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Daniel Dunaief

Richard Moffitt, who joined Stony Brook University’s Biomedical Informatics and Pathology departments at the end of July, recently contributed to an extensive study of pancreatic cancer. Photo by Valerie Peterson

By Daniel Dunaief

It may take a village and then some to conquer pancreatic cancer, which is pretty close to what The Cancer Genome Atlas project assembled.

Pulling together over 200 researchers from facilities across the United States, the TCGA recently published an article in the journal Cancer Cell in which the scientists explored genetic, proteomic and clinical information from 150 pancreatic cancer patients.

Richard Moffitt, an assistant professor in the Departments of Biomedical Informatics and Pathology at Stony Brook University who joined the institution at the end of July, was the analysis coordinator for this extensive effort.

The results of this research, which worked with pancreatic ductal adenocarcinoma, the most common form of this cancer, offered a look at specific genetic changes involved in pancreatic cancer, which is the third leading cause of death from cancer.

“The study has several immediate clinical implications for patients facing the diagnosis of pancreatic cancer,” Ralph Hruban, one of the corresponding authors on the article and the director of the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins University School of Medicine, wrote in an email.

The work “provides hope for future clinical trials in that 42 percent of patients within this cohort had cancers with at least one genetic alteration that could potentially be therapeutically targetable, and 25 percent of the patients had cancers with two or more such events.”

These genetic findings suggest a potential basis for genetic change-driven therapy trials down the road, Hruban suggested. As the analysis coordinator, Moffitt “played a critical role” Hruban continued. “He brought hard work, amazing creativity and great scientific knowledge to the project.”

Moffitt joined this effort about four years ago, after the collaboration began. The assistant professor said he pulled together the various data sets and analysis results from different teams and helped turn that into a “coherent overall story.”

Moffitt was also in charge of the messenger RNA analysis. He had been at the University of North Carolina as a postdoctoral researcher in Vice Chair of Research Jen Jen Yeh’s lab for the last five years until his recent move to Stony Brook.

Benjamin Raphael, another corresponding author on the article and a professor in the Department of Computer Science at Princeton University, suggested Moffitt played a critical part in the recent work. “In any large-scale collaboration such as this one, there tend to be a smaller number of researchers who play an outsized role in the project,” Raphael explained in an email. Moffitt “played such an outsized role. Without his dedication to the project over the past few years, it is doubtful that our analysis” would have been as comprehensive.

Members of TCGA contacted Moffitt and Yeh because the tandem were working on a new approach to studying gene expression that would eventually be published in a 2015 Nature Genetics article.

Working with Yeh, Moffitt helped tease apart the genetic signature of pancreatic cancer cells from the different types of cells around it, which also includes healthy cells and a cluster of dense cells around the tumor called the stroma.

“The proportion of cancer cells in pancreatic cancer is low so if you imagine a mix of marbles of the same color on the outside but different on the inside and only having 10 in a bag of 100, figuring out what 10 [are] ‘tumor’ colors on the inside was very challenging,” Yeh explained in an email.

The TCGA study explains subtypes of cancer Moffitt didn’t know existed just a few years ago, while exploring the possible role that micro RNA and DNA methylation — the process of adding or taking away a methyl group from a genetic sequence to turn on and off genes — has in describing those subtypes.

Researchers “need projects like TCGA that are a really well-controlled way to study almost every molecule you want to study systematically for 150 cases to reveal these networks,” Moffitt said.

Moffitt has coupled his appreciation for algorithms and math with an interest in biology and engineering. His Ph.D. was done in a dry lab, which didn’t even have a sink. When he moved to UNC to conduct his postdoctoral work, he took a different approach and worked with surgical oncologists on tissue samples.

Moffitt plans to continue working with TCGA data and also to see how the subtypes can be used to predict responses to therapies. Some time in the future, researchers hope patients can get a diagnostic biopsy that will direct them to the specific therapy they receive, he said.

Moffitt grew up in Florida and earned his bachelor’s and doctoral degrees at Georgia Tech before completing his postdoctoral research at UNC. He has been gradually drifting north. Moffitt and his wife Andrea, who just started her postdoctoral work with Michael Wigler and Dan Levy at Cold Spring Harbor Laboratory, live in Stony Brook.

A competitive water skier during his youth in Florida, Richard Moffitt, dons two skis when he’s out with friends on Lake Oconee, Georgia in 2013. Photo by Andrea Moffitt

The water on Long Island is colder than it is in Florida, where Moffitt spent considerable time on a show skiing team. This was his version of a varsity sport, where he spent about six hours a day on Saturday and Sunday during the spring and about three hours a night before tournaments performing moving pyramids, among other tricks. When he was in high school, Moffitt wrote a computer program that automates the show skiing scoring process.

Moffitt processes the world through probabilities, which figured into the way he chose stocks in high school as a part of a stock picking competition and the way he approached his picks for March Madness. His basketball bracket won a competition for bragging rights among about a dozen entrants in 2016 and he was one game away from repeating in 2017 until UNC beat Gonzaga.

As for his Stony Brook effort, Moffitt plans to collaborate with members of the Cancer Center as well. “Being in demand is a good thing.”

Above, Ken Dill shows how molecules fold and bind together. Photo from SBU

By Daniel Dunaief

The raw materials were here. Somehow, billions of years ago, these materials followed patterns and repeated and revised the process, turning the parts into something more than a primordial soup.

Ken Dill, who is a distinguished professor and the director of the Laufer Center for Physical and Quantitative Biology at Stony Brook University, took a methodical approach to this fundamental development. He wanted to understand the early statistical mechanics that would allow molecules to form long chains, called polymers, which contained information worthy of being passed along. The process of forming these chains had to be self-sustaining.

After all, Dill said, many activities reach an end point. Putting salt in water, for example, creates a mixture, until it stops. Dill, however, was looking for a way to understand auto-catalytic or runaway events. Lighting a forest fire, for example, is much more self sustaining, although even it eventually stops. Life has continued for over four billion years.

On Aug. 22, Dill, Elizaveta Guseva and Ronald Zuckermann, the facility director in biological nanostructures at the Lawrence Berkeley National Laboratory, published a paper in the journal Proceedings of the National Academy of Sciences (PNAS).

The researchers developed a fold and catalyze computational model that would explain how these long chains developed in a self-sustaining way, in which hydrophilic and hydrophobic polymers fold and bind together.

Random sequence chains of each type can collapse and fold into structures that expose their hydrophobic parts. Like a conga line at a wedding reception, the parts can then couple together to form longer chains.

These random chemical processes could lead to pre-proteins. Today’s proteins, Dill said, mostly fold into a very particular shape. Pre-proteins would have been looser, with more shape shifting.

The workhorses of the body, proteins perform thousands of biochemical reactions. Dill suggested that this model “rates high on the list” in terms of the findings he’s made over the course of his career.

Zuckermann described this work as significant because it lays out predictions that can be tested. It highlights the importance of chemical sequence information in polymer chains and “how certain sequences are more likely to fold into enzyme-like shapes and act as catalysts than others,” he explained in an email.

Zuckermann works with substances he figured out how to make in a lab that are called peptoids, which are non-natural polymers. These peptoids are a “good system to test the universality of [Dill’s] predictions,” he said.

The “beauty” of Dill’s work, Zuckermann suggested, is that “it should apply to most any kind of polymer system” where researchers control the monomer sequence and include hydrophobic and hydrophilic monomers in a particular order, putting Dill’s predictions to the test.

For her part, Guseva worked in Dill’s lab for her PhD thesis. She had started her research on something that was “more standard physical biology” Dill said, but it “was not turning out to be particularly interesting.”

The scientists had a discussion about trying to develop a chemical model related to the origins of life. While exciting for the scope of the question, the research could have come up empty.

“There was so much potential to fail,” Dill said. “I feel pretty uncomfortable in general about asking a graduate student to go in that direction, but she was fearless.”

Dill and Zuckermann, who have collaborated for over 25 years, are trying to move forward to the next set of questions.

Zuckermann’s efforts will focus on finding catalytic peptoid sequences, which are nonbiological polymers. He will synthesize tens of thousands of peptoid sequences and rank them on how enzyme-like they are. This, he explained, will lead to a better understanding of which monomer sequences encode for protein-like structure and function.

Zuckermann suggested that the process in this research could have the effect of transforming a soup of monomers into a soup of functional polymers. This, he said, might set the stage for the evolution of DNA and RNA.

Proteins could have been a first step towards a genetic code, although life, as currently defined, would not have blossomed until a genetic code occurred, too, Dill suggested.

The origins of DNA, however, remains an unanswered question. “We’re trying to think about where the genetic code comes from,” Dill said. “It’s not built into our model per se. Why would biology want to do a two polymer solution, which is messy and complicated and why are proteins the functional molecules? This paper doesn’t answer that question.”

Dill and Zuckermann are in the early stage of exploring that question and Dill is hopeful he can get to a new model, although he doesn’t have it yet.

Dill moved from the University of California at San Francisco to join the Laufer Center about seven years ago. He appreciates the freedom to ask “blue sky questions” that he couldn’t address as much in his previous work.

Wearing a hat from his native Oklahoma, Dill, in a photo from around 1997, tinkers with a toy boat he made with sons Tyler and Ryan. Photo by Jolanda Schreurs

A resident of Port Jefferson, Dill lives with his wife Jolanda Schreurs, who has a PhD in pharmacology. The couple has two sons, Tyler and Ryan.

Tyler graduated with a PhD from the University of California at San Diego and now works for Illumina, a company which which makes DNA sequencers. Ryan, meanwhile, is earning his PhD in chemistry from the University of Colorado and is working on lasers.

“We didn’t try to drag our sons into science,” Dill said. “With both kids, however, we had a workshop in the basement” where they often took anything that was within arm’s reach and nailed it to a board. One of the finished products was a remote-controlled and motorized boat.

As for his lab work, Dill is thrilled to have this model that he, Guseva and Zuckermann provided, while he recognizes the questions ahead. Scientists “see something puzzling and, rather than saying, ‘I need to avoid this, I don’t have an answer,’ we find it intriguing and these things lead from one step to the next. There tends to remain a huge number of super fascinating problems.”

Alex Orlov on the campus of the University of Cambridge. Photo by Nathan Pitt, University of Cambridge

By Daniel Dunaief

The Ukranian-born Alex Orlov, who is an associate professor of materials science and chemical engineering at Stony Brook University, helps officials in a delicate balancing act.

Orlov, who is a member of the US-EU working group on Risk Assessment of Nanomaterials, helps measure, monitor and understand the hazards associated with nanoparticles, which regulatory bodies then compare to the benefit these particles have in consumer products.

“My research, which is highlighted by the European Union Commission, demonstrated that under certain conditions, [specific] nanoparticles might not be safe,” Orlov said via Skype from Cambridge, England, where he has been a visiting professor for the past four summers. For carbon nanotubes, which are used in products ranging from sports equipment to vehicles and batteries, those conditions include exposure to humidity and sunlight.

“Instead of banning and restricting their production” they can be reformulated to make them safer, he said.

Orlov described how chemical companies are conducting research to enhance the safety of their products. Globally, nanotechnology has become a growing industry, as electronics and drug companies search for ways to benefit from different physical properties that exist on a small scale. Long Island has become a focal point for research in this arena, particularly at the Center for Functional Nanomaterials and the National Synchrotron Light Source II at Brookhaven National Laboratory.

Alex Orlov on the campus of the University of Cambridge. Photo by Nathan Pitt, University of Cambridge

Indeed, Orlov is working at the University of Cambridge to facilitate partnerships between researchers in the chemistry departments of the two universities, while benefiting from the facilities at BNL. “We exchange some new materials between Cambridge and Stony Brook,” he said. “We use BNL to test those materials.”

BNL is an “essential facility,” Orlov said, and is where the postdoctoral student in his lab and the five graduate students spend 30 to 60 percent of their time. The data he and his team collect can help reduce risks related to the release of nanomaterials and create safer products, he suggested.

“Most hazardous materials on Earth can be handled in a safe way,” Orlov said. “Most scientific progress and environmental protection can be merged together. Understanding the environmental impact of new technologies and reducing their risks to the environment should be at the core of scientific and technological progress.”

According to Orlov, the European Union spends more money on technological safety than the United States. European regulations, however, affect American companies, especially those that export products to companies in the European Union.

Orlov has studied how quickly toxic materials might be released in the environment under different conditions.

“What we do in our lab is put numbers” on the amount of a substance released, he said, which informs a more quantitative understanding of the risks posed by a product. Regulators seek a balance between scientific progress and industrial development in the face of uncertainty related to new technologies.

As policy makers consider the economics of regulations, they weigh the estimated cost against that value. For example, if the cost of implementing a water treatment measure is $3 million and the cost of a human life is $7 million, it’s more economical to create a water treatment plan.

Orlov teaches a course in environmental engineering. “These are the types of things I discuss with students,” he said. “For them, it’s eye opening. They are engineers. They don’t deal with economics.”

In his own research, Orlov recently published an article in which he analyzed the potential use of concrete to remove pollutants like sulfur dioxide from the air. While concrete is the biggest material people produce by weight and volume, most of it is wasted when a building gets demolished. “What we discovered,” said Orlov, who published his work in the Journal of Chemical Engineering, “is that if you take this concrete and expose new surfaces, it takes in pollutants again.”

Fotis Sotiropoulos, the dean of the College of Engineering and Applied Sciences at SBU, said Orlov has added to the understanding of the potential benefits of using concrete to remove pollutants.

Other researchers have worked only with carbon dioxide, and there is “incomplete and/or even nonexistent data for other pollutants,” Sotiropoulos explained in an email. Orlov’s research could be helpful for city planners especially for end-of-life building demolition, Sotiropoulous continued. Manufacturers could take concrete from an old, crushed building and pass waste through this concrete in smokestacks.

To be sure, the production of concrete itself is energy intensive and generates pollutants like carbon dioxide and nitrogen dioxide. “It’s not the case that concrete would take as much [pollutants] out of the air as was emitted during production,” Orlov said. On balance, however, recycled concrete could prove useful not only in reducing waste but also in removing pollutants from the air.

Orlov urged an increase in the recycling of concrete, which varies in the amount that’s recycled. He has collaborated on other projects, such as using small amounts of gold to separate water, producing hydrogen that could be used in fuel cells.

“The research showed a promising way to produce clean hydrogen from water,” Sotiropoulos said.

As for his work at Cambridge, Orlov appreciates the value the scientists in the United Kingdom place on their collaboration with their Long Island partners.

“Cambridge faculty from disciplines ranging from archeology to chemistry are aware of the SBU/BNL faculty members and their research,” Orlov said. A resident of Smithtown, Orlov has been on Long Island for eight years. In his spare time, he enjoys hiking and exploring new areas. As for his work, Orlov hopes his work helps regulators make informed decisions that protect consumers while making scientific and technological advances possible.

From left, scientist Lin Yang at the LiX beamline demonstrates how the beam hits the sample to high school teachers James Ripka, Mary Kroll, Fred Feraco, Janet Kaczmarek and Jocelyn Handley-Pendleton. Photo from BNL

By Daniel Dunaief

He helped build it and now a range of researchers are coming.

Lin Yang helped create the LiX beamline at the National Synchrotron Light Source II at Brookhaven National Laboratory, which is attracting researchers eager to study the fine structure and function of everything from proteins to steel.

The lead scientist for the LiX beamline at the NSLS-II at BNL, Yang was the control account manager for the construction of the beamline and was the spokesperson for a team that wrote the original beamline development proposal.

“In our case, the scattering from the sample is sensitive to the underlying structure” of materials, Yang said. “That’s why people want to use scattering to study their samples.”

Like the other beamlines at the NSLS-II, the LiX enables scientists to use sophisticated equipment to search for links between structures and function. Each beamline has a three-letter acronym. In the case of LiX, the “Li” stands for life sciences, while the “X” represents X-ray scattering.

When they designed the beamline, LiX researchers were seeking optics that were capable of producing a beam to conform to the specifications required for different types of measurements. They then designed an experimental station that is suitable for handling biological samples. Specifically, that involved developing an automated sample handler for measurements on protein molecules in solution.

“With atomic resolution structures and functional assays, we do get new insights [about] important ions such as calcium,” which are involved in signaling and physiology, Qun Liu, a principal investigator in the Biology Department at BNL, described in an email. “LiX will be essential to allow us [to see] the transport process in real time and space.” Liu wrote that Yang is an “outstanding X-ray beamline scientist” who is also well known for his pioneering work on membrane diffraction.

The ability to perform measurements using a beam of a few microns is “pretty unique right now,” which also attracted researchers working with steel samples, Yang said. “When we designed the instrument, our focus [was] on the biological structure” but the beamline is “versatile enough” that it has found other uses, Yang said.

Researchers working with steel realized that the same diffraction-based approach to finding underlying structures in living tissue could also shed light on the structures of their samples.

In everyday life, diffraction is visible from the wavelengths of light that form the hologram on a credit card. Scientists working with steel have been applying for time on the LiX beamline, too, creating a competitive environment for researchers working in both fields.

Lynne Ecker, the deputy department chair in the Nuclear Science and Technology Department at Brookhaven National Laboratory, has used the beamline to study the effect of neutrons and ions on steel.

“Ions will only damage steel so far,” Ecker said. The LiX is “perfect” to study the degree of the damage. Ecker said she’s tried this kind of analysis in other places, but the LiX provides better spatial resolution. The LiX scientists are working on improving the degree of automation for sample handling and data processing.

“We are about to install a six-axis robot, which is typically seen in industrial automation, to help realize unattended overnight measurements on protein solution samples,” Yang said. The robot is already at the facility and Yang and his team will be installing the support structure to mount the robot in the experimental station this month. “The more challenging task is to put the software in place so that the beamline can control the robot,” he explained in an email.

The LiX beamline uses lenses made from beryllium, which are transparent to X-rays. For X-rays at the wavelength of about one angstrom, about 93 percent can pass through about a millimeter of beryllium. That compares favorably to aluminum, which allows about 2 percent to pass through at the same thickness.

The LiX beamline can run at 500 frames per second, which produces a wealth of data. In practice, it may take up to a second for the detector to accumulate enough signal from the sample. Still, the beamline can generate enough data that the experimenter may not be able to examine it frame by frame, which makes automated data processing more important.

Scientists have used the beamline to explore the structure of plants. These researchers mainly want to understand how materials like cellulose are organized within different parts of the plant and in different plants.

In bones, researchers can differentiate between organic matter like collagen and inorganic matter. Not only can they determine where they are, but they can also explore their orientation in a sample. Bones are easy samples since collagen and minerals in bone have distinctive scattering and diffraction patterns, Yang said. Researchers “like to look at how biological molecules change their shape as they interact with their functional partners,” Yang said.

A resident of East Setauket, Yang lives with his wife Mian Wang, who is an architect in Farmingdale, and their two daughters. A fan of tennis, Yang plays as often as he can during the summer at the Three Village Tennis Club.

Yang grew up in Yunnan province in the southwest of China. Trained as a physicist, Yang picked up knowledge of molecular biology from his years of working with other scientists. In his work, he gets to combine his talents in engineering, programming and molecular biology.

“We learn new things when we interact with our users/guest researchers since we first need to learn about their problems before we can help solve them,” he described in an email. Yang hopes the research he and the team at the LiX support will result in high-impact publications. “As more researchers know about us and our capabilities, I expect more people will want to perform experiments at our beamline,” he said.

Above, Alesi, the skull of the new extinct ape species Nyanzapithecus alesi. Photo by Fred Spoor

By Daniel Dunaief

They were in a terrible mood. They had spent an entire day searching for clues about creatures that walked the Earth millions of years ago and had come up empty.

“We were not finding even a single bone, nothing,” recalled Isaiah Nengo, who will be an associate director of the Turkana Basin Institute and an assistant research professor at Stony Brook University this fall.

Alesi after attached sandstone rock was partially removed at the Turkana Basin Institute, near Lodwar, Kenya. Photo by Christopher Kiarie

One of the fossil hunters in the group, John Ekusi, started rolling a cigarette. Nengo told him to move away from them so that they didn’t inhale second-hand smoke. Walking ahead, Ekusi made a spectacular discovery that Nengo called a “freak of a fossil.” Ekusi pointed out a bone sticking out of the ground that looked like the femur of a large animal. When they got closer, they could see that it had brow ridges. Pushing aside dirt, they saw the outline of a primate skull.

“We knew we had found something unique and we started celebrating right there,” Nengo said. “We were dancing and high-fiving. The thrill was unimaginable.”

Nengo and his team discovered the fossil on Sept. 4, 2014, in northern Kenya. This week, a team of researchers from the United States, France and England are unveiling three years worth of research into this remarkable find in the prestigious research journal Nature.

For starters, the researchers had to confirm the date of their fossil, which was about the size of a lemon. Rutgers University geologists Craig Feibel and Sara Mana studied the matrix around the fossil and the area around it.

Akai Ekes and John Ekusi watch as Isaiah Nengo lifts the sandstone block with Alesi after six hours of excavation. Photo from ​Isaiah Nengo

“There was no doubt that [the fossil] came from this deposit and hadn’t rolled in or washed in” during some later period, explained Ellen Miller, a professor of physical anthropology at Wake Forest University.

Next, they had to figure out what kind of primate they had: It could have been an ape or a monkey. Fred Spoor, a paleontologist at University College London, did an initial CT reading using a medical scanner. He found intact molars that were characteristic of apes.

The researchers wanted to do a more thorough analysis of the three-dimensional shape of the skull, so they called Paul Tafforeau, a paleoanthropologist specialist of X-ray imaging who works as a beamline scientist at the European Synchrotron Radiation Facility in Grenoble, France. Typically, such research centers require scientists to wait a year or more.

As soon as Tafforeau saw the photos, Nengo recalls, he said, “You can bring it in anytime.” Tafforeau used a technique called propagation phase contrast–X-ray synchrotron microtomography. In an email, Tafforeau described it as being close to a medical scanner, but 1,000 times more precise and sensitive.

Over the course of three or four days, Tafforeau analyzed the teeth that hadn’t erupted from this young primate, which indicated that this individual died when it was only 16 months old. The teeth also demonstrated that the toddler, whose gender is difficult to determine because of its age, belonged to a new species, called Nyanzapithecus alesi. The name Alesi comes from the Turkana word “ales,” which means ancestor.

Tafforeau said the thickness of the tooth enamel suggest a classic hominoid diet, which would be similar to that of a modern gibbon, and would consist mostly of fruits and leaves. Researchers estimate that an adult of this species would weigh about 20 pounds.

Turning their attention to the fantastic creature’s ears, the researchers found that it didn’t have a balance organ. That means it couldn’t move as rapidly through trees as a gibbon. The ears of this primate, however, did have fully developed bony ear tubes. These ear structures “absolutely confirmed that these were apes,” said Miller. “We had no specimens between 15 million and 10 million years ago.”

Field crew of the​ Stony Brook University-affiliated​ Turkana Basin Institute​ when Alesi​ ​was discovered​ ​at​ Napudet​ in September 2014. From​ ​left, Abdala Ekuon, John Ekus​i, Isaiah Nengo,​ ​Bernard Ewoi, Akai Ekes and Cyprian Nyete.​ Photo from Isaiah​ ​​​Nengo.

Scientists generally believe apes and humans diverged in their evolution about 7 million years ago. That means this toddler ape belongs to a species that is likely a common ancestor for other apes and humans.

Anthropologist Meave Leakey, a research professor in the Department of Anthropology and the Turkana Basin Institute, suggested that this fossil “gives us a picture for the first time of what the ancestor of apes and humans looked like 13 million years ago. It also suggests,” she continued in an email, “that the nyanzapiehecines were close to the origin of all living apes and humans.”

Leakey described the fossil as one of the most complete skulls of an ape ever found anywhere and indicated it was of an age that is poorly represented in the African fossil record.

The three years between the discovery of the fossil and its unveiling to the world in the Nature article is “actually very quick,” Leakey explained. The images captured through the synchrotron provide detailed pictures of structures that would otherwise be hidden by bone.

Gathering and interpreting these images meant traveling to Grenoble, which, she explained, “takes considerable time.”

Researchers involved in this study said this is just the beginning of the work they will conduct on this rare and detailed fossil. Nengo said they had already collected two terabytes worth of data from their scans. Much of the further study of this ape will involve a closer examination of all of that data.

“A paper coming out in Nature makes it seem like the end of the process,” Miller said. “This is just the beginning.” He is intrigued to learn more about the organization of the brain.

Nengo hopes to bring together researchers for a two- or three-day workshop in September or October at Stony Brook University to tackle the next phase of analysis for Alesi.

As it turns out, September will likely become an important anniversary for Nengo, as he recalls the memory of a day three years ago that didn’t start out particularly well, but that ended with a rare and thrilling fossil find.

Nengo recalled how excited he was to return to the Turkana Basin Institute to show Richard Leakey, the founder of the site, Meave Leakey and Lawrence Martin, the director of TBI. “I had photos on my iPad and they were absolutely thrilled,” said Nengo. “Everybody was beginning the guesswork of wondering what it is.”

Organizers of the 3rd annual Genome Engineering: The CRISPR-Cas Revolution event, from left, Maria Jasin, Jonathan Weissman, Jennifer Doudna and Stanley Qi. Photo courtesy of CSHL

By Daniel Dunaief

One day, the tool 375 people from 29 countries came to discuss in late July at Cold Spring Harbor Laboratory may help eradicate malaria, develop treatments for cancer and help understand the role various proteins play in turning on and off genes.

Eager to interact with colleagues about the technical advances and challenges, medical applications and model organisms, the participants in Cold Spring Harbor Laboratory’s third meeting on the CRISPR-Cas9 gene editing system filled the seats at Grace Auditorium.

Jason Sheltzer. Photo from CSHL

“It’s amazing all the ways that people are pushing the envelope with CRISPR-Cas9 technology,” said Jason Sheltzer, an independent fellow from Cold Spring Harbor Laboratory who presented his research on a breast cancer treatment.

The technology comes from a close study of the battle between bacteria and viruses. Constantly under assault from viruses bent on commandeering their genetic machinery, bacteria figured out a way of developing a memory of viruses, sending out enzymes that recognize and destroy familiar invaders.

By tapping into this evolutionary machinery, scientists have found that this system not only recognizes genes but can also be used to slice out and replace an errant code.

“This is a rapidly evolving field and we continue to see new research such as how Cas1 and Cas2 recognize their target, which opens the door for modification of the proteins themselves, and the recent discovery of anti-CRISPR proteins that decrease off-target effects by as much as a factor of four,” explained Jennifer Doudna, professor of chemistry and molecular and cell biology at the University of California at Berkeley and a meeting organizer for the last three years, in an email.

Austin Burt, a professor of evolutionary genetics at the Imperial College in London, has been working on ways to alter the genes of malaria-carrying mosquitoes, which cause over 430,000 deaths each year, primarily in Africa.

“To wipe out malaria would be a huge deal,” Bruce Conklin, a professor and senior investigator at the Gladstone Institute of Cardiovascular Disease at the University of California in San Francisco and a presenter at the conference, said in an interview. “It’s killed millions of people.”

Carolyn Brokowski. Photo by Eugene Brokowski

This approach is a part of an international effort called Target Malaria, which received support from the Bill and Melinda Gates Foundation.

To be sure, this effort needs considerable testing before scientists bring it to the field. “It is a promising approach but we must be mindful of the unintended consequences of altering species and impacting ecosystems,” Doudna cautioned.

In an email, Burt suggested that deploying CRISPR in mosquitoes across a country was “at least 10 years” away.

CSHL’s Sheltzer, meanwhile, used CRISPR to show that a drug treatment for breast cancer isn’t working as scientists had thought. Researchers believed a drug that inhibited the function of a protein called maternal embryonic leucine zipper kinase, or MELK, was halting the spread of cancer. When Sheltzer knocked out the gene for MELK, however, he discovered that breast cancer continued to grow or divide. While this doesn’t invalidate a drug that may be effective in halting cancer, it suggests that the mechanism researchers believed was involved was inaccurate.

Researchers recognize an array of unanswered questions. “It’s premature to tell just how predictable genome modification might be at certain levels in development and in certain kinds of diseases,” said Carolyn Brokowski, a bioethicist who will begin a position as research associate in the Emergency Medicine Department at the Yale School of Medicine next week. “In many cases, there is considerable uncertainty about the causal relationship between gene expression and modification.”

Brokowski suggested that policy makers need to appreciate the “serious reasons to consider limitations on nontherapeutic uses for CRISPR.”

Like so many other technologies, CRISPR presents opportunities to benefit mankind and to cause destruction. “We can’t be blind to the conditions in which we live,” said Brokowski.

Indeed, Doudna recently was one of seven recipients of a $65 million Defense Advanced Research Projects Agency award to improve the safety and accuracy of gene editing.

The funding, which is for $65 million over four years, supports a greater understanding of how gene editing technologies work and monitors health and security concerns for their intentional or accidental misuse. Doudna, who is credited with co-creating the CRISPR-Cas9 system with Emmanuelle Charpentier a scientific member and director of the Max Planck Institute for Infection Biology in Berlin, will explore safe gene editing tools to use in animal models and will specifically target Zika and Ebola viruses.

“Like most misunderstood disruptive technologies, CRISPR outpaced the necessary policy and regulatory discussions,” Doudna explained. The scientific community, however, “continued to advance the technology in a transparent manner, helping to build public awareness, trust and dialogue. As a result, CRISPR is becoming a mainstream topic and the public understanding that it can be a beneficial tool to help solve some of our most important challenges continues to grow.”

Visitors enjoyed a wine and cheese party on the Airslie lawn during the event. Photo from CSHL

Cold Spring Harbor Laboratory plans to host its fourth CRISPR meeting next August, when many of the same scientists hope to return. “It’s great that you can see how the field and scientific community as a whole is evolving,” Sheltzer said.

Doudna appreciates the history of Cold Spring Harbor Laboratory, including her own experiences. As a graduate student in 1987, Doudna came across an unassuming woman walking the campus in a tee-shirt: Nobel Prize winner Barbara McClintock. “I thought, ‘Oh my gosh, this is someone I revere,” Doudna recalled. “That’s what life is like” at the lab.

Brokowski also plans to attend the conference next year. “I’m very interested in learning about all the promises CRISPR will offer,” she said. She is curious to see “whether there might be more discussion about ethical and regulatory aspects of this technology.”

Michael Airola. Photo from SBU

By Daniel Dunaief

Numerous trucks arrive at a construction site, each doing their part to make a blueprint for a building into a reality. In a destructive way, molecules also come together in cancer to change cells that cause damage and can ultimately kill.

Researchers often know the participants in the cancer process, although the structure of each molecule can be a mystery. Determining how the parts of an enzyme work could allow scientists and, eventually, doctors to slow those cancer players down or inactivate them, stopping their cell-damaging or destroying processes.

Recently, Michael Airola, who started his own lab at Stony Brook University early this year and is an assistant professor of biochemistry and cell biology, published a paper in the Proceedings of the National Academy of Sciences in which he showed the structure of an important enzyme that contributes to cell growth regulation in cancer and other diseases, including Alzheimer’s disease.

Called neutral sphingomyelinase, this enzyme produces ceramide, which allows cancer cells to become metastatic. Finding the structure of an enzyme can enable scientists to figure out the way it operates, which can point to pharmacological agents that can inhibit or deactivate the enzyme.

“We are trying to understand the link between structure and function to try to get the first sort of snapshots or pictures of what these enzymes look like” in the on and off states, said Airola. In his research, he showed what this enzyme looked like in its off or inactive state.

Airola joined Stony Brook Cancer Center Director Yusuf Hannun’s lab as a postdoctoral researcher in 2010, when Hannun was working in Charleston, South Carolina, at the Medical University of South Carolina. When Hannun moved to SBU in March of 2012, Airola joined him, continuing his postdoctoral research.

Michael Airola in April in New Orleans aboard the steamboat Natchez on the Mississippi River with his family, wife Krystal Airola, four-year-old Harper and two-year-old Grady. Photo from Michael Airola

Airola conducted his research at Stony Brook and Brookhaven National Laboratory, where he used a technique called X-ray crystallography, which shows the structure of crystallized molecules. Getting this enzyme to crystallize took considerable effort, especially because it has what Airola described as a floppy segment between two rigid structures.

Those floppy pieces, which Airola said aren’t the active sites of the enzyme, can interfere with the structural analysis. To see the important regions, Airola had to cut those flexible parts out, while fusing the rest of the enzyme into a single structure.

The crystallization took almost three years and was a “very difficult process,” Airola recounted. “To get proteins to crystallize, you need to get them to pack together in an ordered fashion.” He said he needed to develop some biochemical tricks to delete a large part in the middle of the protein. “Once we found the right trick and the right region to delete, we were able to crystallize the protein in about three months.”

Airola said he took considerable care to make sure removing the floppy or flexible region didn’t disrupt the function of the enzyme. Hannun and Airola are co-mentoring Prajna Shanbhogue, a graduate student who is in the process of discovering molecules that activate and inhibit the enzyme.

Hannun was pleased with the work Airola did in his lab, which he suggested was a “challenging type of research. Getting to a structure of a protein or enzyme (a specific type of protein) can take several years and is never guaranteed of success, but the rewards can be tremendous,” Hannun explained in an email, adding that Airola was a “critical contributor” and introduced structural biology to his group.

While Airola will continue to work on this enzyme, he is exploring another enzyme, in a collaboration with Hannun and John Haley at Stony Brook, that is involved in colon cancer.

Airola, two graduate students and three undergraduates in his lab are focusing considerable energy on an enzyme involved in the production of triglycerides.

Airola recently received a three-year, $231,000 grant from the American Heart Association to study lipins, a class of enzyme that plays a role both in heart disease and in diabetes. As he did with the enzyme that makes ceramide, Airola is developing a way to understand the structure and function of the triglyceride enzyme. He’d like to find out how this enzyme is regulated. “We’re trying to see if we can inhibit that enzyme, too,” he said.

Airola has “some creative ideas about using information from lipin proteins in plants and fungi, which have a less complex protein structure than mammalian lipins but catalyze the same biochemical reaction,” Karen Reue, a professor in the Department of Human Genetics, David Geffen School of Medicine at UCLA and a collaborator with Airola, explained in an email.

Reue’s lab will complement Airola’s work by conducting physiological analyses of the various “minimal” lipin proteins in processes that the mammalian proteins perform, including triglyceride biosynthesis.

While lipin proteins are necessary for metabolic homeostasis, Reue said a reasonable but still challenging goal might be to modulate the enzyme’s activity for partial inhibition in areas such as adipose tissue, while allowing the triglycerides to perform other important tasks.

Airola lives in East Setauket with his wife Krystal Airola, who is doing her residency in radiology at SBU, and their two children, four-year-old Harper and two-year-old Grady. The couple, who is expecting a third child next month, enjoy living in East Setauket, where they appreciate that they have a forest in their backyard and they can enjoy the water in Port Jefferson and West Meadow Beach.

When Airola’s postdoctoral position ended, he did a broad, national search for his next position and was delighted that he could remain at Stony Brook. “We love the area,” he said. “The research and science here are fantastic.” Airola’s collaborators are optimistic about the prospects for his research.

He is an “up and coming structural biologist that has already made important contributions to the field of lipid biology” Reue said and is a “creative and rigorous scientist with a bright future.”

Alexander Krasnitz. Photo from CSHL

By Daniel Dunaief

If homeowners could find insects in their home, confirm that they were termites and locate nests before the termites damaged a house, they’d save themselves numerous problems. The same holds true for cancer.

Using the latest molecular biology techniques, researchers at Cold Spring Harbor Laboratory including Associate Professor Alexander Krasnitz and Professor Michael Wigler have explored ways to detect cancer earlier.

Unlike other scientists, who have created tests that reveal the genetic probability of developing cancer, Krasnitz and Wigler developed a blood test to reveal the presence of a tumor that might be hard to spot. Such a test could be particularly valuable for cancers such as ovarian and pancreatic cancer, which can be inoperable by the time they present clinical symptoms.

Urging what Wigler described as a “call to arms,” Krasnitz said they created a blood test, called copy number variation, that they hope will be economically feasible. In copy number variation, sections of genes are repeated. While healthy cells have copy number variation, cancer cells use them like a Jack Nicholson mantra in “The Shining,” where the repetition of “all work and no play makes Jack a dull boy” becomes a calling card for a killing spree.

In cancer, chromosomes or chromosome arms are duplicated or deleted. Sometimes, a narrow region of the genome undergoes amplification, creating multiple copies of the region. Other times, a region of the genome may be lost. Genome-wide copy number variation is a hallmark of cancer. Copy number variation occurs often amid the disruption of DNA repair mechanisms and the breakdown in the way DNA separates into daughter cells during division.

In a recent article in Trends in Molecular Medicine, Krasnitz, Jude Kendall, Joan Alexander, Dan Levy and Wigler — all scientists at CSHL — suggest the potential for single-cell genomic analysis that searches for the presence of copy number variations could raise the alert level for cancer, signaling the need to search more closely for developing tumors.

In most massive cancers in the population, including breast, ovarian and prostate cancer, copy number variation is “ubiquitous,” Krasnitz said. Screening for these changes could provide “evidence for the presence of something abnormal,” which can be validated through other tests, Krasnitz said.

Copy number variation, on its own, is not sufficient to detect cancer, Krasnitz said. Researchers need evidence of similar abnormal copy number profiles in multiple cells. For this test to have clinical relevance, it would need to minimize false positives, which could create alarm and lead to future tests that might not be warranted, while also avoiding false negatives, which would miss the presence of cancer.

The main sources of false positives could come from copy number variation that’s already in cells in the blood that randomly look like a tumor. Cells with partially degraded DNA can have high copy number variation, which the researchers have observed. These profiles, however, arise from random processes and typically look different from each other. Cells from a cancer clone, however, have similar copy number profile.

Cancers with low copy number variation were a minority among the 11 cancers the scientists studied and include a type of colorectal cancer called microsatellite-unstable. If these CSHL researchers developed a preclinical test, they would look for additional ways to detect such cancers.

While numerous technological innovations required for the test exist, including copy number profiling of single cells and methods to enrich specimens from blood for suspected tumors, Krasnitz explained that considerable work remains before its clinical use, including establishing tumor cell counts in the blood of early patients, making single-cell profiling cheaper and finding optimal ways to identify the tissue of origin.

They are planning to study newly diagnosed patients to observe the presence of circulating cells from tumors. Once the scientists prove that the test has some predictive value, they need to ensure that it is economical and that they can follow up with patients to find tumors.

At this point, it’s unclear what the presence of copy number variation might reveal about the type of tumor, which could be a slowly growing or an aggressive type. Additionally, an abnormal indication from this type of analysis wouldn’t reveal anything about the type of cancer. Further tests, including on RNA, would help direct doctors to a specific organ or system.

Apart from his work with Wigler, Krasnitz also has numerous collaborations, including one with CSHL Cancer Center Director David Tuveson.

In his work with Tuveson, Krasnitz is ensuring that the organoid models Tuveson’s lab creates, which are living replicas of tumors taken from patients, faithfully reflect the genetic make up of the tumors. That, Tuveson said, is a significant undertaking because it can validate the organoid model for exploring the biology of tumors.

“This is a deliverable that many people are waiting for,” Tuveson said. The researchers want to make sure “what we grew is what the patient had in the first place.” So far, Tuveson said, the data looks good and the scientists don’t have any examples of the genetics of the organoids differing from that of the tumor.

Krasnitz also attempts to predict an organoid’s response to drugs that haven’t been tested yet based on the organoid’s reaction to other drugs. Tuveson reached out to Krasnitz to work with his group. He said Krasnitz is “a major player” and is “very skilled” in the type of analysis of big data his group generates through the genome, the transcriptome and drug screens. “He’s able to look at those three types of information and make sense of it,” Tuveson said.

Krasnitz is grateful for the support of the Simons Foundation, the National Institutes of Health and the Breast Cancer Research Foundation for his work with Wigler. The most recent article with Wigler is an “invitation for the [research] community to join in the effort,” Krasnitz said. “We want collaborators and more competition in this area.”

Elizabeth Boon, back row, center, with graduate students from her lab at Stony Brook University. Photo from Elizabeth Boon

By Daniel Dunaief

It was in the back of Elizabeth Boon’s mind for the last decade. How, she wondered, could the switch that is so critical to life not be there and yet still allow for normal functioning? She suspected that there had to be another switch, so the associate professor in the Department of Chemistry at Stony Brook University, spent the last five years looking for it.

Sure enough, she and graduate students including Sajjad Hossain, found it.

Bacteria, like so many other living creatures, need to have a way of detecting nitric oxide gas. At a high enough concentration, this gas can kill them and, indeed, can kill other living creatures as well, including humans.

Nitric oxide is “toxic to any organism at a high enough concentration,” Boon said. “Most organisms have ways of detecting high concentrations … to avoid toxic consequences.” Other research had found a way other bacteria detect this toxic gas through a system called H-NOX, for heme nitric oxide/ oxygen binding protein.

When bacteria live together in colonies called biofilms, many of them typically rely on a signal about the presence of nitric oxide from the H-NOX protein. And yet, some bacteria survived without this seemingly critical protein. “We and others have shown that H-NOX detection of nitric oxide allows bacteria to regulate biofilm formation,” Boon explained.

Elizabeth Boon with her family, from left, Sheridan, 3, Cannon, 7, Beckett, 1, with her husband Isaac Carrico, who is also an Associate Professor in the Chemistry Department at Stony Brook University. Photo by Alfreda James

Named the nitric oxide sensing protein, or NosP, Boon and her team discovered this alternative signaling system that has some of the same functional group as the original mechanism. When activated in one bacteria, the Pseudomonas aeruginosa, this signaling mechanism causes biofilm bacteria to react in the same way as they would when an H-NOX system was alerted, by breaking up the colony into individuals. Using a flagella, an individual bacteria can move to try to escape from an environment containing the toxic gas.

Nicole Sampson, a professor of chemistry at Stony Brook University, suggested that this work was groundbreaking. While some biofilms are benign or even beneficial to humans, including a biofilm in the human gut, many of them, including those involved in hospital-borne infections, can cause illness or exacerbate diseases, particularly for people who are immunocompromised. Bacteria in biofilm are difficult to eradicate through drugs or antibiotics. When they are separated into individuals, however, they don’t have the same rigid defenses.

“They are resistant to most forms of treatment” when they are in biofilms, Boon said. “If we could get the bacteria to disperse, it’d be much easier to kill them. One of the hopes is that we could develop some sort of molecule that might loosen up the film and then we could come in with an antibiotic and kill the bacteria.”

Boon and her team published their results on the cover of the magazine ACS Infectious Disease, where they presented evidence of what they describe as a novel nitric oxide response pathway that regulates biofilm in the bacteria P. aeruginosa, which lack the H-NOX gene. The day the lab discovered this other protein, they celebrated with a trip for frozen yogurt at Sweet Frog.

In an email, Sampson said that finding the mechanism through which bacteria responds to nitric oxide “is important for developing therapies that target biofilms.”

While Boon is pleased that her lab found an alternative nitric oxide signaling system that answered a long-standing question about how some bacteria could respond to an environmental signal that suggested a threat to the biofilm, she said the answer to the question, as so many others do in the world of science, has led to numerous other questions.

For starters, the lab doesn’t yet know the structure of the NosP. “Not all proteins are immediately willing to crystallize,” Boon said. “We’re hopeful we’ll have a structure soon.” She knows it has a heme group, which includes an iron ion in the middle of an organic compound. That’s where the nitric oxide binds.

“We’d like to have the structure to piece together how that signal is relayed out to the end of the protein and how that gets transferred to other proteins that cause changes in behavior,” she said. The NosP is longer than the H-NOX protein, although they appear to have the same function.

Boon has also found that some bacteria have both the H-NOX and the NosP, which raises questions about why there might be an apparent redundancy. In organisms that have both proteins, it’s tempting to conclude that these bacteria live in a broader range of environments, which might suggest that the two systems react to the gas under different conditions. At this point, however, it’s too early to conclude that the additional sensing system developed to enable the bacteria to respond in a wider range of conditions.

Boon believes the nitric oxide system could be a master regulator of bacterial biofilms. “Detecting nitric oxide might be one of the first things that happen” to protect a bacteria, she said. The reason for that is that bacteria, like humans, use iron proteins in respiration. If those proteins are blocked by nitric oxide, any organism could suffocate.

Boon believes a multistep therapeutic approach might work down the road. She believes breaking up the biofilm would be an important first step in making the bacteria vulnerable to attack by antibiotics. She and her graduate students work with bacteria in the lab that generally only cause human disease in people who are already immunocompromised. Even so, her staff takes safety precautions, including working in a hood and wearing protective equipment.

Boon and her husband Isaac Carrico, who is an associate professor in the Department of Chemistry at Stony Brook University, have a 7-year-old son Cannon, a 3-year-old daughter Sheridan and a 1-year-old son Beckett. Boon said she and her husband are equal partners in raising their three children.

In her work, Boon is excited by the possibility of addressing new questions in this nitric oxide mechanism. “We’re trying to cover as much ground as fast as possible,” she said.

Standing near one of the X-ray scattering instruments, Kevin Yager holds a collection of samples, including a self-assembling polymer film. Photo courtesy of BNL

By Daniel Dunaief

Throw a batch of LEGOs in a closed container and shake it up. When the lid is opened, the LEGOs will likely be spread out randomly across the container, with pieces facing different directions. Chances are few, if any, of the pieces will stick together. Attaching strong magnets to those pieces could change the result, with some of the LEGOs binding together. On a much smaller scale and with pieces made from other parts, this is what researchers who study the world of self-assembled materials do.

Scientists at the Center for Functional Nanomaterials and at the National Synchrotron Light Source II at Brookhaven National Laboratory experiment with small parts that will come together in particular ways based on their energy landscapes through a process called self-assembly.

Every so often, however, a combination of steps will alter the pathway through the energy landscape, causing molecules to end up in a different final configuration. For many scientists, these so-called nonequilibrium states are a nuisance.

Above, Kevin Yager listens to sonified data. When data is sonified, it is translated into sound. Photo by Margaret Schedel

For Kevin Yager, they are an opportunity. A group leader at the CFN who works closely with the NSLS-II, the McGill University-educated Yager wants to understand how the order of these steps can change the final self-assembled product. “In the energy landscape, you have these peaks and valleys and you can take advantage of that to move into a particular state you want,” Yager said. “The high level goal is that, if we understand the fundamentals well enough, we can have a set of design rules for any structure we can dream up.”

At the CFN, Yager manages a nanofabrication facility that uses electron-beam lithography and other techniques to make nanostructures. He would like to fabricate model batteries to show the power of nanomaterials. He is also determined to understand the rules of the road in the self-assembly process, creating the equivalent of an instruction manual for miniature parts.

In future years, this awareness of nonequilibrium self-assembly may lead to revolutionary innovations, enabling the manufacture of parts for electronics, drugs to treat disease and deliver medicine to specific locations in a cell and monitors for the detection of traces of radioactivity or toxins in the environment, among many other possibilities.

Yager’s colleagues saw considerable opportunities for advancement from his work. Nonequilibrium self-assembly has “significant potential for a broad range of nanodevices and materials due to its ability to create complex structures with ease,” Oleg Gang, a group leader in Soft and Bio Nanomaterials at the CFN, explained in an email. Yager is an “excellent scientist” who produces “outstanding results.”

One of the things Yager hopes his research can develop is a way to “trick self-assembly into making structures they don’t natively want to make” by using the order of steps to control the final result.

As an example, Yager said he developed a sequence of steps in which nanoscale cylinders pack hexagonal lattices into a plane. These lattices tend to point in random directions as the cylinders form. By following several steps, including sheer aligning a plane and then thermal processing, the cylinders flip from horizontal to vertical as they inherit the alignment of the sheered surface. Flipping these cylinders, in turn, causes the hexagons all to point in the same direction. When Yager conducted these steps in a different order, he produced a different structure.

Broadly speaking, Yager is working on stacking self-assembling layers. In his case, however, the layers aren’t like turkey and swiss cheese on a sandwich, in which the order is irrelevant to the desired final product. Each layer has a hand in directing the way the subsequent layers stack themselves. Choosing the sequence in which he stacks the materials controls their structure.

Yager is working with Esther Takeuchi and Amy Marschilok at Stony Brook University to develop an understanding of the nanostructure of batteries. Gang suggested that Yager’s expertise is “invaluable for many scientists who are coming to the CFN to characterize nanomaterials using synchtrotron methods. In many cases, it would probably be impossible to achieve such quantitative understanding without [Yager’s] input.”

Yager and his wife Margaret Schedel, an associate professor in the Department of Music at Stony Brook University who is a cellist and a composer, live in East Setauket. The couple combined their talents when they sought ways to turn the data produced by the CFN, the NSLS and the NSLS-II into sound.

Scientists typically convert their information into visual images, but there’s “no reason we can’t do that with sound,” Yager said. “When you listen to data, you sometimes pick up features you wouldn’t have seen.”

One of the benefits of turning the data into sound is that researchers can work on something else and listen to the collection of data in the background, he said. If anything unexpected happens, or there is a problem with a sample or piece of equipment, they might hear it and take measures more rapidly to correct the process. “This started as a fun collaboration,” Yager said, “but it is useful.”

Schedel is working on sonifying penguin data as well. She also sonified wave data on Long Island. “By listening to the tides quickly, larger patterns emerge,” she said, adding that Yager thought the idea was theoretically interesting until he listened to misaligned data and then he recognized its benefit.

Schedel’s goal is to see this sonification effort spread from one beamline to all of them and then to the Fermilab near Chicago and elsewhere. She wants sonification to become “an ear worm in the science community.”

While Schedel introduced Yager to the world of sound in his research, he introduced her to sailing, an activity he enjoyed while growing up in the suburbs of Montreal. When she sails with him, they are “half in and half out of the boat,” Schedel said. It’s like two people “flying a kite, but you are the kite. You have to learn how to counterbalance” the boat. They hike out so they can take turns faster without tipping over, she said.

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