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Maggie Sullivan (Kevin Coughlin/Brookhaven National Laboratory)

Maggie Sullivan, an experienced leader and manager of the Talent Management group at the U.S. Department of Energy’s Brookhaven National Laboratory, was recently named Chief Human Resources Officer and Assistant Laboratory Director for Human Resources. Sullivan took over the position from Bob Lincoln, who transitioned to an advisory role after serving more than 12 years in the position.

Since joining the Lab in 2011, Sullivan has progressively assumed more responsibility, most recently leading a multidisciplinary team of HR professionals and administrators in training, recruitment, leadership development, and HR systems.

“Throughout her 12 years at Brookhaven, Maggie has demonstrated a strong ability to work with constituents across the Laboratory and to appreciate the role that each member of the Lab community plays in achieving our mission,” said Laboratory Director JoAnne Hewett. “She has also worked closely with senior leadership on major Lab initiatives and institutional-level processes, giving her insight into how the Lab and its senior leadership team operate.”

Sullivan has implemented best-in-class leadership development programs, including mentoring, the Lab’s Science and Engineering Development Program, and LEADER program for supervisory development. Most recently, she co-led the multi-year effort to modernize the Lab’s human capital management system. Sullivan has also served as the co-leader of the Lab’s recent engagement survey and continues to support that effort. Sullivan has also played a lead role in the design and delivery of supervisory and leadership training programs across the Battelle laboratory complex.

Sullivan partners closely with Brookhaven’s Chief Diversity Officer to promote a diverse, equitable, and inclusive work culture and is a key contributor to the Lab’s annual diversity, equity, and inclusion (DEI) plan. She is also a member of the Lab’s Executive DEI Council and the DEI Management Council, and she serves on the Human Resources Diversity, Equity, and Inclusion Council.

“I’m excited and looking forward to working closely with Lab leadership and staff as we continue to build our future workforce, advance DEI efforts, and review and modernize our HR processes and functions to best serve the Laboratory and our current and future staff,” said Sullivan. “We have a very talented HR team in place, and together we will create positive change for the Lab.”

Prior to her current role, the Hampton Bays resident was the Lab’s learning and development manager from 2011 to 2017. From 1989 to 2011, she worked for the Applied Research Corporation in Metuchen, NJ, first as a consultant, then senior consultant, then executive vice president.

Brookhaven National Laboratory is supported by the Office of Science of the U.S. Department of Energy. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit science.energy.gov.

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Dima Kozakov. Photo from SBU
Michael Zingale. Photo by John Griffin/SBU

By Daniel Dunaief

They have little in common. One studies deep inside cells to understand the difference between diseased and healthy states. The other explores models that represent distant thermonuclear reactions.

What Stony Brook University’s Dima Kozakov, Professor in the Department of Applied Mathematics and Statistics, and Michael Zingale, Professor in the Department of Physics and Astronomy, share, however, is that both led teams that recently won a Department of Energy grant that will allow them to use the fastest publicly available supercomputer in the world, at DOE’s Oak Argonne and Oak Ridge National Laboratories.

Kozakov and Zingale, who are both members of the Institute for Advanced Computational Sciences, are recipients of the DOE’s grants through its Innovative and Novel Computational Impact on Theory and Experiment (INCITE) program.

“It’s a huge recognition of computation” not just at the IACS, but also for Stony Brook in general, said Robert Harrison, Director of the IACS and Professor in the Department of Mathematics & Statistics. Kozakov and Zingale are the “point persons on world-class teams [which] positions Stony Brook at the forefront of the scientific community.”

Harrison suggested that the astrophysics group at Stony Brook was already world class when he arrived a decade ago and the university has been pushing to move Stony Brook to take advantage of all the modern powerful tools for simulation and data driven discovery.

Disease states

Kozakov, who is also an affiliate of the Laufer Center for Physical and Quantitative Biology,  plans to model enormous numbers of molecular interactions to compare how they function in diseased cells with how they work in healthy cells.

He and his team will get the data on important proteins and interactions in disease compared with healthy cells from high throughput but noisy experiments and validate those computationally.

By studying diseases such as cancer, diabetes and Alzheimer’s, Kozakov plans to look for clues about what occurs at the level of the atomic structure of protein interactions, hoping such an analysis points to the creation of new types of therapies.

Kozakov will use a combination of publicly available data and information from some of his experimental collaborators to identify new targets that small molecules may alter amid a diseased state. He feels the tight integration between the theoretical and the experimental nature of the team will enhance its effectiveness.

A supercomputer “allows you to try many approaches in parallel” such as training deep learning models that require trying many options to get the best possible ones, he said.

The pilot work the team has done created the kind of momentum that increased the chance of securing funds and time through the INCITE program.

Kozakov and co-investigators including Assistant Professor Pawel Polak at Stony Brook, Professor Andrew Emili at OHSU, Associate Professor Matthew Torres at Georgia Tech and Julie Mitchell, the Director of Biosciences Division at Oak Ridge National Laboratory, were “very happy” when they learned they’d won the award. he said. “It’s good to know that people appreciate the [work] we are doing.”

Starry, starry explosion

In the meantime, Zingale’s project, called “Exascale Models of Astrophysical Thermonuclear Explosions,” was renewed for a second year in the INCITE program.

Zingale leads a team that explores two types of astrophysical thermonuclear explosions to understand these physical processes and their broader implications. The computational work is focused mostly on whether a particular model for a thermonuclear explosion is viable.

“We really want to just understand: does it explode or not?” Zingale explained. His work focuses on the explosion mechanism and on the design of algorithms that can efficiently model these explosions.

Graduate students Zhi Chen, Alexander Smith Clark, Eric Johnson, Melissa Rasmussen, and Khanak Bhargava will be working with the supercomputer in the next year, Zingale added.

“Each student is working on separate questions, both on this problem and on related problems (novae and x-ray bursts),” said Zingale. “The goals are the same — in each case, we want to produce a realistic model of the burning that takes place in these events to understand how these explosions unfold.”

Models help connect to the observations astronomers make. While the work doesn’t produce new physics, it allows researchers to gain a greater understanding of supernovae.

Numerous other groups around the world are pursuing similar simulations, which Zingale explained is favorable for the science.

“If we all get the same result using different codes and techniques, then it gives us confidence that we might be understanding what is actually taking place in nature,” he said.

The explosions Zingale is studying differ from those on Earth because they are far larger and can reach higher densities in stars, which produces elements up to iron in explosions. The tools he uses to model these explosions have “similarities to the techniques used to model chemical combustion on Earth,” he said. “We work with applied mathematicians that study terrestrial flames and can use the techniques” in the astrophysical setting.

Zingale explained that he was always interested in astronomy and computers, so this field of work serves as the bridge between the two.

For students interested in the field, Zingale added that it teaches people how to solve complex problems on computers.

“Even if you don’t stay in the field, you build skills that are transferable to industry (which is where many of my graduate students wind up),” he said. He urges people to study something they enjoy. The main code he uses is called Castro and is freely available online, which means that “anyone can look at what we’ve done and run it for themselves,” he explained.

Student opportunities

For Stony Brook graduate students, these INCITE awards offer opportunities for additional learning and career advancement.

“The excitement is infectious,” said Harrison. “The students see not just the possibility to be at the frontier of discovery and the frontier of technology [but also to have] the career opportunities that lie beyond that.”

Students trained to make effective use of these platforms of cutting-edge science are “heavily recruited, going into industry, national labs, working for the likes of Google and so on,” Harrison added.

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Dr. Alexander Orlov. Photo by John Griffin/SBU

Alexander Orlov, PhD, Professor of Materials Science and Chemical Engineering at Stony Brook University, has been elected chair of the American Chemical Society’s (ACS) Environmental Division. With a four-year term starting January 1, 2024, Orlov will lead the Division’s extensive community of scientists toward the goal of applying concepts in chemistry to address the world’s leading environmental and sustainability issues.

Orlov, a Middle Island resident and professor at Stony Brook since 2008, has contributed significantly to environmental protection and sustainability efforts throughout his career. His work as an educator earned him the 2017 ACS Award for Incorporating Sustainability into Chemistry Education and the 2018 American Institute of Chemical Engineers Sustainable Engineering Forum Education Award. He is a member of the US-EU working group on Risk Assessment of Nanomaterials supported by the U.S. White House and European Commission cooperative program on nanotechnology research. In 2022, he was a chair of the Environmental Division at the American Institute of Chemical Engineers.

For years Orlov has contributed to the United Nations Environmental Program and has helped lead several reports coming out of the program. From 2007 to 2014, he was appointed by two UK Secretary of States to advise the government on environmental issues such as hazardous substances and environmental impact of nanotechnology.

Orlov’s interdisciplinary research seeks to develop new materials for clean energy generation, structural applications, and environmental protection. He currently co-directs two Centers at Stony Brook — the Center for Laser Assisted Advanced Manufacturing and the Center for Development and Validation of Scalable Methods for Sustainable Plastic Synthesis and Processing.

At more than 150,000 members, the ACS is one of the largest scientific societies in the U. S. Approximately 3,000 scientists nationally and internationally are in the Environmental Division. The Division is dedicated to addressing all 17 Sustainable Development Goals outlined by the United Nations with an emphasis on issues surrounding climate change.

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Photo courtesy of SBU

By Daniel Dunaief

Predicting extreme heat events is at least as important as tracking the strength and duration of approaching hurricanes.

Ping Liu

Extreme heat waves, which have become increasingly common and prevalent in the western continental United States and in Europe, can have devastating impacts through wildfires, crop failures and human casualties.

Indeed, in 2003, extreme heat in Europe caused over 70,000 deaths, which was the largest number of deaths from heat in recent years.

Recently, a trio of scientists at Stony Brook University’s School of Marine and Atmospheric Sciences (SoMAS) received $500,000 from the National Oceanographic and Atmospheric Administration to study heat events by using and analyzing NOAA’s Seamless System for Prediction and EArth System Research, or SPEAR, to understand heat waves and predict future such events.

The first objective is to evaluate simulations in the SPEAR model, by looking at how effectively this program predicts the frequency and duration of heat events from previous decades, said Ping Liu, who is the Principal Investigator on the project and is an Associate Professor at SoMAS.

Liu was particularly pleased to receive this funding because of the “urgent need” for this research, he explained in an email.

The team will explore the impact of three scenarios for increases in overall average temperature from pre-Industrial Revolution levels, including increases of 1.5 degrees Celsius, 2 degrees Celsius and four degrees Celsius, which are the increases the IPCC Assessment Reports has adopted.

Answering questions related to predicting future heat waves requires high-resolution modeling products, preferably in a large ensemble of simulations from multiple models, for robustness and the estimation of uncertainties, the researchers explained in their proposal.

“Our evaluations and research will provide recommendations for improving the SPEAR to simulate the Earth system, supporting NOAA’s mission of ‘Science, Service and Stewardship,’” they explained.

Kevin Reed, Professor, and Levi Silvers, research scientist, are joining Liu in this effort.

Liu and Reed recently published a paper in the Journal of Climate and have conducted unfunded research on two other projects. Liu brought Silvers into the group after Reed recommended Silvers for his background in climate modeling and dynamics.

Reed, who is Interim Director of Academic, Research and Commercialization Programs for The New York Climate Exchange, suggested that the research the heat wave team does will help understand the limitations of the SPEAR system “so that we can better interpret how the modeling system will project [how] blocking events and heat will be impacted by climate change.”

An expert in hurricanes, Reed added that blocking events, which can cause high pressure systems to stall and lead to prolonged heat waves, can also lead to unique hurricane tracks, such as Hurricane Sandy in 2012.

“A longer term goal of many of my colleagues at Stony Brook University is to better understand these connections,” said Reed, who is Associate Provost for Climate and Sustainability Programming and was also recently appointed to the National Academies’ Board on Atmospheric Sciences and Climate.

Liu will use some of the NOAA funds to recruit and train a graduate student, who will work in his lab and will collaborate with Reed and Silvers.In the bigger picture, the Stony Brook researchers secured the NOAA backing in the same year that the university won the bidding to develop a climate solutions center on Governors Island.

Reed suggested that the “results of the work can be shared with our partners and can help to inform future societally relevant climate research projects.”

Focus on two regions

The systems that have caused an increase in heat waves in the United States and Europe are part of a trend that will continue amid an uneven distribution of extreme weather, Liu added.

Heat waves are becoming more frequent and severe, though the magnitude and impact area vary by year, Liu explained.

The high pressure systems look like ridges on weather maps, which travel from west to east.

Any slowing of the system, which can also occur over Long Island, can cause sustained and uncomfortable conditions.

Over the past several years, Liu developed computer algorithms to detect high pressure systems when they become stationary. He published those algorithms in two journal papers, which he will use in this project.

Personal history

Born and raised in Sichuan, China, Liu moved to Stony Brook from Hawaii, where he was a scientific computer programmer, in November of 2009.

He and his wife Suqiong Li live in East Setauket with their 16-year old daughter Mia, who is a student at Ward Melville High School and  a pianist who has received classical training at the Manhattan School of Music. Mia has been trained by award-winning teacher Miyoko Lotto.

Outside of the lab, Liu, who is five-feet, seven-inches tall, enjoys playing basketball on Thursday nights with a senior basketball team.

Growing up in China, Liu was always interested in weather phenomenon. When he was earning his PhD in China at the Institute for Atmospheric Physics at the Chinese Academy of Sciences in Beijing, he had limited computer resources, working in groups with IBM and, at times, Dell computer. He built several servers out of PC parts.

With air trapped inside the basin surrounded by tall mountains, Sichuan is particularly hot in the summer, which motivated him to pursue the study of heat waves.

Liu appreciated how Stony Brook and Brookhaven National Laboratory had created BlueGene, which he used when he arrived.

As for the future of his work, Liu believes predicting extreme heat waves is increasingly important “to help planners from local to federal levels cope with a climate that is changing rapidly and fostering more frequent and more severe heat events,” he explained.

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Zhe Qian

By Daniel Dunaief

Addition and subtraction aren’t just important during elementary school math class or to help prepare tax returns.

As it turns out, they are also important in the molecular biological world of healthy or diseased cells.

Some diseases add or subtract methyl groups, with a chemical formula of CH3, or phosphate groups, which has a phosphorous molecule attached to four oxygen molecules.

Nicholas Tonks. Photo courtesy of CSHL

Adding or taking away these groups can contribute to the progression of a disease that can mean the difference between sitting comfortably and watching a child’s performance of The Wizard of Oz or sitting in a hospital oncology unit, waiting for treatment for cancer.

Given the importance of these units, which can affect the function of cells, researchers have spent considerable time studying enzymes such as kinases, which add phosphates to proteins.

Protein tyrosine phosphatases, which Professor Nicholas Tonks at Cold Spring Harbor Laboratory purified when he was a postdoctoral researcher, removes these phosphate groups.

Recent PhD graduate Zhe Qian, who conducted research for six years in Tonks’s lab while a student at Stony Brook University, published a paper in the journal Genes & Development demonstrating how an antibody that interferes with a specific type of protein tyrosine phosphatase called PTPRD alters the way breast cancer spreads in cell cultures.

“The PTPs are important regulators of the process of signal transduction — the mechanisms by which cells respond to changes in their environment,” explained Tonks. “Disruption of these signal transduction mechanisms frequently underlies human disease.”

To be sure, Tonks cautioned that the study, which provides a proof of concept for the use of antibodies to manipulate signaling output in a cancer cell, is a long way from providing another tool to combat the development or spread of breast cancer.

The research, which formed the basis for Qian’s PhD project, offers an encouraging start on which to add more information.

Blocking the receptor

Qian, who goes by the name “Changer,” suggested that developing a compound or small molecule to inhibit or target the receptor for this enzyme was difficult, which is “why we chose to use an antibody-based method,” he said.

By tying up a receptor on the outside of the cell membrane, the antibody also doesn’t need to enter the cell to reach its target.

The Antibody Shared Resource, led by Research Associate Professor Johannes Yeh, created antibodies to this particular receptor. Yeh created an antibody is shaped like a Y, with two arms with specific attachments for the PTPD receptor.

Once the antibody attaches, it grabs two of these receptors at the same time, causing a dimerization of the protein. Binding to these proteins causes them to lose their functionality and, ultimately, destroys them.

Cell cultures of breast cancer treated with this antibody became less invasive.

Limited presence

One of the potential complications of finding a new target for any treatment is the side effects from such an approach.

If, for example, these receptors also had normal metabolic functions in a healthy cell, inhibiting or killing those receptors could create problematic side effect.

In this case, however,  the targeted receptor is expressed in the spine and the brain. Antibodies normally don’t cross the blood-brain barrier.

Qian and Tonks don’t know if the antibody would affect the normal function of the brain. Further research would help address this and other questions.

Additionally, as with any possible treatment, future research would also need to address whether cancer cells developed resistance to such an approach.

In the time frame Qian explored, the cells in culture didn’t become resistant.

If the potential therapeutic use of this antibody becomes viable, future researchers and clinicians might combine several treatments to develop ways to contain breast cancer.

Eureka moment

In his research, Qian studied the effect of these antibodies on fixed cell, which are dead but still have the biochemical features of a living cell He also studied living cells.

When the antibody attaches to the receptor, it becomes visible through a staining process. Most antibody candidates stain living cells. Only the successful one showed loss-of-signal in living staining.

The antibody Qian used not only limited the ability of the receptor to send a signal, but also killed the receptor. The important moment in his research occurred when he discovered the antibody suppressed cancer cell invasion in cell culture.

Outside of the lab, Qian enjoys swimming, which he does between four and five times per week. Indeed, he combined his athletic and professional pursuits when he recently raised funds for Swim Across America.

“I not only want to do research, but I also want to call more attention to cancer research in the public,” said Qian.

The Swim Across America slogan suggests that each stroke is for someone who “couldn’t be with us” because of cancer. In the lab, Qian thinks each time he pipettes liquids during one of his many experiments it is for someone who couldn’t make it as well.

Qian, who currently lives in Hicksville, grew up in Suchow City, which is a village west of Shanghai and where Cold Spring Harbor Asia is located. 

Qian has been living on Long Island since he arrived in the United States. Qian graduated from Stony Brook University in October and is currently looking for a job in industry.

Looking back, Qian is pleased with the work he’s done and the contribution he’s made to breast cancer research. He believes the antibody approach offers a viable alternative or complement to searching for small molecules that could target or inhibit proteins or enzymes important in the development of cancer.

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These are C. albicans cells growing invasively into tissue in a mouse model of an oral infection. The candida hyphae are stained black, and the tissue is stained a blue/green. Photo by James Konopka

A study that assesses the effects of hypochlorous acid (HOCI), commonly known as bleach, as it is generated during the immune response of a cell (phagocytosis) when fighting a common fungal pathogen, Candida albicans, reveals that HOCI is a potent killing agent. The laboratory finding, highlighted in a paper published in the coming issue of the American Society of Microbiology’s mBio, also uncovers some of HOCI’s mechanisms of actions in that killing process. The work could be a significant step toward using HOCI as a novel therapeutic strategy against C. albicans, and potentially other pathogens.

C albicans causes much infection worldwide. It is particularly virulent in immunocompromised patients and the cause of dangerous systemic infections in this population. There have been many effective treatments against the fungal pathogen, but for decades drug resistance has been problematic when treating infections cause by C. albicans.

Most studies looking at this immune response against the fungal pathogen have focused on hydrogen peroxide (H2O2), not HOCI. Phagocytes capture the fungal invader and in the process two oxidants are created – H202 and HOCI. Myeloperoxidase converts H2O2 created during the oxidative burst in the phagosome into HOCI, the more potent killing agent.

“We discovered that hypochlorous acid kills cells by targeting the plasma membrane and oxidizing cellular components in a very different way than hydrogen peroxide,” says James Konopka, PhD, lead author and Professor in the Department of Microbiology and Immunology in the Renaissance School of Medicine at Stony Brook University. “It disrupts the C. albicans plasma membrane, produces a very different transcriptional response than hydrogen peroxide, is more effective and disruptive to the plasma membrane, and therefore has a more distinct effect on killing these fungal cells.”

Konopka explains that neutrophils are the critical cell type for controlling infections by C. albicans and other fungal pathogens. They are distinct because they make high levels of myeloperoxidase compared to other phagocytes, such as macrophages. This study shows the important aspect of the neutrophil response, essential to the oxidative process that produces this fungal killing HOCI or bleach.

While the laboratory results will not have any immediate impact on new treatments against C. albicans infections,  Konopka believes the findings provide a basis for designing new therapeutic strategies against this pathogen that causes infections worldwide.

The research was supported by a grant from the National Institutes of Health’s Institute of Allergies and Infectious Disease (grant number RO1AI047837), and in collaboration with researchers at Seoul National University in South Korea.

 

 

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The 2023 Double Helix Medals Dinner was once again held under the American Museum of Natural History's iconic blue whale model. Photo from CSHL

By Nick Wurm

On November 15, Cold Spring Harbor Laboratory (CSHL) held its 18th annual Double Helix Medals dinner (DHMD) at the American Museum of Natural History in New York City. CBS journalist Lesley Stahl returned to emcee the awards dinner, which honored Neri Oxman & William Ackman and 2018 Nobel laureate Jim Allison. Thanks to the event chairs and donors, the event raised more than $10 million. After receiving the Double Helix Medal, Oxman and Ackman announced an extraordinary gift, further breaking the event’s fundraising record to support scientific research and education at CSHL.

William Ackman & Neri Oxman

Neri Oxman & William Ackman are co-trustees of the Pershing Square Foundation. The organization empowers scientists to take on important social causes, including the environment, cancer, and cognitive health. Ackman is also the CEO of Pershing Square Capital Management and chairman of the Howard Hughes Corporation. Oxman is an innovative designer whose fusions of technology and biology have been featured in museums around the world. Her work has yielded over 150 scientific publications and inventions.

“Something we continue to this day is backing young, talented entrepreneurs who are on a mission to solve an important societal problem,” Ackman says. “We believe in taking risks with incredible scientists who have the ability to tackle these complex problems,” Oxman adds.

Dr. Jim Allison

Dr. Jim Allison is regental professor and chair of the MD Anderson Cancer Center’s Department of Immunology. He won the 2018 Nobel Prize in Physiology or Medicine for pioneering the field of cancer immunotherapy. Since then, his research has led to the development of ipilimumab, an FDA-approved therapy for metastatic melanoma, renal cell carcinoma, and lung cancer.

“The perception of immunology has shifted,” Dr. Allison says. “People used to say, ‘Will immunotherapy ever work?’ We now know it works. Immunotherapy is going to be a part of all cancer therapies for almost every kind of cancer.”

The 2023 DHMD was chaired by Ms. Jamie Nicholls and Mr. O. Francis Biondi, Ms. Barbara Amonson and Dr. Vincent Della Pietra, Drs. Pamela Hurst-Della Pietra and Stephen Della Pietra, Mr. and Mrs. John M. Desmarais, Mr. and Mrs. Jonathan Gray, Mr. and Mrs. Jeffrey E. Kelter, Dr. and Mrs. Tomislav Kundic, Mr. and Mrs. Robert D. Lindsay, Ms. Ivana Stolnik-Lourie and Dr. Robert Lourie, Dr. Marcia Kramer Mayer, Dr. and Mrs. Howard L. Morgan, Drs. Marilyn and James Simons, and Mr. and Mrs. Paul J. Taubman.

Since the inaugural gala in 2006 honoring Muhammed Ali, the DHMD has raised over $60 million to support CSHL’s biological research and education programs.

Author Nick Wurm is a Communications Specialist at Cold Spring Harbor Laboratory.

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Ann Emrick. Photo courtesy of BNL

Ann Emrick of East Patchogue has been named Deputy Director for Operations at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory, effective Oct. 1. Emrick, a longtime Brookhaven Lab employee, takes over from Jack Anderson, who stepped down at the end of September after 10 years in the position.

In her new role, Emrick will oversee organizations that provide the bulk of support services for the Lab, including operation and maintenance of more than 300 buildings, several of which are unique, world-class scientific facilities. She will also work closely with Lab Director JoAnne Hewett, Deputy Director for Science & Technology John Hill, and the rest of the Lab’s senior leadership team on day-to-day operations and strategic planning for the Lab’s future.

“I’m excited to have Ann join Brookhaven’s leadership team,” said Laboratory Director JoAnne Hewett. “She brings tremendous experience and knowledge of the Lab, combined with enthusiasm for the role.”

During Emrick’s 36 years at Brookhaven Lab, she has served in progressively more impactful leadership roles across Brookhaven, the Battelle-affiliated labs, and the DOE complex. Most recently, Emrick was the directorate chief operating officer (DCOO) for the Lab’s Environment, Biology, Nuclear Science & Nonproliferation Directorate, the Computational Science Initiative, and the Advanced Technology Research Office.

“I am honored to have been selected for this position and thrilled to be working alongside JoAnne Hewett, John Hill, and the rest of the Lab leadership team at this exciting time at Brookhaven,” said Emrick. “The Lab’s future is bright with the Electron-Ion Collider project underway and our many scientific programs achieving impressive results. I plan to do my best to ensure operational excellence and to make Brookhaven Lab the best place for doing science.”

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From left, Daisy Zavala, Stacey Scott and Krishna Veeramah Photo by John Griffin/Stony Brook University

By Daniel Dunaief

They can’t tell you whether the leading current presidential Republican and Democratic candidates demonstrate signs of cognitive decline or, for that matter whether any real or perceived cognitive decline is greater for one than the other.

Researchers at Stony Brook University, however, have conducted recent studies that may act as a platform to generate a measure of cognitive age that differs from chronological age.

Associate Professors Krishna Veeramah and Stacey Scott and graduate student Daisy Zavala recently published research in the Journal of Gerontology: Biological Sciences in which they studied a combination of cognitive testing done over different time periods and blood tests.

Indeed, the combination of looking at signs of epigenetic changes, or alterations in the environment that affect the way genes work, and studying the effectiveness and variability of tests of memory has the potential to offer some clues about how chronological age may differ from cognitive age. At this point, the scientists have been exploring that relationship, while future work may address not just what is happening, but also why.

Among the data from 142 subjects who took a host of learning tests from 2012 to 2016 during different time periods in the day, increasing epigenetic age was linked with poorer average processing speed and working memory, as well as with greater variability in test performance.

While the statistical analysis accounted for the fact that increasing chronological age had an effect, biological age had an even bigger impact, Veeramah, who is in the Department of Ecology and Evolution and a population geneticist at Stony Brook University, explained.

The study, which Veeramah described as an “early/pilot study,” and will require further follow up, offers another perspective on the different impacts the aging process can have on cognitive function.

The results matched the scientists’ prediction, which was that people who had greater epigenetic age acceleration processed information more slowly and had poorer memory performance on average across the study.

These individuals were not only performing more poorly on average, but were also more variable in their performance.

“This should give us pause about making judgments about people related to their age and what that means about their abilities,” said Scott, who is in the Psychology department.

This study suggests that “how old you are doesn’t tell you so much about how well you’re doing in your cognitive function,” said Scott. Theoretically, the extent to which a person’s body is older than a chronological age could be an indication of what might accelerate or decelerate cognitive function, although longitudinal studies will test this.

The researchers believe this study will contribute to a body of work that is trying to see if researchers can reliably identify biological age acceleration and, if so, how to slow it down.

Testing design

The researchers gathered data from participants who took tests on smartphones provided to them. These phones didn’t receive calls or messages and didn’t have access to the web.

Participants took tests during different times in the day. About 60 percent of study participants were African American and 20 percent were Hispanic/Latino. They also varied in household income, with most participants earning between $20,000 to $60,000.

In one test, people saw symbols at the top of the screen that they had to match with symbols at the bottom as quickly as possible. In another test, people viewed three red dots on a grid for a few seconds. They were distracted by searching for “E’s” and “F’s” on a screen and then had to place the dots back in their original place on the grid.

Participants completed dozens of tests over two weeks, offering a profile of their performance during different times of the day, situations and activities.

By testing people under various conditions, the researchers could get a more comprehensive, complete and realistic understanding of their cognitive state, which also reflects the way people experience a range of competing stimuli.

The scientists were profiling people “in terms of good and bad days” to get an understanding of their “typical performance,” explained Scott.

The SBU scientists suggested that inconsistency was increasingly proposed as a potential early indicator of dementia.

The “unique aspect” of what these scientists did is comparing epigenetic data to ambulatory cognitive measurements, rather than cognitive tests in a lab setting, Veeramah said.

To test the epigenome, Veeramah explored the degree of methylation of DNA from a single blood sample from each participant using a microarray to look at about a million positions in the human genome.

Adding a CH3 group, or methylating, genes tends to make the DNA coil more tightly, making it less likely to interact with other molecules that might turn it on.

Some parts of DNA show changes in methylation that correlate with age, while others are dependent on other things like the environment or specific cell type.

The underlying assumption is that cells pick up more damage and this includes the DNA sequence with time.

Zavala’s dissertation extends this work to look at more long term implications on cognitive health.

Zavala’s research “looks forward,” Scott explained in an email. “Does someone’s epigenetic age acceleration now at the beginning of the study predict their cognitive performance up to three years later?”

Dinner and a hypothesis

Veeramah and Scott, who got married in 2020, decided to combine their expertise for a research project.

“We were talking about our work over dinner and we thought about what I do and the kind of data we have from this existing sample of people” who participated in this cognitive study, said Scott.

The couple wrote a small grant to the research foundation at Stony Brook, which provided seed funding for this study.

Veeramah, whose research covers a broad scope of topics, suggested that the concept of studying these clocks is a fairly new area.

Researchers have been testing whether obesity, Alzheimer’s, and other factors could correlate with the internal environments that cause the kind of wear and tear often associated with aging.

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From left, Joshua Rest and Jackie Collier. The blurred image in the background shows the genome structure of Aurantiochytrium limacinum, including the arrays of rDNAs at the chromosome ends, and the two mirusvirus elements that were discovered. Photo by Donna DiGiovanni

By Daniel Dunaief

They were trying for two years to solve a puzzle that didn’t make sense. Then, a combination of another discovery, some extensive analysis, and a deep dive into the past helped them put the pieces together.

Jackie Collier, Associate Professor at the School of Marine and Atmospheric Sciences at Stony Brook University and Joshua Rest, also an Associate Professor in the Department of Ecology and Evolution at Stony Brook, had been looking closely at the genetic sequence of a marine protist called Aurantiochytrium limacinum. A circular section and pieces at the end of the chromosome seemed inconsistent with the rest of the genes and with the specific type of single-celled organism.

But then, they saw a preprint of a paper in 2022 that the prestigious journal Nature published earlier this year that described a new type of virus, called a mirusvirus, which appeared to have genetic similarities and a signature that matched what they saw in their protist.

Mirus means “strange” or unknown in Latin, which was a way to describe the unusual evolutionary traits of these viruses.

Collier and Rest, working with a group of collaborators, found that a high copy circular structure and genetic elements that integrated at the end of one chromosome resembled this mirusvirus.

“From the perspective of the virus folks, ‘mirus’ was apt because the mirusviruses contain features of the two very distinct ‘realms’ of viral diversity,” Collier explained. “Our results confirm that strangeness, and add more strangeness in terms of two different ways to maintain themselves (circular episomes or integrated into a chromosome) in the same host genome.”

Researchers had discovered the mirusvirus by sequencing DNA they took from the ocean. “What our findings do is connect to a host and hopefully eventually prove that there is a protist that contains a mirusvirus genome,” said Collier.

The Aurantiiochytrium protist, which is part of the Thraustochytrids order, intrigues researchers in part because it produces essential omega-3 fatty acids and carotenoids, which enhances its biotechnology potential. This protist also intrigues Collier because it is involved in decomposing dead mangrove leaves in mangrove forests.

Dormant virus

The Stony Brook scientists have been working on analyzing the genome for a paper they recently published in the journal Current Biology since 2019.

“We had been struggling to figure out what that was,” said Collier. “We had a lot of hints that it had some relationship to some kind of viruses, but it wasn’t similar enough to any known virus. We were struggling to figure out what to call this thing,” which they had tentatively designated CE1, for circular element one.

Identifying viral elements provided the “hook” for the paper.

Rest suggested that the different confounding elements in the protist genome came from two different viruses.

At this point, Collier and Rest think the virus may be something like the herpesvirus, which hides out in human nerve cells. That virus enters a latent phase, remaining quiescent until a host becomes stressed.

John Archibald, Lucie Gallot-Lavallee and others from Dalhousie University in Canada, who are collaborators on this study, are creating the kind of conditions, such as lower food or colder temperatures, that might reactivate the viral DNA, causing it to release viral particles.

The research team has detected similar mirusvirus proteins in other Aurantiochytrium isolates and in four other Thraustochytrid genomes. 

Focusing on this protist

Collier started working on thraustochytrids in 2002, after the first outbreak of QPX disease in Raritan Bay hard clams.

Bassem Allam, who is now the Marinetics Endowed professor in Marine Sciences at SBU asked Collier if she would help understand what was going on with the clams which had QPX disease. That was caused by another Thraustochytrid.

The organism that caused QPX is a relative of the protist that interested Collier.  She chose Aurantiochytrium in part because it was the easiest to grow.

When the Gordon and Betty Moore Foundation started a program to develop molecular genetic methods for diverse marine protists about seven years ago, Collier approached Rest for a potential collaboration.

A key piece, half a century old

In her informatics work, Collier followed a path that Google or artificial intelligence might otherwise have missed.

Like traveling back hand over hand in time through older research, Collier pulled up the references from one study after another. Finally, she found an intriguing study from 1972 that had overlaps with their work.

Scientists had isolated a Thraustochytrid from an estuary in Virginia using the same kinds of methods Collier and Rest used to grow Aurantiochytrium. Using electron microscopy, these earlier researchers characterized its ultrastructure. Along the way, these 1970’s scientists noticed that starved cells released viral particles, which Collier and Rest believe might be the first record of a mirusvirus.

The researchers wrote a short paper that the prestigious journal Science published.

A cat connection

While Collier, who lives in Lake Grove, and Rest, who is a resident of Port Jefferson, are collaborators at Stony Brook, they have also have a feline connection.

In the beginning of the pandemic, a feral cat delivered kittens in Rest’s garage. Rest’s family initially tried to raise them, but allergies made such a pet arrangement untenable. 

A cat lover, Collier was searching for kittens. She adopted two of the kittens, bottle feeding them starting at three days old. When Collier and Rest speak by zoom, Rest’s children Julia, nine, and Jonah, five, visit with the cats virtually.

As for their work, Collier and Rest are intrigued by the possibility of gathering additional pieces to answer questions about this virus.

“For me, the most intriguing question is how common our observations will turn out to be — do many Thraustochytrids have latent mirusviruses?” she explained.

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