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Maureen O’Leary on an expedition in Mali. Photo by Eric Roberts

By Daniel Dunaief

At their greatest depths, oceans hold onto their secrets. With layers of light-blocking water between the surface and the bottom, they hide the kind of clues that might reveal more about who, or what, lived or traveled through them.

What if a sea dried up millions of years ago? And, what if that sea left behind pieces of information — some of them small and subtle and others larger and easier to spot? That’s what happened in a part of Africa that long ago gave up any signs of flowing water. The Sahara desert was, millions of years ago, home to an inland sea called the trans-Saharan seaway.

Maureen O’Leary, a professor in the Department of Anatomical Sciences in the School of Medicine at Stony Brook University, has been to Mali, a country in the northwest of Africa, three times on expeditions, most recently in 2008. There, she collected fossils that are members of extinct groups that are part of larger evolutionary units with living members today.

O’Leary has explored and cataloged a number of remnants from the region, including a turtle and crocodile skull. She and her collaborators have also discovered sting ray fossils. Originally considered likely residents after an asteroid hit Earth that caused a massive extinction, these fossils now suggest that these sting rays lived in the area earlier than previously believed.

“This suggests that the sting rays did survive” the asteroid impact, said O’Leary. “Often extinction events are described in very broad terms but specific studies like this help us” hone in on the kind of species that survived.

She also found intriguing deposits in fossilized feces. Invertebrates burrowed through these fossilized remains, leaving a cast of the shapes of their bodies. The group that left traces of their activities in fossilized feces includes Pholadidae, which has living members. “A careful inspection of a whole fauna of fossils allows you to find invertebrates you had no record of,” said O’Leary.

Leif Tapanila, the director of the Idaho Museum of Natural History and an associate professor of geosciences at Idaho State University, joined O’Leary on an expedition to Mali in 1999, where he was the invertebrate expert. Tapanila said the feces of sharks, crocodiles and turtles have bone fragments that tend to preserve well. Some of these fossilized feces can be four- to five-feet-thick deposits. A prehistoric diver from 30 million years ago would have found that the bottom of the seaway, which was probably 50 to 70 meters at its deepest points, was covered in these hard feces, Tapanila said.

Tapanila described O’Leary as an effective collaborator who ensured scientists formed effective partnerships. “She brings people together,” Tapanila said. “One of her biggest strengths is that she finds pieces of the puzzle that are needed for a particular scientific question. She sets up the infrastructure to make a research project work.”

In one of the blocks of limestone recovered in 1999, O’Leary found a crocodile skull with well-preserved ear bones. That level of detail is unusual in a fossil because of the relatively small and fine nature of those bones. Robert Hill, who was a doctoral student in O’Leary’s lab and is now a professor at Hofstra University, noticed that the ear bones had bite marks on them. A closer examination suggested that the marks were made by a shark, either during a prehistoric battle or after the crocodile had died.

O’Leary is currently working with Eric Roberts, the head of Geoscience at James Cook University in Australia, to write a review paper on Mali that would contain some reconstructions of the region and the species. The paper would emphasize a big picture story using the specialized details she and others collected. This will not only help people see the world as it was but also may help them see the Earth as a changing place, where rising sea levels could cause another transition in a dry and arid region.

While O’Leary would like to return to Mali, she and numerous other scientists have kept their distance amid the political instability in the area. In 2008, Canadian diplomat Robert Fowler was taken hostage for 60 days. “There were some diplomats there who seemed unflappable and serious” who suggested that O’Leary and her colleagues return home during their expedition. “The American Embassy was instrumental in leaning on me to leave.” O’Leary said the politics of these areas, despite the rich story they may have to tell about the past, “can play into whether science can even be done.”

In addition to her research in Mali, O’Leary raised the money and created an online system called MorphoBank, which enables scientists studying anatomy all over the world to collect their information in one place. MorphoBank encourages those interested in anatomy of any kind to find data in one place. Tapanila credits O’Leary for creating a valuable resource. For the time, MorphoBank was “totally new. It takes a lot of effort and vision to pull that off,” he said.

O’Leary is married to Michael Novacek, an author and senior vice president and curator in the Division of Paleontology at the American Museum of Natural History. He is one of the team leaders of the joint American Museum of Natural History/Mongolian Academy of Sciences ongoing expeditions to the Gobi Desert. The duo, who collaborated on an expedition in Morocco, have co-authored papers on the philosophy of science, placental mammal evolution and a team-based study of mammal evolution that was published in the journal Science.

O’Leary watches the political scene in and around Mali from afar.“I do keep an eye on it and would love to return,” she said.

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Wei Zhu with a photo of her mother, Shenzhen Du. Photo by Joyce Ruan

By Daniel Dunaief

Wei Zhu’s long personal and professional journey began in China. Devoted to her mother, Shenzhen Du, Zhu watched her hero fight through a long illness with chronic kidney disease. Shortly before she died, her mother woke from a coma and suggested that her daughter become a doctor, like the people who were helping her in the hospital.

Driven to fulfill her mother’s request, Zhu attended college where, despite aspirations to become a writer like Charles Dickens or Charlotte Bronte, she studied math. She found the subject challenging but stuck with it. “Math was absolutely hard work,” she recalled. “We had to devote longer time to our study than many other majors. It all paid off in my case.”

Indeed, after she completed a one-year graduate program in math, she and her husband, Yeming Ma, came to the United States, where she used her experience in math to explore ways to understand how statistics can provide a perspective on everything from drug dosage to global warming to the causes of cancer.

“You can use math to improve people’s health,” said Zhu, who is now the deputy chair and professor in the Department of Applied Mathematics & Statistics at Stony Brook University.

Wei Zhu with her daughter, Merry Ma. Photo by Merry Ma
Wei Zhu with her daughter, Merry Ma. Photo by Merry Ma

At the beginning of the year, Yusuf Hannun, the director of the Stony Brook Cancer Center, emailed Zhu to ask her to pitch in to help understand a major question about cancer. In the prestigious journal Science, several researchers had concluded that the “bad luck” hypothesis suggested cancer was something that was written in a person’s genes. This scientific conclusion was akin to suggesting that a character’s fate in a play may have been written in the stars.

Hannun, Song Wu, an assistant professor in her department, Scott Powers, a professor in the Department of Pathology and Zhu came to a different conclusion, which they published in the equally prestigious magazine Nature.

Putting the data and the theory together, the group suggested that lifestyle choices and environmental exposure were also instrumental in this disease. The argument is the equivalent of nature versus nurture for a deadly disease.

“We were able to quantify what we observed,” Zhu said. For most cancers, the group concluded, the majority of the risk was due to lifestyle and environmental factors other than pure intrinsic genetic mutations. The disease debate, scientists recognize, doesn’t end there.

“The entire cancer research community still has a long way to go in order to perfectly understand the causes, prevention and treatments for each cancer, for each individual,” Zhu explained.

Hannun suggested that the direction cancer research is going requires advanced expertise in several areas of applied mathematics, physics and related disciplines. These are now needed for working with large data sets, for modeling pathways and events and for generating new hypotheses and organizing principles, Hannun wrote in a recent email. Hannun described Zhu as “terrific, highly dedicated and very collaborative” and suggested that the work has been “rewarding.”

Zhu is hoping that the recent Nature publication will trigger additional funding to support more research with this team of Stony Brook University scientists.

Wu, who was the first author on the Nature article, described Zhu as “well respected in the scientific community. She has done a lot of work on the analyses of brain image and proteomics data,” he wrote in an email.

Throughout her career, Zhu has sought to use statistics, bioinfomatics and other modern tools to enhance a scientific understanding of complex questions. She recently worked with Ellen Li, a professor of medicine and chief of the Division of Gastroenterology and Hepatology at Stony Brook University School of Medicine, who wanted to understand the development of digestive diseases such as inflammatory bowel disease and colon cancer. Putting the numbers together could provide the kind of information that offers an understanding of how lifestyle and food choices contribute to some diseases over time, Zhu said.

“We have published several papers together over the years,” Zhu said. “We are still in the data collecting stage for the diet analysis.” In her career, which spans 24 years, Zhu has worked on a wide range of topics. She has helped analyze data on the regions of the brain that are active in addiction and helped refine and enhance global climate models. In her early work, she also help pharmaceutical companies come up with optimal drug dosage. Numbers have been a part of Zhu’s life wherever she goes. “You do see numbers in the air,” she said. “When it’s getting hot,” she asks, “what does it have to do with my climate model? Does it fit the data?”

In more recent years, Zhu has struggled with the tension between contributing to larger projects and budgetary constraints. She worries that the “funding situation has changed the dynamics of the job market for the young generation of statisticians,” she said. “Now the majority of my doctoral students hope to focus their research on financial models, instead of biological models.”

Zhu and her husband Ma, who is a financial manager for GE, live in Setauket. Their son Victor, 24, recently earned his graduate degree in finance, while their daughter Merry, 11, attends Mount Elementary School. Zhu appreciates living on Long Island, where she can be close to the ocean.

As she looks back on the developments in her life that brought her to this point in her career, Zhu recognizes that the decision to learn more about math and statistics provided her with the kind of background that allowed her to fulfill her mother’s wish. “I can always honestly tell young students that it is a good idea to choose mathematics or statistics as their undergraduate majors,” she said. It will pave the way for them to have “a solid foundation for a variety of future graduate studies.”

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A drone carrying medicine and lab samples lands in a village in Madagascar. Photo courtesy of SBU

By Daniel Dunaief

Stony Brook University is taking to the skies to help people on the ground in Madagascar. Through its Global Health Institute, SBU plans to bring drones to the island nation off the southwest coast of Africa that will carry medical samples from hard-to-reach villages to its state-of-the-art research facility, Centre ValBio.

Late last month, Peter Small, the founding director at GHI, brought a drone to Madagascar, where it flew from the research station to a nearby village. The drones can fly like an airplane over 40 miles of terrain, while they take off and land like a helicopter, enabling a smooth ride to protect the samples inside the cargo area.

“Our challenge is to align the most pressing challenges that are amenable to supply chain and specimen transport and intervention,” Small said. Madagascar is dealing with “high rates of tuberculosis” among other health challenges, he said, adding that a university like Stony Brook can take complicated problems and find solutions in the real world.

The drones can provide two important functions for Madagascar: monitoring the outbreak of any unknown and potentially dangerous disease and offering health care for people who live in areas that are inaccessible by road, Small said.

A view of Madagascar from the SBU drone. Photo courtesy of SBU
A view of Madagascar from the SBU drone. Photo courtesy of SBU

“Diseases like Ebola and Zika frequently pop up in remote areas,” said Small, a medical doctor who worked at the Bill & Melinda Gates Foundation prior to joining Stony Brook University in 2015. Having sites where drones can land and collect specimens will allow village health workers to send off specimens for analysis, providing greater clarity on the incidence of specific diseases throughout the country.

Additionally, people in remote areas can send samples back to a lab to test for medical conditions, such as tuberculosis. After medical technicians run tests, the drones can return not only with drugs that can treat the condition but also with instructions on how to treat patients.

The drones can carry a special box to record whether a pill bottle is opened. The box also can carry a sound recorder that can recognize and count coughs, Small said. When the drone returns with another supply of medication, the previous medicine can make the return trip to the lab, where doctors can determine whether the cough is getting better and can see how much medicine the patient took.

Medicine is delivered to villages in Madagascar by way of drones. Photo courtesy of SBU
Medicine is delivered to villages in Madagascar by way of drones. Photo courtesy of SBU

Ideally, the drones will not require any specialized knowledge to fly. Once people in rural villages have a signal, they can request a drone, which can transport samples to a lab or bring medicine back to the village.

“We want to put these drones in the hands of the village health workers and the local health system,” said Small. He said those working with this project hoped people in the village would welcome this medical service but were unsure how it would be received. “We had no idea how people would respond to these” drones, Small said. The initial run, however, was successful. GHI plans to bring two more drones to Madagascar in the next few months.

A company in Michigan called Vayu manufactures the drones, which weigh 35 pounds, are about the size of a picnic table and can carry up to a 5-pound payload, said Daniel Pepper, the company’s chief executive officer. Using an electric, rechargeable battery, the drones can travel up to 40 miles. In the near future, Pepper hopes to increase that distance to as many as 65 miles.

Vayu has manufactured dozens of these drones. The recent Madagascar test was the first time they had used the unit in an international setting. Pepper is “speaking to partners and potential customers in over a dozen countries,” including the United States, where drones might offer a connection between medical centers in urban areas and harder-to-reach rural communities.

Pepper said the drone was the only one on the market that’s electric powered and can carry this payload over this range. “It takes off automatically and lands vertically,” he said and described the landing as “soft.”

According to Small, Madagascar could benefit from these drones, particularly in diagnosing the myriad health challenges of the area. “Madagascar is a remarkable area to start addressing some of these problems and bringing innovation,” he said.

In some villages, as many as 90 percent of people have intestinal parasites, which contributes to malnutrition and stunts growth, Small said. Small and Patricia Wright, the founder and executive director of Centre ValBio who has been working in the area for 30 years, are hoping to broaden and deepen the connection between Stony Brook and Madagascar.

The dental school has coordinated dental missions to treat hundreds of patients a day. Small said the dean of the dental school, Mary Truhlar, recently visited Madagascar to go beyond medical missions to “engage in improving the quality and training, care and health system issues.”

Small is excited with the way computational science and high-end mathematics are coming in to describe the complexities of health problems to the government of Madagascar. This will assist the government in generating medical priorities. Small has set some large goals for his role: “If life is not palpably better in five, 10 or 15 years” in Madagascar, “I will have failed at my job.”

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Dima Kozakov. Photo courtesy of Stony Brook University

A high five becomes a natural celebration after a home run because the hitter and the celebratory teammate are standing on their feet and are looking directly at each other. What if gravity didn’t keep our feet on the ground and our heads in the air? We might slap a hand into a foot or a foot into an elbow, sharing a nonverbal exchange with a different meaning.

Proteins inside our bodies don’t have the same gravitational and physical limits. They can and do come together in a soup of cytoplasm, blood, plasma and other mediums. Some of the time, those exchanges, like the high fives, communicate a message in the ordinary course of life. In other circumstances, however, those protein-protein interactions can lead to diseases like cancer.

Researchers around the world have studied these interactions using a variety of tools, trying to combat signals that contribute to damaging and life-threatening conditions.

Dima Kozakov, assistant professor in the Department of Applied Mathematics and Statistics and faculty member of the Laufer Center for Physical and Quantitative Biology at Stony Brook University, has spent several years creating a general way to model the mechanical details of how two proteins interact. This tool could become useful for researchers who are studying problematic interactions.

Leading an international team of scientists, Kozakov, who is also a faculty member at the Institute for Advanced Computational Science at SBU, created a new algorithm to model protein interactions. This algorithm accelerated how to model particular protein-protein interactions to identify harmful couplings. Kozakov and his colleagues recently published their findings in the prestigious journal, Proceedings of the National Academy of Sciences.

Applications of this technology include helping to design therapeutic proteins and speeding up vaccine design. If, for example, the interaction of a pair of proteins contributes to disease, scientists may want to design some other protein that is safe for the patient that will interact with one of the proteins. This additional coupling can avoid the more harmful protein connection.

Scientists also sometimes know that two proteins interact, but they don’t know how. Proteins often have large surfaces with many potential connections. Researchers might need to know “how two bodies come together,” Kozakov said. Proteins are flexible three-dimensional objects that consist of molecules. In modeling the interactions, Kozakov can find the three-dimensional way these proteins come together.

Computational modeling is less expensive than running experiments. At this point, the computer system needs as its starting point the three-dimensional structure of the proteins. That, Kozakov said, is much easier than determining the structure of a protein complex.

The next step is to work on methods where scientists don’t need the structure but only the chemical formula, which they can find through the amino acid sequence. Kozakov and his collaborators will use the information on the structure of similar proteins to build the models. “We’re developing a methodology that will work with the models,” Kozakov said. He described his approach as “physics based,” in which he solves a statistical mechanistic problem by using an energy function that can account for different environments.

“In principal, we can modify our energy function to account for different environments,” like changes in pH, temperature or other variables that might affect how two proteins come together. Given the way Kozakov and his colleagues designed the model, it can account for all possible configurations of two almost rigid proteins coming together.

Kozakov is also in discussions with Brookhaven National Laboratory to explore the results of small-angle X-ray scattering. The benefit of this approach is that he doesn’t need proteins in a crystalline structure, which is a requirement of crystallography. While small-angle X-ray scattering provides less information than crystallography, Kozakov said he and his colleagues can develop it in combination with other techniques where it would be equivalent.

Kozakov has been developing models since 2007 or 2008 to understand these interactions. The project in his recent paper took three years to finish. The program takes 10 to 15 minutes to run on a personal computer. Before, this kind of effort required a supercomputer.

Kozakov believes there could be other applications of this technology, where scientists could model candidate protein drugs in real time to see how the drug interacts with the protein of interest. The first version of the program came out about a year and a half ago and it took the intervening time to perfect it, he said.

Born in Eastern Europe in a region that used to be part of the Soviet Union but is now on the western border of the Ukraine, Kozakov lives in Stony Brook with his wife Olga Kozakova. The couple has a six-year old son, Platon. Kozakov’s grandparents were scientists: his grandfather, Mikhail, was a university professor and his grandmother, Nina, worked at the university. He grew up surrounded by books on physics. He “had fun, digging into antiquities books” and thought the science presented an “inspiring environment.”

As for his work, Kozakov has a big picture view of his efforts. “I want to make something useful to the community and to the world,” he said. “I want to do what I can to help.”

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Gaofeng Fan
Gaofeng Fan at Cold Spring Harbor Laboratory. Photo by Siwei Zhang

The terror in the opening of the horror movie “When a Stranger Calls” comes when the police tell an anxious babysitter that threatening calls are “coming from inside the house.”

With the killer disease cancer, researchers spend considerable energy and time focusing on signals that might be coming from outside the cell. Many of those signals bind to a receptor in the membrane that corrupt a cell’s normal pathways, leading the cell to uncontrolled growth, the production of tumors or other unhealthy consequences.

Working in the laboratory of Nicholas Tonks, a professor at Cold Spring Harbor Laboratory, postdoctoral researcher Gaofeng Fan has spent over four and a half years studying a particular signal that comes from inside the cell. I

n a recent study published in Genes & Development, Fan demonstrated that a protein called FER, which adds a phosphate group to the inside part of a receptor called MET, plays a role in the ability of ovarian cancer to spread or metastasize. Already the target of drug development, MET is overexpressed in 60 percent of ovarian tumors. Thus far, developing drugs that block MET alone has not been particularly effective. Indeed, a humanized antibody that prevents human growth factor from binding to this receptor has shown “weak anti-tumor effect” in clinical trials, Fan suggested. In his research in cells, cultures and animal models, Fan demonstrated that ovarian cancer doesn’t spread and may have a different prognosis without FER.

“We found that the ligand [the human growth factor] is not necessary for the activation of the MET,” Fan said. “In the presence of FER, without the ligand, MET can be activated.” Understanding the role of FER in ovarian cancer may offer some clues about why only preventing signals from the outside aren’t enough to protect the cell. While Fan worked with ovarian cancer, he explained other scientists have shown that FER activation has been reported in lung, hepatic, prostate, breast and ovarian cancer. FER plays a part in cell motility and invasion, drug resistance and programmed cell death.

Fan’s work with FER started with a genetic experiment. Taking FER out of a cell, through a process called a loss-of-function assay, Fan found that the cell motility, or its ability to move, decreases. Once he took out FER, he also looked closely at MET activation. If the receptor required only human growth factor, which he included in his experiment, the removal of FER shouldn’t have any effect on its activity. “We found the opposite result,” Fan said.

Gaofeng Fan with his son Ruihan at Tall Ships America in Greenport in 2015. Photo by Xan Xu
Gaofeng Fan with his son Ruihan at Tall Ships America in Greenport in 2015. Photo by Xan Xu

A set of experiments with mice provided stronger evidence to support his belief that FER played a role in the spread of ovarian cancer. One of the mice had normal FER expression, while the other was missing the FER protein. When he compared the ability of cancer to metastasize, he found that cancer spread in a more limited way in the mice without the protein. “This confirmed the in vitro data and all the cell-based assays,” he said.

After six and a half years as a postdoctoral researcher, Fan is now looking for opportunities to teach and, perhaps, start his own lab in his native China. Fan hopes to continue to work on this system and would like to be a part of the discovery process that might find a small molecule inhibitor for FER. Once he and others find a FER inhibitor, they might be able to use it in combination with other drugs, including small molecules that inhibit human growth factor’s effect on the MET receptor.

Fewer than one in four women with Stage 3 ovarian cancer, which is typically the stage at which doctors find the disease, survive for five years.

Fan said he feels driven to help find a way to slow down the progression of this disease. “There’s an urgency to find a good, effective treatment.” To be sure, Fan cautioned that these studies, while encouraging and an important step in learning about ovarian cancer metastasis, require considerable work to become a part of any new treatment.

In his work, Fan was grateful for the support of Peter A. Greer, a principal investigator at the Cancer Research Institute at Queen’s University at Kingston in Ontario, Canada. Greer “is the leading scientist in research of FER proteins and he opened up all his toolbooks to me,” Fan said.

In an email, Greer described Fan as a “very gifted scientist with an outstanding training experience.” He hopes to “continue our collaboration in the area of ovarian cancer after [Fan] establishes his independent research program” in China. Greer, who spoke with Fan regularly through the process, said he is hopeful that the publication of the study in Genes & Development, in addition to other studies he and other labs have published, will “encourage drug development aimed at FER inhibitors suitable for clinical use.”

Fan also appreciated the guidance and flexibility of his CSHL mentor Nicholas Tonks, famous for his work on tyrosine phosphatase in which he studies the effect of removing phosphate groups. Fan’s research, however, involved understanding adding a phosphate group, through a kinase. “I got humongous support” from Tonks. “Without his help, I couldn’t come this far.”

A resident of Port Jefferson, Fan lives with his wife Yan Xu, who is earning her Ph.D. in materials science at Stony Brook. The couple has a six-year old son, Ruihan, who has enjoyed the Summer Sunday opportunities at Brookhaven National Laboratory, where Ruihan spent hours viewing and constructing the structure of DNA. As for his work, Fan sees opportunities to help people battling this disease.“If we can collect more evidence from this story, we can propose” a way to boost the outcome of treatment, he said.

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Erik Muller. Photo by Yizhi Meng

By Daniel Dunaief

Diamonds may not only be a girl’s best friend, they may also be important for doctors, particularly those using radiation to treat cancer patients.

Erik Muller, a principal investigator and adjunct professor in the Department of Materials Science and Chemical Engineering at Stony Brook University, recently demonstrated that a particular type of synthetic diamond can measure the flux, position and timing of radiation beams used in cancer therapies. His research seeks to adapt diamond detectors for use with an emerging type of therapy using high-energy protons and carbon ions. “There currently does not exist a technology which can precisely measure the flux, position and timing of these proton and carbon ion beams used in radiotherapy,” Muller explained.

The diamonds Muller and his team use are more pure than any natural diamond. They contain fewer than five parts per billion of nitrogen and less boron or other impurities. They are clear with no color. Nitrogen gives diamonds a yellow or brown color and acts as a charge trap, making natural diamond unsuitable for radiation detectors.

As an SBU postdoctoral researcher, Muller joined an effort at Brookhaven National Laboratory to investigate the use of diamond as an electron source. During that study, researchers found that diamond was a valuable X-ray detector. The success of that work led to the Department of Energy funding work to develop sensors for radiotherapy.

Diamonds can provide information that enable scientists to measure in real time the development of the beam.

Once diamond growers send the product to his lab, Muller and his team screen for a defect that can lead to unwanted hot spots in the detector response to X-rays. When Muller’s lab receives the diamonds, they look like small square pieces of glass. These diamonds are bread sliced into two to three pieces that are about half the thickness of a human hair.

Partners at the Center for Functional Nanomaterials at BNL prepare, characterize, etch and pattern the diamonds in the cleanroom. The Instrumentation Division at BNL provided custom electronics, circuit design, wire bonding and assembly. “The development of the detectors, particularly the pixellated diamond X-ray detector, would not be possible without the talent and expertise” in the Instrumentation Division, Muller explained.

Muller also lauded the contribution of the Stony Brook University students who worked on the diamond effort, including Mengjia Gaowei, Tianyi Zhou, Mengnan Zou and Wenxiang Ding. In preparing a proposal for the Department of Energy to improve beam diagnostics for particle therapy, Muller met Samuel Ryu, chair of the Department of Radiation Oncology and deputy director for clinical affairs at Stony Brook University’s Cancer Center. Ryu “expressed a strong interest in using these detectors for X-ray beam therapy and we have been pursuing that as well,” Muller said.

Ryu said the existing conventional detector, which measures radiation dosage, is “limited in some sense.” He likened the radiation detector to a thermometer. If a thermometer indicates that it’s 90 degrees, it may be 91 degrees, but the thermometer may not read the temperature with enough precision to indicate the exact temperature. Similarly, the diamond detector “will improve” the precision of the radiation dose measurement. The gap in the detection of the radiation dose has been like that for more than 100 years, Ryu said.

Ryu said the addition of the diamond to the detector should be commercialized and that he and Muller are “really trying to find out how we can use these detectors in the clinic.” Ryu said he doesn’t know the time frame for when this might become available in a radiation delivery system, but he would “like to see it as soon as possible.” Ryu and his staff meet regularly with Muller and his team to analyze the data and discuss how to proceed. He described Muller as “very open-minded” and indicated that it is a “very good collaboration.”

One of the challenges in taking this diamond discovery to the next step is to ensure that the software is robust and that it has enough redundancies to turn the beam off amid any contradictory readings. Before diamonds can become a part of these carbon or ion beam treatments, researchers need to demonstrate that the radiation itself won’t damage the diamond. While Muller doesn’t expect this to happen, he said he has to prove its viability.

In the bigger picture, Muller said he and the members of his lab spend considerable time understanding the physics of radiation sensing devices in high-radiation environments. “Diamond is a very promising material in this field for continued development and is our current focus,” he suggested. “In general, I am interested in any technique and material where we can understand how the structure affects the device function.”

Residents of South Setauket, Muller lives with his wife Yizhi Meng, an assistant professor in the Department of Materials Science and Chemical Engineering at Stony Brook, and their daughter, who is in primary school. Meng, who is a graduate of Ward Melville High School, develops drug delivery materials for breast cancer and osteosarcoma, a type of bone cancer. The couple met when they were graduate students at Cornell University. They shared an interest in photography. Meng uses Nikon cameras, while Muller prefers Canon. “There’s a funny rivalry between us,” Meng said.

As for his work, Muller is optimistic that it will have an application in radiation delivery. He believes he can address the engineering challenges and is “planning to continue the commercialization of these devices.” Meng is excited by the progress Muller has been making. Muller is “working with some really great people,” she said. “It’s really exciting.”

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From left, postdoctoral associate Yuanheng Cai, biological research associate Xuebin Zhang and plant biochemist Chang-Jun Liu in the BNL greenhouse. Photofrom Brookhaven National Laboratory

By Daniel Dunaief

It provides structural support, allowing gravity-defying growth toward the sky. While it offers necessary strength, it also makes it more difficult to get inside to convert plant biomass into fuel.

Lignin is the major component that makes cell walls harder. Plants can tolerate the loss of lignin, but dramatically reducing it or altering its structure could severely affect its growth, which makes any effort to modify lignin challenging.

Seeking to balance between the plant’s structural needs and the desire to gain access to biofuel, Chang-Jun Liu, a plant biochemist at Brookhaven National Laboratory, added a step in the synthesis of lignin. “Most studies in this field rely on knocking down or knocking out one or two biosynthetic pathway genes,” said Liu. “We added one more reaction” that competes for the precursors of lignin formation. Liu said he and his collaborators figured that adding that last step in the production of lignin, which is a natural part of plant cell walls, would have the least effect on plant growth while it can effectively reduce lignin content or change its structure.

Liu said he redirected the metabolic precursor by using a modified enzyme he created over the course of several years. The enzyme diverts biosynthetic precursors away from making lignin. Plants typically have three types of lignin, called S, G and H lignin. In a wild-type aspen tree, the ratio of S to G is two to one. This change, however, altered that, turning the ratio to one to two. The general perception is that increasing G lignin would make the cell wall structure stronger and harder, making it harder to release simple sugars. The surprising finding, however, was that reducing S and maintaining G greatly enhanced the release of sugar with digestive enzymes from aspen cell walls.

Scientific partners including John Ralph at the University of Wisconsin and the Great Lakes Bioenergy Research Center confirmed the alteration of lignin structure. Liu tested his enzyme in his earlier work on the flowering plant Arabidopsis. When it worked, he moved on to aspen trees, which grow rapidly and can thrive in environments where typical farm crops struggle to grow. The aspen experiments proved more fruitful in part because these trees contained more S lignin, and the enzyme he developed preferentially blocked the S lignin. The aspen trees with the modified enzyme can yield up to 49 percent more ethanol during fermentation, compared to controls.

Using infrared light at the National Synchrotron Light Source, Liu and his collaborators were able to see an increase in the production of cellulose fibers, which are a primary source of sugars in the cell wall. This may contribute to the release of simple sugars. Liu will continue to explore other possibilities. Other lignin researchers applauded these results.

Liu’s “approach will definitely have a great impact on the cost reduction of cellulosic biofuels,” Dominique Loque, the director of Cell Wall Engineering at the Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, explained in an email. “With no impact on biomass yield and a reduction in recalcitrance, it will reduce the conversion costs of biomass to fermentable sugars.”

While this research, which was recently published in Nature Communications, shows potential commercial promise, Liu and his team are working to answer basic questions. He is interested in further testing his approach in grasses and different trees to determine the effects on lignin content, structure, cell wall digestibility and plant growth. The trees in this experiment were grown in a greenhouse, where scientists could control light and temperature and mimic the natural environment without natural stressors, like insects or fungus. Loque suggested that Liu’s approach can be “easily and quickly optimized to alleviate potential issues such as susceptibility to pathogens” if they exist.

Liu has planted 150 of these altered trees in the field. So far, he said, the biomass yield is not compromised with these experimental plants. “Field tests will allow evaluating the impact of engineering on predators, pathogens and other stresses,” Loque said. Liu was able to create this enzyme after developing an understanding of enzyme structures using x-rays at the NSLS. In that research, Liu was able to gain a better knowledge of how the enzymes that occur naturally worked. Once he knew the structure and method of operation of the enzymes in the lignin pathway, he could make changes that would alter the balance of the different types of lignin.

Liu lives with his wife Yang Chen, a teacher’s assistant in Rocky Point Middle School and their two children, 16-year-old Allen and 14-year-old Bryant. For the last few years, Liu and his family have added hiking, table tennis and tennis to their recreational repertoire.

Liu is encouraged by these findings and is extending and expanding his studies and collaborations. He will work with a Department of Energy sponsored Energy Frontier Research Center. He will also pursue more applied studies to explore the more efficient use of cell wall biomass to produce biomaterials or bio-based products. He is forming a collaboration with Stony Brook’s material science team and with the NSLS-II. “Plant cell wall represents the most abundant biomass on Earth,” Liu said. “Understanding its synthesis, structural property and efficient way in its utilization are critical for our future bio-based economy.”

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Joanna Kiryluk during her trip to the South Pole in 2009. Photo from Joanna Kiryluk

By Daniel Dunaief

She traveled to a place she felt might have been as unfamiliar as visiting the moon or Mars. The project that is such a large part of her life is looking for signals sent from well beyond those relative celestial neighbors.

Joanna Kiryluk, an assistant professor of physics at Stony Brook University, didn’t travel off the planet, although she visited a remote location that was considerably different, less populated and at a higher altitude than the sandy beaches of Long Island. In 2009, Kiryluk traveled to the South Pole as a part of the aptly named IceCube project, which was completed in 2010. Kiryluk and hundreds of other physicists around the world are studying the information gathered from detectors drilled deep into the ice below the surface.

Kiryluk is studying tau and electron neutrinos, which are created as products of cosmic ray interactions and carry very high energies. Scientists do not know which sources in the universe are capable of creating such high energies. Unraveling this is one of her research goals. The neutrinos produced by collapsing stars, or supernova, typically have energies that are about a million times smaller than the high-energy neutrinos discovered by IceCube.

Neutrinos have very small masses and travel at speeds close to the speed of light, Kiryluk explained. Since they interact with matter weakly, they pass through most objects without any interactions. On rare occasions, however, these neutrinos collide with a neutron or a proton, causing a characteristic reaction that provides a clue about where they are, what energy they had when they collided, and, perhaps where they originated.

For her research, Kiryluk recently received the prestigious National Science Foundation Career Award, which provides almost $900,000 to support her work over the next five years. “It’s a great honor,” said Kiryluk. “The chances of success for such proposals are small and, in this sense, it was also a pleasant surprise.” Kiryluk said the funding will enable her to employ two graduate students per year. Part of the money will also be used for educational purposes and outreach. Kiryluk has reached out to high schools including Brentwood and Riverhead High School to involve students and teachers in research. Kiryluk is also a proponent of a Women in Science and Engineering program, or WISE, that encourages the “involvement of under-represented groups” in science, including women.

Kiryluk credits her Ph.D. advisor, Barbara Badelek, a professor at the University of Warsaw in the Department of Physics and a professor at Uppsala University, for believing in her and in her ability. She suggested that such support was critical to her success and her focus. Badelek met Kiryluk in 1994 and supervised her undergraduate and Ph.D. work. Kiryluk was “immediately recognized as a remarkably good student: hard working, trying to achieve a deep understanding of problems and very enthusiastic,” Badelek explained in an email. Badelek added that she is “very pleased to see her maturity and growing scientific prestige.”

In the IceCube project, Kiryluk is a part of an experiment that involves over 300 scientists from 48 institutions from around the world. IceCube, which took seven years to build, was manufactured as a discovery experiment to find high-energy neutrinos, which originate from astrophysical sources. People who have known Kiryluk for decades suggest that she has the right temperament for such an ambitious joint effort.

Kiryluk is “quiet and calm, but works hard and never leaves things because she finds some difficulties,” explained Ewa Rondio, the deputy director for scientific matters at the National Centre for Nuclear Research in Poland, who met Kiryluk when she was an undergraduate. Kiryluk’s goal is to measure the energy spectrum of these neutrinos. “We are interested in fluxes,” she said. These fluxes and energy spectra of high-energy neutrinos will provide insights in the sources and mechanisms of the most powerful accelerators in the universe.

A cubic kilometer of ice, IceCube, which has enough water to fill one million swimming pools, is large enough to capture more of these rare neutrino events. The key to unraveling what these signals indicate is to understand their energy and direction. The detectors don’t collect information from the neutrinos directly, but, rather from the interaction with particles in the ice. The neutrino interactions in ice produce a flash of light in the South Pole ice that the scientists measure with sensors. They study the pattern, the arrival times and the amplitude of this light at the sensors. This information can help determine the neutrino energy and direction.

Kiryluk is looking for high-energy events that are “most likely coming from outside of our galaxy,” she said. These particles are distributed all over the sky. While IceCube is capable of collecting data from the highest energy particles, it hasn’t yet gathered enough of these events to provide conclusive information at this range.

Kiryluk visited the South Pole for two weeks in 2009 before IceCube was finished. She was involved in the commissioning of the newly deployed detectors for the data acquisition system. The detectors are between 1,500 and 2,600 meters deep, which helps them “suppress any background events,” such as cosmic rays that are produced in the atmosphere. The facility is 3,000 meters high and has low humidity, which means it’s “easy to get dehydrated,” Kiryluk said. She described the working and living conditions at the South Pole as “modern.”

A native of eastern Poland, Kiryluk arrived on Long Island in 2001, when she worked at Brookhaven National Laboratory. She lives in Rocky Point. Kiryluk said the physics department is “growing.” Since her hire, nine assistant professors have joined the Department of Physics and Astronomy at Stony Brook University. As for her work, Kiryluk is inspired to understand how IceCube can be used as a “probe to study astronomy,” which enables her to be a part of the process of discovering “what is out there.”

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John Parise Photo courtesy of BNL

By Daniel Dunaief

Finding a proverbial needle in a haystack isn’t as hard as it once was. In fact, finding a needle with specific qualities has also become easier. Manufacturers and drug companies are constantly searching for a specific substance, whether it’s a drug that targets one part of an invading fungus or bacteria or a molecule that binds to a particularly harmful gas.

Indeed, it is in this latter category where John Parise, a distinguished research professor with joint appointments in geosciences and chemistry at Stony Brook University, and a team from Stony Brook, Brookhaven National Laboratory, the Lawrence Berkeley National Laboratory and Pacific Northwest National Laboratory recently shared their use of a metal organic framework, called SBMOF-1, that selectively binds to xenon, a gaseous by-product of nuclear reactions. Their findings, which were published recently in the journal Nature Communications, may point to a more effective and environmentally friendly way to manage nuclear waste.

“This [substance] is 70 times more effective than the current way scientists remove this dangerous gas,” said Parise, who has a joint appointment in photon sciences at BNL. “It allows krypton to pass through, but it retains xenon.” Parise said it acts like a sponge absorbing water until all the pores are filled, which can then be wrung out by passing a gas like nitrogen over it.

Researchers at Pacific Northwest National Laboratory, including Debasis Banerjee, who helped create this molecule when he was a graduate student at SBU, are continuing to work on this material.

The route SBMOF-1 took to becoming a potential xenon filter underscores the collaborative nature of a process that blends basic science with engineering, manufacturing, theory and potential commercial application.

Banerjee won the President’s Award as a distinguished doctoral student at Stony Brook for his research, which involved creating this framework in 2012. When Banerjee designed this material, he didn’t have xenon or nuclear energy on his mind — he was focused on trying to extract carbon dioxide at room temperatures in a humid environment during industrial processes. “We tested this material on numerous gases except xenon,” Parise said.

What they did that led to the next step, however, was critical to the search scientists at Berkeley were conducting to find their proverbial needle. The Berkeley researchers were looking for a better way to remove xenon from nuclear waste. The Stony Brook scientists put their compound in a searchable database online, which met the criteria the Berkeley scientists had established in their search.

Instead of trying to create something new, however, the Berkeley scientists did the equivalent of digging through massive piles of haystacks to search for something that already existed, perhaps for a different purpose, that might be a candidate for the job. Sure enough, they found SBMOF-1.

“While experimentally we need to sift through a fair amount of ‘hay’ — the computer, once programmed correctly (and this is nontrivial) works rapidly to locate the needle,” Parise said.

Indeed, when the theory met the reality, krypton passed through in 10 to 15 minutes, while xenon remained trapped for close to an hour. A nuclear facility can blow air back through the material and recover most of the xenon, Parise explained.

“It’s a beautiful compound and is so much better than anything else,” Parise said, although he cautioned that “it’s not to say something else can’t do better.”

In making the material, Bernjee started looking at sodium and calcium and phenyl ring compounds. He set out to create something that was environmentally friendly.

Banerjee is continuing to work on nuclear energy at PNNL. He reflected positively on his experiences at Stony Brook University, where he conducted research from 2007 to 2012. “Stony Brook is a great place to work, particularly for research,” he explained in an email. “I still actively collaborate with [Parise’s] group.”

He described Parise as a “great mentor” and said many of his current collaborators share a similar background of working in Parise’s lab. Banerjee’s scientific teammates are either in different national laboratories or are at other universities.

Parise is a strong advocate of the process that led to this uniting of theory and practice. This procedure will give the United States a research and development edge, because the theory makes the experiments more effective and the more effective experimental results reinforce the theory.

Parise works together with people like Artem Oganov, a professor in the Department of Geosciences at Stony Brook. They are exploring new compounds to split water from sunlight. “Computational materials discovery is an ongoing scientific revolution,” explained Oganov in an email. “Calculations are playing an increasingly critical role in materials science.”

Oganov said Parise is “known as a very creative and most versatile synthetic chemist.” Banerjee added that Parise “has major contributions in the field of materials characterization using X-ray and neutron diffraction.”

A native of North Queensland, Australia, Parise started working at SBU in 1989. He is married to Alyse Parise, who is a business coach and psychotherapist, who has a private practice in Setauket. Residents of Poquott, the Parises enjoy the beaches and kayaking on Long Island. At the end of July, they will join friends to raft down the Salmon River in Idaho.

As for his work, Parise said he is dedicated to determining how the structure of compounds are arranged. “We’re interested in where the atoms are” in a wide range of materials, he said.

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Ute Moll in her lab at Stony Brook University. Photo by John Griffin

Some day, people may be able to breathe easier because of a cancer researcher.

No, Ute Moll doesn’t work on respiration; and, no, she doesn’t study the lungs. What Moll, research scientist Alice Nemajerova and several other collaborators did recently, however, was explain the role of an important gene, called p73, in the formation of multiciliated cells that remove pollutants like dust from the lungs.

Initially, scientists had studied a knockout mouse, which lacked the p73 gene, to see if the loss of this gene would cause mice to develop cancers, the way they did for p73’s well-studied cousin p53. Researchers were surprised that those mice without p73 didn’t get cancer, but found other problems in the development of their brains, which included abnormalities in the hippocampus.

While each of these mice had a respiratory problem, researchers originally suspected the breathing difficulties came from an immune response, said Moll, the vice chair for experimental pathology and professor of pathology at Stony Brook University.

A board-certified anatomical and clinical pathologist who does autopsies and trains residents at Stony Brook, Moll took a closer look and saw an important difference between these mice and the so-called wild type, which has an intact p73 gene.

Moll on a recent trip to Africa says hello to Sylvester the cheetah who is the animal ambassador in Zimbabwe. Photo from Moll
Moll on a recent trip to Africa says hello to Sylvester the cheetah who is the animal ambassador in Zimbabwe. Photo from Moll

“Microscopic examinations of many types clearly showed that the multiciliated cells in the airways were severely defective,” she explained. “Instead of a lawn of dense long broom-like motile cilia on their cell surface which created a strong directional fluid flow across the windpipe surface, the [knockout] cells had far fewer cilia, and the few cilia present were mostly short stumps that lost 100 percent of their clearance function.”

This finding, which was published in the journal Genes & Development, could have implications for lung diseases such as chronic obstructive pulmonary disease, or COPD, which affects more than 330 million people around the world and is the third leading cause of death.

The discovery provides “the long-awaited explanation for the diverse phenotypes of the p73 knockout mice,” wrote Elsa Flores, a professor of molecular oncology at the UT MD Anderson Cancer Center, in a commentary of the work.

In an email, Flores said Moll is a “wonderful collaborator and colleague” whose “meticulous” work is “held in high regard.”

Carol Prives, Da Costa professor in biological sciences at Columbia University, suggested this was a “very significant finding.”

Moll and her scientific team went beyond showing that the loss of the p73 gene caused the defective or missing cilia. They took stem cells from the trachea, which can grow on a culture dish into a range of other cells. With the proper nutrients and signals, these stem cells can grow back into a fully differentiated respiratory epithelium.

The organotypic culture had the same defects as the knockout mice. The scientists then used a lentivirus to insert a copy of the functioning p73 gene. The cells in the culture developed a complete set of long, motile cilia.

“It’s a complete rescue experiment,” Moll said. “This closes the circle of proof that” p73 is responsible for the development of these structures that clean the lungs.

In addition to the lungs, mammals also develop these cilia in two other areas, in the brain and in the fallopian tubes.

There could be a range of p73 deficiencies and some of these could be indicative of vulnerability or susceptibility to lung-related problems that are connected to incomplete cilia. This could be particularly valuable to know in more polluted environments, where the concentration of dust or pollutants is high.

Moll plans to “find tissue banks from COPD patients” in which she might identify candidate alleles, or genes, that have a partial loss of function that would contribute to the reduction in the cilia cells.

While Moll will continue to work on respiration and p73 in mice, she described her broader research goals as “gene-centric,” in which she studies the entire p53 family, which includes p53, p63 and p73.

Colleagues suggested that she has made important and unexpected discoveries with p53.

“She was among the first to show that in some pathological states, p53 is sequestered in the cytoplasm rather than in the nucleus,” Prives, who has known Moll for 25 years, explained in an email. “This led to her original and very unexpected discovery that p53 associates with mitochondria and plays a direct role in mitochondrial cell death. She was very courageous in that regard since the common view was that p53 works only in the nucleus.”

Moll was raised in Germany and earned her undergraduate and medical degrees in Ulm, the same town where Albert Einstein grew up. She lives in Setauket with her husband, Martin Rocek, a professor of theoretical physics at SBU. The couple has two sons, 26-year-old Thomas, who is involved in reforestation in Peru, and 29-year-old Julian, a documentary filmmaker focusing on environmental themes.

Moll is also focused on the environment.“If humankind doesn’t wake up soon, we are going to saw off the branch we’re sitting on,” she warns. One of Moll’s pet peeves is car idling. She walks up to the windows of people sitting in idling cars and asks if they could turn off the engine.

As for her work with p73, she feels as if she is “just at the beginning. This is a rich field.”

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