O’Connor, who is the head of the Instrumentation Group. “She also has a lot of outside interests, which I thought would be appealing” to the magazine.

Those interests include serving as a director-at-large for the Custer Institute in Southold, which is the oldest public observatory on Long Island. Haupt “did a lot of work with the instrumentation there,” O’Connor said. Her background in optics has been “very helpful” to his department at BNL, O’Connor said.

Haupt works with software she taught herself to use that allows her to print out three-dimensional images of her designs, O’Connor said. She can start with a concept in the morning and provide a finished product by the end of the day and has kept the department’s two three dimensional printers “running practically 24/7,” he added.

Haupt is specifically involved with optical, mechanical and thermal design for testing and prototyping a raft tower module. When 21 of these RTMs come together, that will form the final sensor array in the camera ­— or, as she puts it, the film.

There are portions of this raft that require precise mechanical alignment to preserve the image quality. The entire object lives in a vacuum because the sensors require low temperatures. The electronics, however, generate heat, so the thermal and mechanics have to be stable for the digital film part of the telescope to function without wearing down. Haupt said anything that’s put in the vacuum with the sensors has to be cleaned meticulously and handled carefully.

While Haupt’s role is in the creation of the telescope, she, like O’Connor, plans to follow the discoveries this tool will enable scientists to make in the world of astronomy and physics. “That’s part of why I look forward to coming to work,” she said. “I’m working on the instrument that we think will lead to the discovery of the mystery of dark matter. I will definitely be watching it closely.”

A Rocky Point High School graduate and current Rocky Point resident, Haupt has not only spent time thinking about the stars and helping create an instrument that will enable their study, but has also logged hours closer to them than many of her neighbors on the land-locked Long Island.

Until the last few years, she owned a 1947 Stinson Voyager, a single engine plane. She worked on the avionics for the plane.

Haupt’s grandfather, Daniel Labate, was a welder and had a machine shop in his basement. When Haupt was 5 or 6, her grandfather taught her how to use a lathe. He also showed her how to solder and got her involved with model railroads.

After they saw her success with a camera, Haupt’s parents gave her electronics that were no longer functioning, like VCRs. “I built up a big camera collection,” she recalled.

Calling them as she sees them has stirred up some trouble for Heather Lynch. An ecologist at Stony Brook, Lynch recently shared her estimate of the global population of the Adelie penguin, which waddles, feeds, and raises its young in the Antarctic.

The Adelie – pronounced ah deli – are considerably more numerous than previous estimates. Considered an indicator of climate change in the Antarctic because they respond to local conditions around the colony, the two and a half foot flightless water fowl number about 3.79 million breeding pairs, which is 53% higher than earlier figures.

“The losses” in some penguin populations “are more than offset by the gains we’re picking up on the continental part,” Lynch said.

Lynch has received some frustrated emails from conservationists that suggest the results may not be consistent with the messages they are sending.

“Our willingness to report on these findings makes some conservationists uncomfortable because there is a tendency in the media and with readers to conflate population gains with a rejection of climate change, or even as a benefit of climate change,” she said. The evidence, and the use of that information, doesn’t invalidate the notion of global warming or make the penguin, an animated hero in movies and an attraction to families at the Central Park Zoo, any less important or worth studying.

“Climate change is occurring in Antarctica: the shifts we have documented in the Adelie populations speaks to the ecological changes now under way due to climate change,” she said.

Looking closely at the numbers, Lynch said the population of this type of penguin, which has a white ring around the eye, long black tail and white chest that gives the bird its tuxedo appearance, has decreased on the Antarctic peninsula, amid a reduction in the population of one of their primary food sources, krill, in the Western Antarctic Peninsula. Those declines, however, have been more than counterbalanced by greater penguin population on the continent, where these birds may have found more places to breed and where there has been a decline in the toothfish, a competitor that also eats krill.

Lynch said the study of the Adelie penguins is a “complex story” and will require further study to identify the causes of these changes.

Indeed, Lynch and her collaborator on the penguin population project, Michelle LaRue, a research associate at the University of Minnesota in the Earth Sciences Department, surveyed these birds to provide information that might help policy makers with fisheries management. They didn’t intend their study to ruffle feathers in the conservation community.

“Pinning down the distribution [of Adelie penguins] is one piece of a larger puzzle to determine sustainable krill catch limits,” Lynch said. LaRue and Lynch spent about 10 months pouring over satellite images. The satellites were not able to pick up the image of these waddling birds, but they were able to provide a map of their guano, or droppings. The color of their droppings is usually reddish.

Since this was the first time researchers used satellite images, the comparison to earlier data, providing the 53% increase, creates some room for interpretation.“We were using published information,” said LaRue, which included “the information on hand at the time,” but didn’t tap into the views afforded by satellite images.

Indeed, Lynch and LaRue plan to revisit this number in about five years, using the same method to compare the change in the number of penguins.

“We could have caught them on a high year,” LaRue said. “The next time, it could be lower or vice versa. This represents a base line from which we can make better and more accurate management decisions and learn about the species.”

Lynch and LaRue have collaborated for close to four years. Lynch is a “brilliant quantitative ecologist,” LaRue said. “When you’re in the field, you go, go, go.”

After a full day of trudging through three feet of snow to collect information about penguins, Lynch took more pictures of the colonies all the way up until the last call to return to the ship, LaRue described.

Lynch said she sees her role as providing data regardless of the result. “I want to be the trusted umpire,” she said. “I limit my comments to what the data are telling us.” At this point, she said, the data are telling her what is happening. The next step is to figure out why.

Molly Hammell had her head way beyond the clouds when she met Victor Ambros. At the time, she was a graduate student studying how models of dark matter and dark energy contribute to the distribution of galaxies seen in the sky. Through friends, she met Ambros and asked him about his work in molecular biology.

An amateur astronomer who took photographs of the night sky with a small telescope in his backyard, Ambros brought his family to public observations sessions Hammell ran at the Dartmouth College observatory. Speaking with Ambros helped give her the “biology bug,” she said.

Instead of looking at the remnants of dead stars like Cassiopeia A, which exploded around 1670, Hammell decided to focus her attention on events happening inside cells. Hammell handled the transition from astrophysics to biology incredibly well, said Ambros.

“In less than two years in my lab, [her] breadth and depth of biological knowledge had become comparable to that of any other postdoc at the same stage,” Ambros, the co-director of the RNA Therapeutics Institute at the University of Massachusetts Medical School, said.

She also shared her skill sets with the lab. Her lab meeting presentations were “exceptionally lucid and especially appreciated … as she could often make it almost effortless for the rest of us to understand what had been for us unfamiliar mathematical concepts,” Ambros said.

Now an assistant professor of genomics at Cold Spring Harbor Laboratory, Hammell studies transposons, or jumping genes. These bits of DNA can cut themselves out of one place in the genome and insert themselves into another spot. Another type of transposon makes an RNA copy of itself and then uses that copy to insert new DNA in another spot.

Transposons transcripts can become misregulated in neurodegenerative diseases, including amyotrophic lateral sclerosis, or Lou Gehrig’s disease, and frontotemporal lobar degeneration.

Her work with transposons has not only generated results, but has also distinguished her as a Rita Allen Scholar, an honor she received at the beginning of July. The award supports promising early career investigators and provides up to $110,000 annually for five years.

Hammell and her collaborators “have made one of the first connections between transposon activity and the function of a protein associated with neurodegenerative disease,” Ambros said.

“The possibility that transposon activation could contribute to the causes and/or progression of neurodegenerative disease is an extraordinarily important question.”

Hammell said she has looked for clues about the link between transposons and these diseases. It’s unclear yet whether the transposons are a causal factor in these diseases or whether they are a byproduct. Working with others at Cold Spring Harbor Laboratory, including Joshua Dubnau and Marja Timmermans, Hammell is hoping the team can gain a better understanding of the way transposons affect neurodegenerative diseases.

In one line of experiments, the researchers are looking to take animal models of these diseases and inhibit transposon activity. “If we can slow down or stop the symptoms in those models, that would be a fabulous clue,” she said.

Hammell is using computational analysis to differentiate between the effects of a protein called TDP-43 that is implicated in these diseases and the transposons themselves. Studies at Cold Spring Harbor Laboratory indicate that TDP-43 might normally keep transposons in check. If TDP-43, however, doesn’t work the way it should, these transposons can become more active, which may lead to diseases.

Some transposons, Hammell said, are closely related to retroviruses in the way they are copied in the cell. Drugs like AZT that is used as a treatment for AIDS might also be effective in controlling transposon activity in patients with ALS and other neurodegenerative diseases.

Hammell lives in lab-provided housing with her 10-year-old daughter Anna and her 4-year-old son Max in a converted firehouse on the shores of the harbor. The previous exit door for fire engines is now a huge glass window overlooking Cold Spring Harbor.

As for her work, Hammell appreciates the opportunity to contribute to research that may help people suffering with disease. Hammell’s grandmother succumbed to Alzheimer’s disease when she was a postdoctoral student. “If the work I do helps understand the progression of that disease,” she said, “that would make my family proud.”

Ralph James has surpassed Derek Jeter. Working with a team of scientists at Brookhaven National Laboratory, James, a prolific scientific innovator, has now won the prestigious R and D 100 Award, described as the “Oscars of Invention,” six times, topping the retiring Yankee shortstop’s five World Series rings.

James, who is a senior scientist and group leader in the Nonproliferation and National Security Department at BNL, has led a group that has developed and improved a wide range of technologies that have applications in everything from detecting signature radiation from weapons to finding more efficient ways to detect tumors inside the human body.

The R and D 100 Awards have been given out annually by R and D magazine since the 1960s and include inventions like the halogen lamp and HDTV. James credited colleagues, including Aleksey Bolotnikov, with collaborating to produce the latest award.
BNL and James’ department have benefited from the scientist’s awards and from his vision for a department that has been able to recruit talented scientists.

“James creates conditions where we can attract the best people from all over the world,” said Bolotnikov, who is originally from Russia and who has colleagues from China and India. “All these awards convince our sponsors that we propose good ideas.”

Bolotnikov called James “visionary,” “an expert manager” and a “supporter of good ideas.” Bolotnikov, who shared in three of the R and D 100 awards, said he is “glad [James] directed me in the right direction.”

The latest award involves improving the performance of detectors produced from lower-quality and cheaper crystals, making them more effective at looking for the signature of a particular kind of radiation.

James helped develop cadmium zinc telluride, or CZT, crystals, which enable scientists, medical researchers, and homeland security experts to collect information about a radiation source at room temperature.

Prior to the creation of CZT, scientists used germanium to detect radiation. The biggest problem with germanium, which is, as James said, “the most pure material that exists today,” is that it had to be cooled to minus 200 degrees Celsius or minus 328 degrees Fahrenheit. These germanium detectors, which are still used in some places today, needed several hours to cool down and required considerable maintenance.

The discovery of CZT, however, enabled technicians to get specific isotope information at room temperature. Isotopes are variations of the same element with different number of neutrons. Uranium, for example, has several isotopes, including the more common Uranium 238. The lighter U 235, which occurs in natural uranium but at a very low concentration, however, can be used in nuclear reactions when it is enriched and is an isotope officials from Homeland Security, among other organizations, monitor closely.

Early in his career, Zach Foda, who graduated from Ward Melville High School in 2005, has done something his father, Hussein Foda, an award-winning pulmonologist and medical researcher, hasn’t accomplished in a medical and research career that spans over three decades.

An M.D.-Ph.D. candidate at Stony Brook, the younger Foda recently participated in a research project on diabetes that was published in the prestigious journal Nature. The study, led by David Liu, a Harvard professor of chemistry and chemical biology, found a new possible treatment approach for diabetes, inhibiting something called the insulin-degrading enzyme.

“The Journal Nature is one of the very highest-impact journals in the country and actually in the world,” said the pulmonologist father, who is a professor of medicine in the pulmonology critical care division at Stony Brook. Everything after this, he laughed, may be “downhill.” As a member of Markus Seeliger’s lab in the Department of Pharmacology, Zach Foda helped determine the three-dimensional structure of the inhibitor compound and showed how it was bound to the insulin-degrading enzyme.

Over 20 million people in the United States live with type II diabetes, a problem in which the body can’t make enough of the hormone insulin. The IDE removes insulin from the blood. People with diabetes typically inject insulin, take medicine to increase their sensitivity to the hormone or take other drugs to increase the insulin their bodies produce. Inhibiting the effect of this enzyme may enable insulin to remain active in the blood for a longer time.

Testing their compound in mice, Liu and his Harvard colleagues showed that the inhibitor increased insulin levels, which in turn lowered blood sugar. While this study is encouraging, scientists caution it could be some time before this approach goes through all of the screening steps to become an approved treatment for diabetes.

Seeliger and Foda became involved in this collaboration at the request of Liu. An expert in determining the structure of molecules, Seeliger studies the structure of inhibitors of enzymes called protein kinases, some of which are involved in cancer.

When Liu reached out to Seeliger in the fall of 2011, the Stony Brook researcher didn’t hesitate to join the latest collaboration. Liu is “a total rock star in the field,” Seeliger offered. “I was delighted when he contacted me out of the blue initially. It was a no-brainer to say, ‘Sure, we’d be interested.’” Liu praised his Stony Brook collaborator. Seeliger is “a highly talented, dedicated and scholarly biochemist and structural biologist,” Liu offered in an email. “He is a superb collaborator and an asset to our community.”

While Seeliger contributed an important element to the diabetes study, he focuses more of his work on other areas, including studying the structural nature of kinases and the drugs used to affect them. Kinases are “important drug targets,” Seeliger said.

“There are a lot of potential compounds out there that could become drugs for kinases, but most of them don’t work well enough. We want to help understand why they don’t work.”

Kinases are signaling molecules inside the cell. If they send an incorrect signal, a cell could die or develop cancer, Seeliger explained. The problem in targeting these kinases is that there are many similar signaling molecules and it’s “difficult to turn off one without turning another one off. We need a high specificity of kinase inhibitors.”

The “Holy Grail” for Seeliger in his research would be to find out how a drug binds to a receptor, and not just what the final configuration of the drug and the receptor are. Seeliger, who considers himself a visual person, said he is humbled by people who bake professionally. Being able to manipulate yeast, flour and other ingredients to create a moist and spongy bread is something that “impresses me.”

Seeliger, who lives in Stony Brook, is married to Jessica Seeliger, an assistant professor who is also in the pharmacology department at Stony Brook. The couple enjoy going to the beach and visiting Stony Brook Village. Seeliger is a scuba diver who has explored the waters around Long Island.

Seeliger credits Foda with doing much of the hands-on and computational work on the structural part of the diabetes study.

Foda recently married equine veterinarian Kiara Barr and is going back and forth between Long Island and Westchester, where his wife will work with and show horses until she moves to the University of Pennsylvania next year.

The elder Foda said he is “very excited” for his son’s early success and, as someone who chose to combine medicine and research, is also pleased with his son’s career choice. “I’m very proud of him.”

Life depends on taking a set of instructions and copying them over and over. That’s how the code that builds everything from aardvarks to kangaroos to zebras works. Inside each cell, a set of blueprints provides a twisting, ladder-like key that enables plants, animals and yeast to survive, grow and produce the next generation.

While the way that code is copied in creatures like bacteria is well known, the key structural changes that lead from the beginning of the copying process to a full-fledged new set of instructions for so-called eukaryotic organisms, or those with a true nucleus, remains a mystery for organisms like fruit flies, elephants, kangaroos and humans.

“In eukaryotes, the machine performs a similar function” as it does for bacteria, said Huilin Li, a biophysicist at Brookhaven National Laboratory and a professor of biochemistry and cell biology at Stony Brook, “but it’s more complicated. When it’s larger, it’s difficult to deal with and it’s difficult to study its structure.”

The concept of replication, or copying, is known. Li is studying the steps to get from the beginning of a copy to another model with the same important genetic information embedded in it. “Life has evolved this powerful copy machine and we want to know how the copy machine is assembled from scratch and how it works,” said Li.

Li likens his work to studying a car. “If you never saw a car and you suddenly see it running, you would wonder how it can move,” he said. Many of the protein complexes he studies can literally be called nanomachines, he said. Seeing the structure will help determine the function, he said. Quoting Albert Einstein, Li said, “If I can’t picture it, I can’t understand it.”

Li uses an electron microscope to magnify these parts up to a few million times. When he takes a picture, he explained, he controls the number of electrons to keep what he is looking at intact. Because he can’t use that many electrons, however, the picture is not fully exposed, leaving the image blurry or noisy. He takes many of these pictures and uses a computer to average them to get a sharper image.

Li’s work with electron microscopy has “definitely made a splash,” said Christian Speck, a nonclinical lecturer in the Faculty of Medicine at the Institute of Clinical Science at the Imperial College in London, who has collaborated with Li for over a decade. “I still remember when we saw the first structure of a large replication complex in 2004, we all realized that [Li’s] approach was a game changer. We had to think about DNA replication from a completely different perspective, as we could see for the first time the proteins that we have been working on for such a long time.”

Over the years, Li has determined the structure of a genetic machine called the Origin Recognition Complex. The ORC, which is comprised of six proteins, finds the special stretches of DNA, called replication origins, in the sea of a genome. Like a car that consumes gas, the ORC burns a form of chemical energy called adenosine triphosphate.
The ORC recruits a secondary machine, called a helicase, that splits up the DNA. “We recently captured a picture of the recruitment process,” said Li.

Working with Speck, who was at Cold Spring Harbor Laboratory when he started collaborating with Li, the tandem figured out the structure of this 14-protein, two-machine system. When these machines aren’t closely regulated, they can overduplicate DNA, leading to uncontrolled cell growth and proliferation. “A hallmark of cancer is the regulation of replication,” Li said. “They don’t stop replicating” when normal cells would.

Li is also trying to understand how a protein machine called proteasome helps the tuberculosis-causing bacterium, Mycobacterium tuberculosis, survive inside the host immune system.

Li and his wife, Hong Wang, who works in the microbiology and immunology department at Stony Brook, live in Miller Place. They have two sons, Paul, who finished his first year at the University of Miami and Calvin, who just completed his junior year at Miller Place High School.

Li grew up in China and came to the United States in 1994. He enjoys walking in the Pine Barrens at the Rocky Point Preserve.

In his approach to his work, he has a “deep appreciation of what’s under the surface,” he said. “As a scientist, part of the job is learning and, for that, it is really a privilege.”