Authors Posts by Daniel Dunaief

Daniel Dunaief

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Imagine a pizza restaurant. Every day, the chef cooks a certain number of pies. At a specific point, the kitchen reaches a maximum. What if that restaurant could double its production?

That’s what Zachary Lippman, an associate professor at Cold Spring Harbor Laboratory, and colleagues in Israel did, except that instead of doubling his pizzas, he doubled the amount of fruit his tomato plants produced.

Lippman used the same kind of mutations that agriculturalists have employed for centuries to increase crop yields.

“The approach we took was to find new mutations and design specific screens” that would favor flowering instead of bushiness, Lippman said.

Lippman and collaborators from Israel created a tool kit of genes that balance between the hormones florigen and anti-florigen. The first one, florigen, promotes flowering and flower and fruit production. The second one, anti-florigen, promotes shoot and leaf production.

Florigen and anti-florigen are “like this yin and yang,” Lippman said. “We found mutations in genes that affect the florigen/anti-florigen paradigm.”

By cross breeding these mutations, Lippman and his associates were able to pinpoint what he described as “an optimal architecture,” which originates from an optimal balance of flowering signals, he said.

This genetic tool kit could have applications to other agricultural crops, such as soybeans, which, Lippman explained, share many growth similarities to tomatoes.

With the world population expected to reach 9 billion by the middle of this century, these kinds of discoveries could prove important in increasing food production, Lippman said. He is thinking of testing this tool kit in cowpea, a major crop related to soybean that is grown in Africa.

“The major advance in the present work is the illustration that fine tuning of signals from these hormones can help improve tomato field performance and thus, similar, directed changes can be applied in other plants,” explained Yuval Eshed a professor in the Department of Plant and Environmental Sciences at the Weizmann Institute of Science in Israel who collaborated with Lippman on this study. Eshed has worked with Lippman for almost a decade and called his partner “an outstanding scientist” who is “original, thorough and trustable.”

The approach Lippman and his team took does not involve inserting DNA into the plant but rather comes from the development of mutations, Lippman said.

“It’s the standard idea of classic genetic modification,” Lippman said. “We were able to design a way to find and select for mutations much faster than what Mother Nature has given us by using what people have been doing for decades.”

The genetic tool kit, with several specific mutations, gives scientists and, potentially, tomato producers a chance to boost the production without compromising the plant or the taste of the tomato.

At the same time there is no difference in the fruit quality or the plant, he said. “Sugar is unaffected,” he offered.

To be sure, like some animals bred in a zoo or plants farmers have used for hundreds or even thousands of years, these new tomato plants, with their collection of mutations designed to increase yield, would not fair as well outside of the confines of a farm. “What’s optimal in nature is not what’s optimal in agriculture,” Lippman explained. “We’re selecting for growing in greenhouses or fields.”

Lippman used this tool kit in cherry, plum and beefsteak tomatoes. He is hoping to test all major varieties of tomato, including slicing tomatoes for burgers, grape tomatoes and cocktails. This approach should work across the types of tomatoes, but he hasn’t conducted those tests yet. He has had some contact from companies that grow tomatoes and will likely enter a collaboration soon.

Lippman said introducing these new mutations into the elite breeding lines of tomato farmers may create some complications. “We don’t know how those mutations will respond” in the designer tomatoes agricultural companies use, he said. “One combination might work in one variety, whereas another combination might work in another variety.” The tool kit, however, provides a genetic resource.

“This summer, we repeated the experiment for a fourth time,” he said. He organized these plants in a row according to their mutations. “If you walk down the row, you could see the progressive quantitative increase,” with the plants going from bushy to less bushy to almost a tree. To see the yield [change] was even more impressive.”

Lippman, who has been working for for six years at CSHL, said these results are “by far the most important work to come out of my lab. This is the most fun” he’s had conducting research.

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This group will not let pain or loss defeat them. Instead, they are banding together to fight a common enemy.

Several foundations, the Friends of T.J. Foundation, the Christina Renna Foundation, the Michelle Paternoster Foundation for Sarcoma Research and the Clark Gillies Foundation, are contributing about $300,000 to fund research into a rare form of deadly pediatric cancer called rhabdomyosarcoma. RMS is a tumor of the connective tissue that typically involves muscle cells attached to bones.

The groups are backing a research partnership between Cold Spring Harbor Laboratory Assistant Professor Chris Vakoc and Charles Keller, the scientific director at the Children’s Cancer Therapy Development Institute, Fort Collins, Colo., to find a cure for a disease that afflicts adults and children equally. For children who get cancer, it is the most common soft tissue cancer.

The directors from these groups got together at a special Banbury conference of world leaders in RMS in May and pooled their resources.

The foundations “all gelled,” said Phil Renna, the director of operations for public affairs at CSHL and the co-founder of the Christina Renna Foundation. Renna’s foundation is named after his daughter, who died in 2007, a year after her diagnosis. Renna is “happy to say that we are able to put together” this research focus.

Vakoc and Keller have “hit it off” after CSHL president and CEO Bruce Stillman helped form the collaboration, Vakoc said. The research team hopes to “leverage what my lab does with epigenetics with [Keller’s] expertise in the clinical realm.”

Vakoc said his lab is invested in the discovery of cancer drug targets. He asks “cancer cells what they need to grow,” while they also explore what makes cancer cells different from normal cells.

Working on leukemia, Vakoc has already found a drug target, called Brd4. He plans to take a similar approach to RMS.

Vakoc explained that his lab uses a technique called RNA interference, in which he methodically searches for protein targets. He also uses a gene knockout technique called CRISPR. Vakoc is inhibiting parts of proteins in animal models of this disease and examining how the sarcoma responds.

“This is a way to provide a road map for where drug discovery should be,” Vakoc said.

Once he and his lab finds these targets, they can look for existing drugs approved for other clinical applications that might work against this cancer. His first round of screens have nominated some targets, although it is too early to know if these will prove useful in treating RMS, Vakoc said.

With Brd4, Vakoc found a target in which an inhibitor already existed. Based on his research, scientists are now conducting a clinical trial to study its effects.

Keller used to see patients but now conducts research full time. Any discovery with RMS might have implications for other diseases, he said. The most commonly known inherited predisposition to cancer, called Li-Fraumeni syndrome, was originally reported as a condition of inherited RMS. This syndrome, Keller added, has mutations in the p53 genes, which is one of the most well-studied genes in cancer of any type.

“Pediatric cancers can lead to fundamental types of discoveries that are later paradigms for adults cancers,” Keller explained. Keller also recognized Stillman’s role in creating the partnership with Vakoc. “There is something very personal about [Stillman’s] desire to make a change for this disease,” Keller offered.

Indeed, after meeting with some of the families affected by RMS, the members of Vakoc’s lab have contributed more of their time to seeking a cure. Vakoc said his lab members attended a one-hour talk Keller gave that included people from the foundations. Keller discussed the unique challenges of this cancer.

“Seeing the reactions and hearing the questions families have puts a different perspective on cancer research” from what scientists who study molecules in a lab “normally encounter,” Vakoc said.

He praised his lab mates for coming in on the weekends for a few extra hours of work. They are also planning to volunteer at the Morgan Center, a group that supports preschool children with cancer.

Keller said he’s thrilled with his collaborator. He said his mentor, Nobel Prize winner Mario Capecchi had a saying: “Go with the best, no matter where they are.” That, he explained, is Vakoc.

Keller and Vakoc are using the philanthropic support to involve Novartis in a grant they have submitted to the National Institutes of Health, Keller said.

Paul Paternoster, who lost his wife Michelle to RMS last year, explained that it is “nice to drive by Cold Spring Harbor Laboratory every day and think about” how researchers are working toward a cure. “We took all the pain and negative energy” that comes from battling this disease “and turned it into something positive.”

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Joel Saltz lives in a world of numbers. The first chairman of biomedical informatics at Stony Brook recently hit a number that will help him continue to develop a department he arrived to lead last year: $3.2 million. That’s how much the National Cancer Institute pledged to support Saltz’s efforts.

“This grant is related to developing methods and tools for analyzing tissue data, in particular pathology, as it relates to genetics and genomics,” Saltz said. That means he will try to understand more about the complex patterns of interactions between cancer cells, surrounding and distant tissues. By studying these interactions, Saltz and his collaborators hope to help develop diagnostic and treatment methods.

A powerful enemy with ways of evading different kinds of treatment, cancer can present prognoses that vary from one person to another — even when the cancer is in the same area or affects the same organs or systems.

“In some cases, the relationship varies from one part of the tumor to another,” said Saltz. “If one part of the tumor has ‘x,’ they treat it like ‘x,’ but if it has some ‘y,’ the heterogeneity can be indicative of another diagnosis. What you want to do is look at the distribution of proteins or nucleic acids, and then do an image analysis.”

Saltz has programmed computers to scan tumors to get a consistent, quick and reproducible understanding of the underlying cancer or tumors. This effort will provide data that the international community of academic and commercial algorithm developers can study.

This effort to count different types of cells to get a mathematical handle on the type of disease can “reduce the variability from one pathologist to another,” Saltz said. “That is critical for any study.” He also hopes to learn new relationships among various components that may not be obvious.

By understanding the nature of the specific cancer, scientists and doctors hope to get a better handle on a specific treatment for each patient.

Saltz is “working with a number of translational researchers” who have patient populations or are working with animal models of cancer, he said.

The kind of analysis Saltz does in his biomedical informatics world may eventually lead to individualized or precision medicine. At this point, this is a longer-term hope for the effort.

Saltz described the process as taking an image analysis and adding a machine learning component. While convinced of the value of this type of computer-aided analysis, Saltz is not advocating developing a diagnostic or treatment regime by relying exclusively on the analysis of a computer.

“The sort of information a machine can give you complements what two people trained in different parts of the country” conclude, he said. “It can help reduce the level of unanticipated disagreement.”

At this point, these methods are not directly used to treat patients. They are a part of a research effort to improve the quality of the scientific studies.

Saltz credited Ken Kaushansky, the dean of the School of Medicine, with committing Stony Brook to integrate the latest research into improvements in the care and treatment of patients.

Other Stony Brook scientists shared their appreciation for Saltz’s approach. Saltz “brings in unique and urgently needed expertise in cancer informatics,” said Yusuf Hannun, the director of the Stony Brook Cancer Center. “This is a discipline engaged in collating, organizing and analyzing large data sets obtained in the course of cancer studies. Saltz brings internationally recognized expertise in this field.”

Saltz said there were numerous steps researchers needed to take before this approach has a clinical application.

To build out the expertise in biomedical informatics at Stony Brook, Saltz is applying to add a Ph.D., Master’s and certificate program. He said the program will build a bridge between pathology and computer science.

A resident of Huntington, Saltz moved to Long Island with his wife Mary, a clinical associate professor of radiology. The couple have four children, who range in age from 19 to 26.

Saltz said he was impressed with the natural beauty of Long Island. He had visited the area before when his brother, David Saltz, who is now at the Department of Theatre and Film at the University of Georgia, worked at Stony Brook from 1994 to 1996.

As for his work, Saltz said he is “delighted” with the NCI grant. “We’ve got a great team.”

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While the United States was celebrating Independence Day two years ago, a group of people were cheering the discovery of something they had spent almost half a century seeking. Physicists around the world were convinced the so-called Higgs boson particle existed, but no one had found clear-cut evidence of it.

At a well-attended press conference, scientists hailed the discovery, while recognizing the start of a new set of experiments and questions.

As a part of the ATLAS team, Marc-Andre Pleier knew what the group was set to announce. He was very excited “to see the signal confirmed by an independent measurement.” Two years later, Pleier, a physicist at Brookhaven National Laboratory and a part of a group of more than 3,000 scientists from around the world, are tackling the next set of questions.

The discovery “points to the Standard Model [of particle physics] being correct, but to know this we need to understand this new particle and its properties a lot better than we do now.”

According to the Standard Model of particle physics, the Big Bang beginning to the universe should have created equal parts matter and antimatter. If it did, the two opposite energies would have annihilated each other into light. An imbalance, however, resulted in a small fraction of matter surviving, forming the visible universe. The origin of this imbalance, however, is unknown, Pleier said.

“We know the Standard Models is incomplete,” he said, because there are observations of dark matter, dark energy and the antimatter/matter asymmetry in the universe that can’t be explained by this model. “We can test this” next chapter.

The process Pleier studies allows him to test whether the particle is doing its job as expected. In addition to analyzing data, Pleier also has “major responsibility in upgrading the detector,” said Hong Ma, a group leader in the Physics Department at BNL who recruited Pleier to join BNL in 2009.

Scientists at the Hadron Collider in Switzerland and at BNL and elsewhere are studying interactions that are incredibly rare among particles.

Pleier is searching for interactions of vector bosons, which have spin values of one and are extremely large in the world of bosons. He is looking for cases where two W bosons interact with each other.

“Only one event out of a hundred trillion events will be of interest to me,” said Pleier. Comparing those numbers to the world of biology, Pleier likened that to finding a single cell in an entire human body.

In 2012, the Hadron Collider produced 34 such interactions. The collider produces about 40 million pictures per second. To find the ones that might hold promising information, scientists like Pleier need to use a computing grid. BNL is one of only 10 tier 1 centers for ATLAS and the only one in the United States. Thus far, scientists have been able to look at these collisions from energies at 8 trillion electron volts. They hope to measure similar data at 13 trillion electron volts next year.

Ma said the increased energy of the collider will “put the Standard Model to an unprecedented level of tests,” allowing scientists to “measure the properties of Higgs boson to a higher precision.”

Growing up in Germany, Pleier said he loved playing with Legos to see how things worked. He helped fix his own toys. When he was older, he worked to repair a motor bike his uncle had.

What he’s doing now, he said, is exploring the fundamental building blocks of matter and their interactions. He likened it to examining the “construction kit” for the universe. While he’s a physicist, Pleier explained that he’s a Christian. “Some people think it has to be in conflict, but, for me, it clearly is not,” he said. “Each discovery adds to my admiration for God’s creation.”

A resident of Middle Island, Pleier lives with his wife Heather, an English teacher who is staying home for now to take care of their three children.

Pleier and Ma emphasized that the work at the collider is a collaborative effort involving scientists from institutions around the world.

Michael Kobel, a professor at TU Dresden, head of the Institute for Particle Physics and Dean of Studies in the Department of Physics who has known Pleier for about nine years, likened the process of studying the high energy particles to exploring a cave, where scientists “get more light to look deeper” into areas that were in the dark before. Researchers, he said, are just entering this cave of knowledge, with “a lot of corners yet to be explored.”

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Human mistakes occur everywhere, from a driver who runs a red light to a professional athlete who literally drops a ball, to an accountant who adds the wrong numbers. Even scientists, with their lab coats, their scientific method and their careful review process make errors.

So it was, in 2013, when scientists in Switzerland published a research paper suggesting that boron could exhibit a similar behavior to a topological insulator. If true, that could have implications for nanotechnology.

Recently, however, postdoctoral student Xiang-Feng Zhou at Stony Brook University, working with his lab director Artem Oganov, discovered that their fellow researchers had made a mistake. The Swiss scientists had “suggested metallicity for boron’s surface and this turned out to be an incorrect suggestion,” said Oganov.

Typically, topological insulators are made up of heavier elements. The Swiss scientists believed that the surface atom rearrangements in boron would enable the lighter element to exhibit the same conducting properties.

Zhou was able to test this theory by using a high-powered computer system created by Oganov and his colleagues. Called USPEX, for Universal Structure Predictor: Evolutionary Xtallogaraphy, the prediction code uses a set of principals driven by quantum mechanics.

Zhou and Oganov, who is a professor of theoretical crystallography at Stony Brook University, published their results recently in the journal Physical Review Letters, a journal of the American Physical Society.

“Topological insulators must include heavy elements and metallicity of their surfaces does not come from structural reconstructions,” Oganov said. “For boron, a similar effect was predicted (as we now know, incorrectly) due to the reconstruction of the surface.”

The Swiss scientists knew that breaking a solid causes a cleaving of many bonds, Oganov said. Atoms near the surface try to compensate for the lost bonds. Often, this results in unusual chemistry, he continued. The Swiss scientists thought this would lead to metallicity, he said.

Using their computer model, Zhou and Oganov found that boron would have a much more stable structure if it avoided a metallic state. Instead, it forms a semiconducting surface.

When Zhou, who is also an associate professor of physics at Nankai University in Tianjin, China, and Oganov sent their results for publication, the editors at Physical Review Letters did what they always do: they sent the paper to several experts in the field for review. One of the groups overseeing the analysis of the Stony Brook scientists’ results was the original team from Switzerland. Oganov wasn’t sure how they’d react.

“Usually, people are upset when their results are disproven,” Oganov said. “They checked our calculations and found that our result is correct. They gracefully admitted a mistake. Often, people would fight even knowing they are wrong.”

The Swiss scientists said they didn’t find the right surface because they didn’t have enough computing power, Oganov said. They suggested to Oganov that they finished their calculations “too soon.”

Another reviewer confirmed the result was correct, while a third one suggested the result might not even be worth publishing because it was something a scientist might be able to come up with using a pencil and paper.

“I take this as a compliment,” said Oganov. “Simple and beautiful are sometimes hard to come by. Heavy computations like the ones we have done are often the best way to find the simple reality. Reality is not always simple.”

Oganov credits Zhou, whom he met over five years ago and recruited to join his lab on one of his annual trips to China, with pursuing this work.

What Zhou found was “absolutely surprising and unexpected. I couldn’t expect the Swiss paper would be so far from the solution. I give [Zhou] credit for his inquisitiveness. It is hard and beautiful work.” Zhou said he met Oganov when he was a Ph.D. student. He found that the two of them had similar interests. “I love predicting crystal structures,” Zhou said.

Oganov was born in the Ukraine and raised and educated in Russia. He has worked in the UK, Switzerland and the United States. While science has a discipline and approach that keeps researchers from making unsupported claims, scientists still make mistakes. “Nobody,” he offered, “is insured from making mistakes.”

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Picture a child on a bike circling the neighborhood. If the bike path has hills and valleys, the child needs to pedal harder to climb the hills, and can coast down to the valleys. When the child stops pedaling and lets the bike stop on its own, it is likely to rest at the bottom of a valley, the way an apple that falls from a tree at the top of a hill will come to a stop after rolling to the bottom.

Jin Wang applies the same logic to cells and cancer. A faculty member in the Chemistry Department and an adjunct faculty member in Physics at Stony Brook University, Wang said the interaction between the contours of a landscape and the energy to move around that space affects a cell’s fate.

“We have been looking at the underlying gene regulatory networks of cancer,” Wang said. “The normal cell, a cancer state, and apoptosis (or cell death) are all represented by valleys.”

Wang has been looking at the influence on the driving force from individual genes and gene regulations, or links between genes. He is planning to consider multiple genes and gene regulations.

“The way the genes are connected influences the shape of the underlying landscape, making it more or less likely to enter a particular phase,” he said. A deeper cancer valley could make it easier to get into that state and tougher to get out.

A physicist by training, Wang doesn’t have a lab where he does experiments at a bench. He collaborates with other researchers, develops mathematical models and analyzes the results.

Wang and his post doctoral student, Chunhe Li, recently published a paper on the hills and valleys in cancer in the Journal of the Royal Society Interface.

Wang said the cancer state is already present in many people’s genes, but they don’t necessarily get there because it is shallower with a lower probability, the barrier is too high or the force pushing in that direction is not enough. A mutation or the environment can change the shape of the landscape, tilting it towards cancer.

Wang also published work he’s done on something basic to the life of a cell, called the cell cycle. Cancer corrupts the speed of the cell cycle, often causing cells to grow and divide at a rate that is faster than normal.

In the cell cycle, a cell goes through several well-documented stages before it divides in two. During the interphase, the cell has a G1 period, where it prepares to copy its genes, or DNA. In the S phase, it builds a genetic twin, and in the G2 period, it goes through a stage where it checks to make sure the process worked correctly. At the end of G2, it goes into the M stage, where it divides.

Wang, Li and collaborators in China explored the landscape as the cell moves from one period to another. “We have a three dimensional shape of the cell cycle,” he said.

What drives the cell through these stages is a combination of the depth of the valleys and the nutrition in the cell. “The underlying landscape for the cell cycle for cancer and the normal state is different,” he said. “The hills between valleys for cancer may be lower so that traveling through the different valleys is easier.”Wang and Li published their paper in the Proceedings of the National Academy of Sciences.

Li, who has worked with Wang since 2012, called the approach Wang has taken with landscape and flux “original.”

“The landscape shape can be used as a potential way to design anti-cancer strategies, by targeting multiple genes and gene regulation patterns,” Li explained. “These findings shed light on the understanding of cancer mechanisms and provide some insight on cancer treatment.”

Wang explained that his framework for understanding the combination of a driving force and a contoured environment could also have applications in other arenas, such as psychology, where people have natural steady-state valleys which require different levels of energy to change.

Wang grew up in China, where both of his parents were chemists. He has been on Long Island for a decade. He has an appreciation for something many residents take for granted. “I like to watch the clouds moving,” he said. “Because Long Island is in a special geographic location, the water keeps vaporizing and going out” to form clouds of different shapes and speeds.

Wang sees other arenas to apply his framework, including in psychology and decision making. Future questions could include, he said, “How do you make a decision from an undecided valley to a decided valley?”

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Seeing isn’t just believing — it can also lead to understanding. David Jackson of Cold Spring Harbor Laboratory has developed a way to see just what’s happening with important signals inside the cells of maize, a crop plant that is used in everything from cattle feed to corn syrup to oil, and even glue.

“We want to figure out what’s going on inside the cell: how they respond to treatment or processes,” said Jackson, a professor at Cold Spring Harbor.

Jackson and his collaborators use fluorescence to see proteins and hormones in action. They are not the first to use this technique in living cells, but they are the first to apply it to maize.

Labeling molecules can allow scientists to see where they go “during growth and development,” said Anne Sylvester, a professor in the Molecular Biology department at the University of Wyoming, who worked with Jackson to develop this technique. This allows researchers to see how a protein is regulated, what it’s doing and even suggest ideas on how to control it.

Jackson and Sylvester have made a large collection of these reporter lines and have sent them out to “hundreds of labs,” so other researchers can “use the tools we’ve generated,” Jackson added.

In his lab, Jackson is focused on how the plant establishes and maintains stem cells — which are like blank pieces of biological clay that genes and other molecules can mold into anything in a plant.

At the same time, Jackson and the six post doctoral students in his lab are working on several other projects. In collaboration with Doreen Ware’s lab at Cold Spring Harbor, Jackson has been taking huge amounts of data to explore how genes work together.

“We found connections between different genes we’ve been studying for a long time,” he said. “We didn’t suspect” that link before, but, “in hindsight, it makes perfect sense.”

In a paper published in March in Genome Research, Jackson, Ware, and Andrea Eveland, an assistant member of the Donald Danforth Plant Science Center, among others, showed that the transcription factor Ramosa1 and Knotted1, a regulator of stem cell maintenance, were teaming up to control branching. This, the authors explained in their paper, is an important factor in crop yield, affecting seed number and harvesting ability.

Jackson has “been making great strides in discovery of novel components of stem cell signaling, and translating these findings directly to crop improvement, which really is the ultimate goal of our research as plant scientists,” said Eveland, who worked as a post doctoral student in Jackson’s lab for more than five years.

In addition to analyzing data on genes, Jackson and his lab use Crispr, a tool that is the DNA equivalent of the game Jenga, which can knock out individual pieces, allowing them to see the effect on the plant.

“Many genes are redundant,” he said, so knocking one out doesn’t necessarily change anything because, like a car navigating along a detour, the plant can take an alternate genetic route to arrive at the same destination.

Jackson has won fans among his collaborators. Sarah Hake, the center director of the USDA Plant Gene Expression Center at the University of California at Berkeley, and Jackson’s post doctoral mentor, called him “a superstar.” He has “brilliant ideas” and is “well known in maize genetics and developmental biology.”

He also requires precision and accuracy among his fellow scientists.“When someone showed data at a lab meeting that was poorly done, he would politely call it rubbish,” Hake recalled. “He set a high standard that kept our lab at the top.”

At the same time, Jackson has been an “incredible teacher” and role model to scientists in training. He has contributed to Sylvester’s outreach programs in Montana to help teach genetics and cell biology at a tribal college for Native Americans.

While Jackson doesn’t do any lab bench-work anymore, he conducts field work at a Cold Spring Harbor Laboratory farm during the summer and in Puerto Vallarta in the winter.

Jackson and his wife Kiyomi Tanigawa, an interior designer, live in Brooklyn with their six year-old son, Toma.

Originally from the north of England, Jackson has been at Cold Spring Harbor for 17 years.

In his work, Jackson said he is thrilled with the advances in technology.

“There is a revolution in biology,” he said, adding that Crispr, and other tools, will “open up so many different areas we can address.”

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For Annie Heroux, it was love at first sight, at least as far as her career was concerned. During her days of studying at the Universite de Montreal, she took a course in crystallography — the study of the structure of small objects by looking at a crystallized arrangement of their atoms.

Even before the class began, she read the entire book. When she saw the professor, Francois Brisse, she said, “This is what I want to do” in graduate school. And so she did.

“I never planned for it,” she said. “It just happened.”

For her graduate work, Heroux performed crystallography work on polymers like kevlar. Eventually, her interest took her to Brookhaven National Laboratory, where she’s been for the last 13 years.

A beamline scientist, Heroux provides a supporting role to many of the users from around the world who come to BNL to see if they can make a link between the structure of something small that often happens inside a cell and its function.

“It is like knowing the shape of the tiny gears in a watch — OK, an antique watch with gears — and then desiring to know how the gears move each other to count down time, or move a muscle or have a thought,” explained BNL colleague and fellow Beamline Scientist Howard Robinson.

Recently, Heroux worked with Scott Bailey, an associate professor in the Johns Hopkins Bloomberg School of Public Health’s Department of Biochemistry and Molecular Biology. Bailey explored how bacteria were able to recognize and destroy viruses.

Heroux helped provide the first picture of the RNA and DNA of a molecular tool called Cascade, which protects the bacteria.

Cascade, an 11-protein genetic security system that can only function if each part is working correctly, uses short strands of bacterial RNA to scan its DNA to see if the genetic blueprints come from something else that might be trying to corrupt its system. If the RNA recognizes something other than its own code, it breaks down the DNA.

Heroux helped explore more conditions to get better crystals with better diffraction qualities — or ways that light bends.

In this research, which was published in August in the journal Science, Bailey and his collaborators found that the RNA scans the DNA in a way similar to how we look through text for a single word. The Cascade has a template to find its compatible counterpart.

In general, Heroux said her role is to make sure that everything works the way it should at the beamline. She “goes through the steps to figure out all the things that can go wrong during an experiment.”

After she helps with experiments, she returns to “crunch the numbers on the computer.”

While she doesn’t have her own lab or pursue her own research agenda, she does have an opportunity to try to figure out new ways to solve the structure of a molecule in a different way.

Heroux is looking forward to the opportunities presented by the NSLS II, the second generation of synchrotron that will open officially in 2015. The beam, which is 10,000 times brighter than the original, will create new opportunities and new challenges.

“The beamline will be so bright that we will modify the way we do experiments,” she said. The X-rays have the potential to destroy the crystals. The experiments will have to occur at a faster speed and may require more crystals to get a full data set.

Heroux enjoys the process of collaborating with scientists on their projects.

“Most scientists are pretty centered over what they want to do,” she said. “What I find interesting is that, by collaborating with all kinds of different groups, I get to see all kinds of different problems. It’s never the same thing.”

A resident of Shirley, which is only seven minutes from the lab, Heroux lives with her partner, Matt Cowan, a computer expert. Heroux, who is originally from Montreal, met Cowan through her work.

The couple have three children: Viviane Trudel, 21, Florence Trudel, 18 and Ethan Cowan, 10.

Heroux enjoys walking through parks with a mycology club, which searches for and identifies mushrooms. She calls cooking her “big relaxation,” and has tried her hand at Indian and Mexican food. She has also made her own sushi.

As for her work, she still is excited about seeing the structure of objects.“You collect data, which are spots on your detector and, if you’re lucky, a couple of hours later, you see the structure popping up,” she said. “That is always exciting, no matter what the structure is.”

 

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Ominous forecasts start a cascade of reactions, from a race through the supermarket for canned goods and water to trips to the hardware store for batteries and flashlights to a rush to the gas station to fill up before the possibility of an interruption in the supply line.

Stephanie Hamilton is determined to turn predictions of an approaching storm into a new kind of action plan for utilities.

A Smarter Grid R&D Manager at Brookhaven National Laboratory, Hamilton recently received a $336,000 grant from the New York State Energy and Research Development Authority to work with two utilities in upstate New York, Orange and Rockland Utilities and Central Hudson Gas and Electric. She would like to help these utilities gain a better understanding of how to interpret and use weather data to develop a plan for approaching storms.

The elements of new information in the BNL study will include streaming radar that offers forecasts in a range of 1.5 kilometers.

“What this will tell them is where we think the storm is going to be, the volume of the precipitation and how long that might continue,” Hamilton said.

That kind of specific knowledge of a storm will aid companies in understanding where to put reserves in place by reaching out to other companies through a mutual aid assistance program in states that might not be as affected by a storm.

When Hurricane Sandy hit, for example, Orange and Rockland Utilities had over 4,000 workers come to help restore power. Wisconsin Gas and Electric sent crews to Long Island to aid in the storm recovery.

Hamilton and her colleagues are working on building a toolkit that will help utility personnel use weather information they currently don’t have.

“Our expectation is that by having the information and new tools,” these companies will be able to understand “how severe weather will impact their systems.”

— Stephanie Hamilton

Hamilton said she herself isn’t the weather expert: she is relying on the meteorological expertise of BNL scientists Michael Jensen and Scott Giangrande. She is hoping to bring together the skills at understanding severe atmospheric conditions with an awareness of the vulnerable points on an electric grid.

Hamilton’s former supervisor, Gerald Stokes, who is now a visiting professor in the Department of Technology and Society at Stony Brook University, praised her work and her approach. Hamilton is “well regarded in the smart grid and utility community and is seen as one of the pioneers in that area,” he said.

The BNL study is one of seven such efforts NYSERDA is sponsoring with a total of $3.3 million to help utilities prepare for and react to severe weather events.

“As we continue to witness the impacts of extreme weather, it is more important than ever to invest in making our energy infrastructure stronger and smarter,” Gov. Andrew Cuomo said in a statement.

Hamilton hopes this is among the first steps in what could be a lengthy and productive local analysis of the vulnerabilities of the system to various disruptions. Some utility poles might be in areas where the ground becomes saturated with only a few inches of rain, depending on the local conditions and the ability of the vegetation in the area to soak up any accumulations.

When this project ends, the BNL team will try to demonstrate the tool at the utility with their existing procedures to validate the model and see how it can be used, she said.

Down the road, the utilities could integrate this kind of analysis with a pole-by-pole understanding of vulnerabilities to specific weather conditions.

The utilities have a financial incentive to bring systems damaged by a storm back online. Hamilton said a one hour reduction in storm response could save Orange and Rockland Utilities about $100,000 to $200,000.

A resident of Manorville, Hamilton lives with her partner John York, a retired Army lieutenant colonel and an IT expert working with TIAA-CREF in New Jersey as a business analyst for computing systems. Hamilton has enjoyed her three and a half years at BNL after growing up in south Georgia and spending much of her career in western states, including California, Washington and Wyoming.

As for her work, she feels at home at BNL.

“This is really a culmination of all the things I’ve ever wanted to do,” she said. She relishes the opportunity to “move the industry ahead. Making [utilities] more reliable and resilient is the key to our economy.”

 

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In the 1970s, when he was in graduate school at New York University, Thomas Gingeras said his late mother, Barbara Lammons, described him as a vet for flies. While earning his Ph.D., Gingeras brought home bottles of one of the more common scientific test subject, the fruit fly, and stored them in a bathroom.

Almost four decades later, Gingeras, a professor at Cold Spring Harbor Laboratory, still works with flies, although he doesn’t need to bring any of them to his home on the campus at the laboratory. Instead, he is one of the leaders in a group called Encode, for the encyclopedia of DNA elements.

The Encode project includes scientists from around the world and provides a detailed catalog of genetic elements.

The latest version, called modEncode, for the Model Organism Encyclopedia of DNA Elements, compares genetic elements of humans to those of flies and the roundworm, two of the more actively studied by science.

Using billions of pieces of information including DNA base pairs and messenger RNA, scientists were able to explore the overlap in genetic machinery among members of species with considerably different lives.

“What we see,” Gingeras said, “are patches of things where the sequences that are known to carry out specific functions relate to one another.” These results were recently published in the journal Nature.

He likened the study to an examination of paintings. Looked at from a distance, the way a fly, worm and human might be seen, the end product appears different. “When you look at small areas, you can see” similarities among the paintings.

By finding overlap, scientists can hone in on ways to repair damage and provide additional genetic targets to cure human disease. “This points us in the direction of setting these at the top of the priority list,” said Gingeras. One of the primary paths pharmaceutical companies pursue is that “they look to find a disease state that is closely mimicking what is happening in humans. They look to see if the cause is similar, in their genes and regulatory regions.”

In his lab, Gingeras has five people who do benchwork, producing genetic data. Another five dedicate their time to making sense of that information, plugging bits of data into computers and looking for meaningful overlaps. Gingeras divides his time between analyzing and interpreting the data, writing for grant money and summarizing results in research papers.

Gingeras said the Encode group has been through some battles in the scientific community, especially when they first proposed the idea that the genes that don’t code for a specific element still might have a function for the organism and for the cell.

“The predominant idea when the human genome sequence was deciphered is that only a small fraction of the genome was functional,” about 2 percent, Roderic Guigo Serra, coordinator of the Bioinformatics and Genomics Program at the Center for Genomic Regulation in Barcelona explained in an email. “Gingeras “demonstrated that the fraction of the genome that is transcribed is much larger,” closer to 60 percent or more. Initially, Gingeras’s results were viewed with skepticism; they are now “widely accepted.”

Gingeras admitted that the early criticism bothered him.

“I took it very personally,” he said. “Not too long into this process, it dawned on me that it doesn’t make any difference what anybody thinks. If it’s right, [other scientists] will see it for themselves.”

Serra, who started collaborating with Gingeras more than a decade ago, said his colleague has “amazing energy,” and can call him to discuss their work at almost any hour of the day. This, he said, has been challenging but also motivating for Serra. Gingeras “has the insight to anticipate the questions that will become important before others,” he said.

Gingeras and his wife Hillary Sussman, who is the executive editor of the journal Genome Research at CSHL, have a 12-year-old daughter, Noa Sussman and a 5-year-old, Arie Anna Gingeras.

As for his work, Gingeras said the next steps in the analysis of genomes could include other organisms.

“The intention has been, all along, to provide a blueprint of what you could do on any organism to understand better what the component parts of the organism are,” he said. “This effort is meant to be a model case of what you could do for all organisms. The next step is to do the same thing for other organisms or study systems.”