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Sechrist model chamber for hyperbaric oxygen therapy. Photo courtesy Renee Novelle

Port Jefferson’s St. Charles Hospital will open its new Center for Hyperbaric Medicine & Wound Healing on July 18, as the hospital seeks to help people with chronic, nonhealing wounds.

The center, which will be located on the second floor of the hospital, will include two hyperbaric chambers that provide 100% pure oxygen under pressurized conditions and will have four examining rooms.

The chamber “provides patients with the opportunity to properly oxygenate their blood, which will increase wound healing and wound-healing time,” said Jason Foeppel, a registered nurse and program director for this new service.

Potential patients will be eligible for this treatment when they have wounds that fail to heal after other treatments for 30 days or more.

Residents with circulatory challenges or who have diabetes can struggle with a wound that not only doesn’t heal, but can cause other health problems as well.

More oxygen in people’s red blood cells promotes wound healing and prevents infection.

The treatment “goes hand in hand to deliver aid to the body’s immune system and to promote a healing environment,” Foeppel said.

Nicholas Dominici, RestorixHealth regional director of Clinical Operations; Ronald Weingartner, chief operating officer, St. Charles Hospital; Jim O’Connor, president, St. Charles Hospital; and Jason Foeppel, program director. Photo courtesy Renee Novelle

St. Charles is partnering with RestorixHealth in this wound healing effort. A national chain, RestorixHealth has created similar wound healing partnerships with other health care facilities in all 50 states.

The new wound healing center at St. Charles is one of several others on Long Island, amid an increased demand for these kinds of services.

Partnering with Healogics, Huntington Hospital opened a hyperbaric chamber and wound healing center in May 2021. Stony Brook Southampton Hospital also has a wound care center.

“There’s a great need for this in our community,” said John Kutzma, program director at the Huntington Hospital center. “We know that there are 7 million Americans living with chronic wounds,” many of whom did not receive necessary medical attention during the worst of the pandemic, as people avoided doctors and hospitals.

Concerns about contracting COVID-19 not only kept people from receiving necessary treatment, but also may have caused nonhealing wounds to deteriorate for people who contracted the virus.

Although Kutzma hasn’t read any scientific studies, he said that, anecdotally, “We’ve had patients that had COVID whose wounds haven’t healed as quickly as non-COVID patients.”

Patients at the Huntington Hospital center range in age from 15 to 100, Kutzma said. People with diabetes constitute about one-third of the patients.

Treatment plan

For the hyperbaric chamber to have the greatest chance of success, patients typically need daily treatments that last between one and a half to two hours, five days a week for four to six weeks. While the time commitment is significant, Foeppel said it has proven effective in wound healing studies.

“We pitch it as an antibiotic treatment,” he said. “You want to complete that full cycle to ensure the body has enough time to complete the healing process.”

Kutzma said Huntington Hospital reviews the treatment plan with new patients.

In following the extensive treatment protocol to its conclusion, he said, “The alternative is to live with this very painful, chronic wound that may lead to amputation.” Given the potential dire alternative, Huntington Hospital doesn’t “have a problem getting that kind of commitment.”

While the treatment has proven effective for many patients, not everyone is medically eligible for the hyperbaric chamber.

Colin Martin, safety director. Photo courtesy Renee Novelle

Some chemotherapy drugs are contraindicators for hyperbaric oxygen treatments. Those patients may have other options, such as skin grafts, extra antibiotics or additional visits with physicians for debridement, which involves removing dead, damaged or infected tissue.

“We invite patients to come in, go through the checklist and see what their plan of attack” includes, Foeppel said.

The cost of the hyperbaric treatment for eligible conditions is generally covered by most health insurance plans, including Medicaid and Medicare, he said. 

The two hyperbaric chambers at St. Charles can treat eight to 10 patients in a day.

Aside from the cost and eligibility, patients who have this treatment frequently ask what they can do during their treatments. The center has a TV that can play movies or people can listen to music.

“We don’t expect you to sit there like in an MRI,” Foeppel said.

As for complaints, patients sometimes say they have pressure in their ears, the way they would if they ascend or descend in an airplane. The center urges people to hold their nose and blow or to do other things to relieve that pressure.

Foeppel encourages patients to use the restroom before the treatment, which is more effective when people don’t interrupt their time in the chamber.

Prospective patients don’t need a referral and can call the St. Charles center at 631-465-2950 to schedule an appointment.

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Markus Seeliger, third from left, with members of his lab, from left, Terrence Jiang. Aziz Rangwala, Ian Outhwaite, Victoria Mingione,YiTing Paung, and Hannah Philipose. Photo from Markus Seeliger

By Daniel Dunaief

When a dart hits the center of a target, the contestant often gets excited and adds points to a score. But what if that well-placed dart slipped off the board before someone could count the points, rendering such an accurate throw ineffective?

With some cases of cancer treatments, that’s what may be happening, particularly when a disease develops a mutation that causes a relapse. Indeed, people who have chronic myeloid leukemia typically receive a treatment called Imatinib, or Gleevac.

The drug works, hitting a target called a kinase, which this white blood cell cancer needs to cause its cells to continue to divide uncontrollably. Patients, however, develop a mutation called N368S, which reduces the effectiveness of the drug.

While mutations typically make it more difficult for a drug to bind to its target, that’s not what’s happening with this specific mutation. Like the dart hitting the center of a board, the drug continues to reach its target.

Instead, in a model of drug resistance several scientists have developed, the mutation causes the drug to decouple.

Pratyush Tiwary with this year’s US top 20 students who are going to the international chemistry olympiad. Photo from Toward

A team of experimental and computational researchers including Markus Seeliger, Associate Professor of Pharmacological Sciences at Stony Brook University, and Pratyush Tiwary, Associate Professor in the Department of Chemistry & Biochemistry at the University of Maryland, published two research papers explaining a process that may also affect the way mutations enable resistance to other drugs.

Seeliger described how different disease-associated mutations bind to Gleevac in a paper published in the Proceedings of the National Academy of Sciences. 

Working with scientists at Memorial Sloan Kettering Cancer Center and Goethe University in Frankfurt, Germany, Seeliger used nuclear magnetic resonance spectroscopy, or NMR. The researchers showed how the drug bound to its target and then released.

Understanding the way diseases like cancer develop such resistance could affect drug discovery, giving pharmaceutical companies another way to prepare for changes diseases make that reduce the effectiveness of treatments.

A ‘hot paper’

Tiwary published research in which Seeliger was a coauthor in late April in the journal Angewandte Chemie that the publication labeled a “hot paper” for its implications in the field. Tiwary developed a way to simulate the kinetic processes that enable the mutated kinases to release the drug.

Tiwary created an artificial intelligence model that extended the time he analyzed the drug-protein interaction from milliseconds all the way out to thousands of seconds.

“Even within the simulation world, if you can quantitatively predict a binding affinity, that’s amazing,” Seeliger said. “It’s extremely hard to calculate kinetics, and he got that right.”

Tiwary, who started talking with Seeliger about five years ago and has been actively collaborating for about three years, uses experimental data to inform the dynamics that affect his simulations.

Seeliger “had done the experiments of the dissociation rates beforehand, but did not have a way to explain why they were what they were,” Tiwary explained in an email. “Our simulations gave him insights into why this was the case and … insight into how to think about drugs that might dissociate further.”

Drug discovery

Tiwary hopes the work enables researchers to look at structural and kinetic intermediates in reactions, which could provide clues about drug design and delivery. While he worked with a single mutation, he said he could conduct such an analysis on alterations that affect drug interactions in other diseases.

He wrote that the computations, while expensive, were not prohibitive. He used the equivalent of 16 independent 64 CPUs for one to two weeks. He suggested that computing advances could cut this down by a factor of 10, which would enable the exploration of different mutations.

“The methods are now so easy to automate that we could run many, many simulations in parallel,” Tiwary explained. Machine learning makes the automation possible.

Given what he’s learned, Tiwary hopes to contribute to future drug begin that addresses mutation or resistance to treatment in other cancers. He also plans to continue to work with Seeliger to address other questions.

Next steps

Seeliger said he plans to extend this work beyond the realm of this specific type of cancer.

He will explore “how common these kinetic mutations are in other systems, other diseases and other kinases,” Seeliger said.

He would also like to understand whether other proteins in the cell help with the release of drugs or, alternatively, prevent the release of drugs from their target. The cell could have “other accessory proteins that help kick out the drug from the receptor,” Seeliger said.

The concept of drug resistance time comes from infectious disease, where microbes develop numerous mutations.

Seeliger, who is originally from Hanover, Germany, said he enjoys seeing details in any scene, even outside work, that others might not notice. 

He described how he was driving with postdoctoral fellows in Colorado when he spotted a moose. While the group stopped to take a picture, he noticed that the moose had an ear tag, which is something others didn’t immediately notice.

As for the research collaboration, Seeliger is pleased with the findings and the potential of the ongoing collaboration between experimental and computational biologists.

“The computational paper, aside from using interesting new methodology, describes why things are happening the way they are on a molecular level,” he said.

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Study authors Liwei Yang, left, and Jun Wang, in the Wang laboratory by the microscope that incorporates the single-cell cyclic multiplex in situ tagging (CycMIST) technology to analyze proteins on single cells. Photo provided by Jun Wang

A new biomedical research tool that enables scientists to measure hundreds of functional proteins in a single cell could offer new insights into cell machinery. Led by Jun Wang, Associate Professor of Biomedical Engineering at Stony Brook University, this microchip assay — called the single-cell cyclic multiplex in situ tagging (CycMIST) technology – may help to advance fields such as molecular diagnostics and drug discovery. Details about the cyclic microchip assay method are published in  Nature Communications.

While newer technologies of single-cell omics (ie, genomics, transcriptomics, etc.) are revolutionizing the study of complex biological and cellular systems and scientists can analyze genome-wide sequences of individual cells, these technologies do not apply to proteins because they are not amplifiable like DNAs. Thus, protein analysis in single cells has not reached large-scale experimentation. Because proteins represent cell functions and biomarkers for cell types and disease diagnosis, further analysis on a single-cell basis is needed.

“The CycMIST assay enables comprehensive evaluation of cellular functions and physiological status by examining 100 times more protein types than conventional immunofluorescence staining, which is a distinctive feature not achievable by any other similar technology,” explains Liwei Yang, lead author of the study and a postdoctoral scholar within the Wang research team and Multiplex Biotechnology Laboratory.

Wang, who is affiliated with the Renaissance School of Medicine and Stony Brook Cancer Center, and colleagues demonstrated CycMIST by detecting 182 proteins that include surface markers, neuron function proteins, neurodegeneration markers, signaling pathway proteins and transcription factors. They used a model of Alzheimer’s Disease (AD) in mice to validate the technology and method.

By analyzing the 182 proteins with CycMIST, they were able to perform a functional protein analysis that revealed the deep heterogeneity of brain cells, distinguished AD markers, and identified AD pathogenesis mechanisms.

With this detailed way to unravel proteins in the AD model, the team suggests that such functional protein analysis could be promising for new drug targets for AD, for which there is not yet an effective treatment. And they provide a landscape of potential drug targets at the cellular level from the CycMIST protein analysis.

The authors believe that CycMIST could also have enormous potential for commercialization.

They say that before this study model with CycMIST, researchers could only measure and know a tip of protein types in a cell. But this new approach enables scientists to identify and know the actions of each aspect of a cell, and therefore they can potentially identify if a cell is in a disease status or not – the first step in a possible way to diagnose disease by analyzing a single protein cell. And compared with standard approaches like flow cytometry, their approach with CycMIST can analyze 10 times the amount of proteins and on a single-cell level.

The researchers also suggest that the cyclic microchip assay is portable, inexpensive, and could be adapted to any existing fluorescence microscope, which are additional reasons for its marketability if it proves to be effective with subsequent experimentation.

Much of the research for this study was supported by the National Institutes of Health’s National Institute of Aging (grant # R21AG072076), other NIH grants, and a Memorial Sloan Kettering Cancer Center Support Grant.

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A view of Shinnecock Bay. Photo by Christopher Paparo/Fish Guy Photos
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A view of Shinnecock Bay. Photo by Christopher Paparo/Fish Guy Photos
Maria Grima holding an invasive European green crab from Shinnecock Bay. Photo by Leeanne Dion
A squid from Shinnecock Bay. Photo by Sara Cernadas-Martin
Konstantine Rounto
Konstantine Rountos with students.
Konstantine Rountos with St. Joseph's University students before going out on a trawl. Photo from Rountos
Brown tide before the restoration on Shinnecock Bay started in 2012. Photo from Chris Gobler
Clearnose skate from Shinnecock Bay. Photo by Sara Cernadas-Martin
Maria Grima. Photo by Sara Cernadas-Martin
Ellen Pikitch with sea horses from Shinnecock Bay. Photo from SBU
A summer flounder. Photo by Christopher Paparo/Fish Guy Photos

By Daniel Dunaief

The Galapagos Islands, the Great Barrier Reef, Little Cayman and … Shinnecock Bay? Yes, that’s correct, the 40 square kilometer bay located on the southern end of Long Island recently joined a distinguished list of celebrated marine locations identified by Mission Blue, a non-profit international organization led by famed marine biologist Sylvia Earle.

Mission Blue named Shinnecock Bay a Hope Spot, one of 132 such locations in the world that it considers critical to the health of the ocean.

Shinnecock Bay has the distinction of being the only Hope Spot in New York State, the only one near a major city and one of three on the Eastern Seaboard.

“The idea that you could have a Hope Spot so close to a major metropolitan area is pretty significant,” said Ellen Pikitch, Endowed Professor of Ocean Conservation Science at Stony Brook University and the School of Marine and Atmospheric Sciences and Director of the Institute for Ocean Conservation Science.

The designation by Mission Blue not only puts Shinnecock Bay in elite environmental company, but it also completes a comeback story driven by scientists, their students, numerous volunteers, and other supportive groups.

“The point of Mission Blue designating this place a Hope Spot isn’t only to bring more people and attention to Shinnecock Bay,” said Pikitch, but is also to “send the message of hope that we can turn things around.”

Pikitch, Christopher Gobler, Endowed Chair of Coastal Ecology and Conservation at the School of Marine and Atmospheric Sciences, and Bradley Peterson, Associate Professor at Somas, led the efforts at the bay.

The scientists created clam sanctuaries in the Western Shinnecock Bay with strict no take rules for people, which helped jump start the restoration. The clams helped meet natural filtration goals.

The researchers also helped restore eelgrass, also called seagrass, which is a more effective natural way to sequester carbon per square inch than the rainforest.

Between 1930 and the start of the project in 2012, New York State had lost about 90 percent of its eelgrass. A task force projected that eelgrass would be extinct in the Empire State by 2030. The bay now has about 100 more acres of eelgrass than it had in 2012.

These efforts have created a “huge leap in the number of forage fish” including bay anchovies and menhaden, said Pikitch, who studies forage fish. “The bay is in a much healthier place now that it was when we started,” she added.

Tough beginnings

Indeed, in 2012, parts or all of the bay had to close because of brown or red tides. The tides sometimes “looked like coffee spilled across the entire bay,” Pikitch said.

The steps the researchers took to improve water quality took some time. “Harmful algal blooms didn’t disappear right away,” Pikitch said. “As the study progressed, the amount of time brown tides occurred got shorter and shorter. Ultimately we stopped seeing brown tides several years ago.”

Red tides, which can cause paralytic shellfish poisoning that could be fatal to people, had also been a problem in Shinnecock Bay. Nearly half the bay was closed to shellfishing in 2011, 2014, and 2015. In 2017 and 2028, about 1/4 of the bay was closed due to red tides. Since 2019, however, red tides haven’t threatened the bay.

On the water

Throughout the restoration process, scientists in training and volunteers contributed to various efforts. Konstantine Rountos, Associate Professor of Biology at St. Joseph’s University in New York, earned his Master’s and PhD and conducted his post doctoral research at Stony Brook University. He also served as the lead research scientist for the Shinnecock Bay Restoration Program trawl survey from 2012 to 2016. 

Rountos called the designation “remarkable and extremely exciting.” When he started working on the bay in 2005 as a Master’s candidate, he saw stressors such as eelgrass declines.

“Not only was the ecosystem showing signs of collapse (decreased seagrass, decreased hard clams, increased harmful algal blooms), but the Bay was supporting fewer and fewer baymen,” he said. The Long Island “cultural identity of ‘living off the bay’ was in serious danger.”

Rountos believes people often overlook the significant ecological importance of this area, driving past these environmental and ecological treasures without appreciating their importance. 

Amid his many Bay memories, he recalls catching a seven-foot long roughtail stingray. “It was very surprising to pull that up by hand in our trawl net,” he said.

A veteran of the bay since 2016, Maria Grima spent time on Shinnecok as an undergraduate at Stony Brook and more recently for her Master’s training, which she hopes to complete this August.

Grima has been studying the invasive European green crab that shreds eelgrass and consumes shellfish such as clams, oysters and mussels. In a preliminary analysis, the population of this crab has declined. Grima noted that it’s difficult to prove cause and effect for the reduction in the number of these crabs.

Rather than pursue a potential career in medicine, which was her initial focus when she arrived at Stony Brook, Grima decided to focus on “fixing the environmental issues that cause human health problems.”

She is “really proud that Shinnecock Bay” achieved the Hope Spot designation. 

One of her favorite Bay memories involves seeing an ocean sunfish, which is a distinctive and large fish that propels itself through water with its dorsal and ventral fins and is the world’s largest bony fish. Seeing the biodiversity on a bay that has had historically poor water quality “gives you hope when you’re on the boat,” Grima said.

When friends and volunteers have joined her on the Bay, she has delighted in watching them interact with seahorses, which “wrap their little tail around your finger.”

Looking toward the future

While Pikitch is pleased with the designation, she said the work of maintaining it continues.

“We can’t rest on our laurels,” she said. “Continued construction on Long Island’s East End and the growing threat of climate change may require additional restoration work. We need to keep a close eye on what is happening in Shinnecock Bay and be ready to take action if necessary.”

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Port Jefferson EMS. Photos by Raymond Janis, captions courtesy Lisa Rodriguez
Princesses with Powertools: Learn to Hand Drill with Reinvented Inc.
Marine Ecosystem Monitoring and Environmental Restoration Research by the Gobler Lab at Stony Brook University
LumenPnP - Open Source Desktop Pick and Place Machine. Company: Opulo
HugMatch
Hamptons Yarn, photo shows Amanda Schaefer.
Engineering Art by Sejal Mehra with family member
Long Island Ghostbusters. Pictured: Cosplayer Dimitrios Haritos,Long Island Ghostbuster
RoboJango (robot) with Maker James Nason of LB Robotics
Representatives of the Dickens Festival
Padawan Lightsaber Training, with the Star Wars- Saber Guild- Endor Temple
Tesla Science Center at Wardenclyffe
Representatives of the Dickens Festival
Smithtown Robotics Team
William Floyd FRC Robotics Team

After a two-year hiatus due to the pandemic, Maker Faire Long Island returned to Port Jefferson village on Saturday, June 11, at the Village Center.

Maker Faire LI is an annual festival held by the Long Island Explorium, a science and engineering museum based in Port Jeff. Its purpose is to promote STEM (science, technology, engineering and mathematics) education by way of innovations and crafts of people throughout the region and country. 

Angeline Judex, executive director of the Explorium, discussed the surprising success of the event after its two-year pause. “We’re really happy with this event,” she said. “It has turned out really well — much better than we actually expected.”

Proceeds from the event will support the Explorium’s various educational programs. The goal of these programs is to enliven STEM through activities that are engaging and fun. Judex said the Explorium hopes to inspire young people and nourish a lifelong pursuit of STEM. 

“It’s really important for children to be inspired and excited about STEM at an early age,” Judex said, adding, “We focus on enriching and inspiring children from K-6 so that they get excited about STEM because this is the future.” She added, “We want to support the next generation of leaders and scientists who are going to be inspired to solve some of the challenges in the environments we live in.”

Hundreds of makers gathered at Harborfront Park to showcase their own unique contributions to the field. Sejal Mehra, one of the presenters at the festival, displayed what she has coined “engineering art.” Her works integrate aspects of collage, engineering and sustainability studies under a common discipline.

“I create ‘engineering art,’ which is made from recycling old computer and electronic parts or plastic that would have otherwise ended up in the trash to show the beauty of STEM,” she said. “I’m on a mission to change the face of STEM through art.”

Makers such as Mehra offer the necessary guidance for young people to pursue STEM. Through their example of creativity and ingenuity, young people are challenged to change the world themselves.  

“I think it’s really important to have programs like this one to help inspire young minds into a lifelong pursuit of STEM because you never know when or how something is going to spark their love for STEM,” Mehra said. “It is also great for young minds to be inspired by young adults like myself because we were just in their shoes and can help motivate them to pursue STEM. Without programs like this, the amount of exposure to the field and its vast possibilities and intersections would not be possible.”

Mehra’s artwork is currently for sale and can be purchased through her website or by contacting her via email or Instagram.

Joining Judex was a group of public officials who offered their support for the museum in its mission to educate the next generation of scientists and engineers. New York State Assemblyman Steve Englebright (D-Setauket), a geologist by profession, spoke of the importance of Maker Faire in encouraging young minds to tackle the impending challenges of environmental degradation.

“The purpose of bringing us all together is to enhance this community, to imagine possibilities for all of the people who live here and visit here, and to use our imagination just a little bit,” he said. “One of the things that’s very important is the narrative and theme that are interwoven around protecting the environment. We’re situated here in beautiful Port Jefferson on the edge of the harbor, and it is a beautiful place to remember the importance of sustainability.”

Suffolk County Legislator Kara Hahn (D-Setauket) was also present for the event. She thanked the Explorium for providing these services and enriching the community.

“I am pleased to be here to support Maker Faire Long Island once again, to support the Explorium, and encourage children and our residents to explore, to innovate, to use their imagination and encourage ingenuity,” she said. “Thank you for all you do to encourage that in children right here in our own backyard.”

Brookhaven Town Councilmember Jonathan Kornreich (D-Stony Brook) recognized Judex for the work she put into making this annual tradition successful once again and for championing STEM and motivating young people.

“I want to thank you not only for the work you did to bring this event together, but for the work you do all year long to create a fun place for kids to do science, to teach kids, to make it accessible to everybody, to bring science to places where maybe it isn’t, and to find new places to suddenly discover science,” the councilmember said.

Kathianne Snaden, Village of Port Jefferson deputy mayor, thanked the many entities that helped make this event possible once again.

“To all of the volunteers, to all of the makers, to the attendees, to our code department, our parks department and our highway department, without all of you coming together to make an event like this happen, we just couldn’t do it,” she said. “To the Explorium for providing cutting-edge technology, programming and hands-on learning for our children, it is just unmatched in this area.”

Village trustee Rebecca Kassay and her husband volunteered as traffic guards during the event. She called it “a pleasure directing parking.”

“As my husband and I stand and direct parking, we look at the children leaving this event and I asked them, ‘What have you made today?’” the trustee said. “Their faces light up and they show me something they’ve made, whether it’s a magnet, whether it’s a whirligig, whether it’s lip balm.” She continued, “It is so important to empower these young people with the gift of demystifying what is in the world around them.”

Englebright concluded the remarks with an anecdote. When the assemblyman was just 14 years old, his science teacher at the time recommended he attend a junior curator program at the Brooklyn Children’s Museum. His decision to heed that advice would reshape the course of his life.

“I became a junior curator and it changed my life,” he said. “The Explorium, this children’s museum, I believe is going to change an awful lot of young people’s lives. Now here I am — with white hair — some years later, and I can tell you of the importance of your programs and the worthiness of everything that you do.”

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In left photo, Zhiyang Zhai, on the right, with John Shanklin and Jantana Keereetaweep; in right photo, Zhiyang Zhai with Hui Liu. Photos courtesy of BNL

By Daniel Dunaief

In a highly competitive national award process, the Department of Energy provides $2.5 million to promising researchers through Early Career Research Funding.

Recently, the DOE announced that Zhiyang Zhai, an associate biologist at Brookhaven National Laboratory, was one of 83 scientists from around the country to receive this funding.

“Supporting talented researchers early in their career is key to fostering scientific creativity and ingenuity within the national research community,” DOE Office of Science Director Asmeret Asefaw Berhe, said in a statement.

Zhai, who has worked at BNL for 11 years, is studying a signaling protein called Target Of Rapamycin (TOR) kinase, which is important in the plant and animal kingdom.

He hopes to develop a basic understanding of the way this kinase reacts to different conditions, such as the presence of carbon, to trigger reactions in a plant, including producing oils through photosynthesis or making seeds.

Zhiyang Zhai. Photo from BNL

“Ancient systems like this evolve in different lineages (like plants and animals) to work differently and [Zhai] wants to find out the details of how it works in plants,” John Shanklin, chair of BNL’s Biology Department, explained in an email. 

Zhai is trying to define which upstream signals interact with TOR and what the effects of those interactions are on TOR to learn how the kinase works.

He is hoping to get a clear idea of how different nodes interact and how signaling through carbon, nutrients and sunlight affects TOR kinase levels and its configuration.

Researchers may eventually use the knowledge of upstream regulators to reprogram responses by introducing enzymes that would cause the synthesis, or degradation, of upstream regulatory metabolites, Shanklin suggested.

This could be a way to “tune” the sensor kinase activity to increase the synthesis of storage compounds like oil and starch.

In the bigger picture, this type of research could have implications and applications in basic science that could enhance the production of renewable resources that are part of a net-zero carbon fuel strategy.

The DOE sponsors “basic science programs to discover how plants and other organisms convert and store carbon that will enable a transition towards a net zero carbon economy to reduce the use of fossil fuels,” Shanklin said.

In applying for the award, Zhai paid “tremendous attention” to what the DOE’s mission is in this area, Shanklin said. Zhai picked out a project that, if successful, will directly contribute to some of the goals of the DOE.

Through an understanding of the way TOR kinase works, Zhai hopes to provide more details about metabolism.

Structure and function

Jen Sheen, Professor in the Department of Genetics at the Harvard Medical School, conducted pioneering work on how TOR kinase regulates cell growth in plants in 2013. Since then, TOR has attracted attention from an increasing number of biologists and has become “a hot and rapidly-developing research direction in plant biology,” Zhai explained.

He hopes to study the structure of TOR using BNL’s Laboratory of Biomolecular Structure at the National Synchrotron Lightsource II.

Zhai, who hopes to purify the plant version of TOR, plans to study how upstream signaling molecules interact with and modify the structure of the enzyme.

He will also use the cryo-electron microscope to get a structure. He is looking at molecular changes in TOR in the presence or absence of molecules or compounds that biochemically bind to it.

Through this funded research, Zhai hopes to explain how signals such as carbon supply, nutrients and sunlight regulates cell growth.

Once he’s conducted his studies on TOR, Zhai plans to make mutants of TOR and test them experimentally to see if a new version, which Zhai described as “TOR 2.0,” has the anticipated effects.

Zhai is building on his experience with another regulatory kinase, called SnRK1, which is involved in energy signaling.

“His expertise in defining SnRK1’s mechanism ideally positions him to perform this work,” Shanklin said.

At this point, Zhai is focused on basic science. Other researchers will apply what he learns to the development of plants for commercial use.

A seminal moment and a call home

Zhai described the award as “very significant” for him. He plans to continue with his passionate research to explore the unknown.

He will use the funds to hire new postdoctoral researchers to build up his research team. He also hopes this award gives him increased visibility and an opportunity to add collaborators at BNL and elsewhere.

The funding will support part of Zhai’s salary as well as that of his staff. He will also purchase some new lab instruments and tap into the award to attend conferences and publish papers.

When he learned he had won the award, Zhai called his mother Ruiming, who lives in his native China. “She is so proud of me and immediately spread the good news to my other relatives in China,” Zhai recalled.

When Shanklin spoke with Zhai after the two had learned of the award, he said he had “never seen Zhai look happier.”Shanklin suggested that this is a “seminal moment” in a career that he expects will have other such milestones in the future.

A resident of Mt. Sinai, Zhai lives with his wife Hui Liu, who is a Research Associate in Shanklin’s group specializing in plant transformation, fatty acids and lipidomics analysis.The couple has two sons, nine-year-old Terence and three-year-old Steven.

As for his work, Zhai hopes it has broader implications.

“The knowledge of TOR signaling will provide us [with] tools to achieve hyperaccumulation of lipids in plant vegetative tissues, which is a promising source for renewable energy,” he said.

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This map shows of the status of marine protected areas in the United States. Credit: Sullivan-Stack et al., Frontiers in Marine Science 2022

By Daniel Dunaief

Time is not on our side.

That’s one of the messages, among others, from a recent paper in Frontiers in Marine Conservation that explored Marine Protected Areas around the United States.

In a study involving scientists at universities across the country, the researchers concluded that the current uneven distribution of MPAs do not offer sufficient protection for marine environments.

Left, Ellen Pikitch holds gooseneck barnacles in The Olympic Coast National Marine Sanctuary, an MPA in Washington State.

 

“The mainland of the United States is not well protected” with no region reaching the 10 percent target for 2020, said Ellen Pikitch, Endowed Professor of Ocean Conservation Sciences at the School of Marine and Atmospheric Sciences at Stony Brook University and a co-author on the study. “The mid-Atlantic is one of the worst of the worst in that regard. We’re not well positioned and we have no time to waste.”

Indeed, the United States, through the administration of President Joe Biden (D), has committed to protecting 30 percent of the oceans by 2030. At this point, 26 percent of the oceans are in at least one kind of MPA. That, however, doesn’t reflect the uneven distribution of marine protection, Pikitch and the other authors suggested.

As much as 96 percent of the protection is in the Central Pacific Ocean, Pikitch explained. That compares with 1.9 percent of the mainland United States and 0.3 percent of the mid-Atlantic.

“We are denying the benefits of ocean protection to a huge portion of the U.S. population,” Pikitch said. “This needs to change if we want the full spectrum of marine life in U.S. ocean waters and to obtain the many benefits to human well-being that this would provide.”

The researchers in the study used a new science-based framework called “The MPA Guide,” which Pikitch helped create. This study represents the first application of this guide to the quantity and quality of marine protection around the United States.

The Guide, which was published in September in the journal Science, rates areas as fully, highly, lightly or minimally protected and is designed to bridge the gap between scientific research and government policies.

Jenna Sullivan-Stack, a research associate at Oregon State University and lead author on the paper, credits Pikitch with helping to create the guide.

Pikitch made “key contributions to this work, especially putting it in context relative to international work and also thinking about how it can be useful on a regional scale for the mid-Atlantic,” Sullivan-Stack explained in an email.

“These findings highlight an urgent need to improve the quality, quantity and representativeness of MPA protection across U.S. waters to bring benefits to human and marine communities,” Sullivan-Stack said in a statement.

Pikitch said MPAs enhance resilience to climate change, providing buffers along shorelines. Seagrasses, which Long Island has in its estuaries, are one of the “most powerful carbon sequesters” on the planet, she explained.

Pikitch suggested there was abundant evidence of the benefits of MPAs. This includes having fish that live longer, grow to a larger size and reproduce more. Some published, peer-reviewed papers also indicate the benefit for nearby waterways.

“I have seen the spillover effect in several MPAs I have studied,” Pikitch said.

To be sure, these benefits may not accrue in nearby waters. That depends on factors including if the area where fishing is allowed is downstream of the protected area and on the dispersal properties of the fished organism, among other things, Pikitch explained.

Lauren Wenzel, Director of NOAA’s Marine Protected Areas Center, said the government recognizes that the ocean is changing rapidly due to climate change and that MPAs are affected by warmer and more acidic water, intense storms and other impacts.

“We are now working to ensure that existing and new MPAs can help buffer climate impacts by protecting habitats that store carbon and by providing effective protection to areas important for climate resilience,” Wenzel said.

The researchers made several recommendations in the paper. They urged the creation of more, and more effective, MPAs, urging a reevaluation of areas with weak protection and an active management of these regions to generate desired results.

They also suggested establishment of new, networked MPAS with better representation of biodiversity, regions and habitats. The researchers urged policy makers to track areas that provide conservation benefits, such as military closed regions.

The paper calls for the reinstatement and empowerment of the MPA Federal Advisory Committee, which was canceled in 2019.

While the National Oceanographic and Atmospheric Administration has no plans to reinstate this committee, is it “considering ways to expand the dialogue and seek advice from outside the government on area-based management,” Wenzel said.

The paper also urges the country to revisit and update the National Ocean Policy and National Ocean Policy Committee, which were repealed in 2018 before plans were implemented.

Wenzel said that the United States recently joined the High-Level Panel for a Sustainable Ocean Economy, a multi-national effort to ensure the country commits to developing a national plan within five years to manage the ocean under national jurisdiction sustainably.

In terms of enforcing MPAs, the Office of National Marine Sanctuaries supports enforcement that fosters voluntary compliance through educating sanctuary users and promoting a sense of stewardship toward the living and cultural resources of the sanctuary, Wenzel added.

“The sanctuary system’s goal is to provide a law enforcement presence in order to deter and detect violations,” she said.

The Office of National Marine Sanctuaries works with the U.S. Coast Guard and the Department of the Interior.

In terms of the impact of the paper, Pikitch said she hopes the paper affects policies and ignites change.

“We need to ramp up the amount and quality of protection in U.S. ocean waters, particularly adjacent to the mainland U.S. and the mid-Atlantic region,” she said.

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This visual presentation shows the words and phrases used on Facebook posts from individuals in the study considered either high- or low-risk for excessive drinking. Credit: Rupa Jose and Andrew Schwartz

Alcoholism can be a difficult condition to diagnose, especially in cases where individuals’ drinking habits are not noticed and physical symptoms have not yet manifested. In a new study, published in Alcoholism: Clinical & Experimental Research, co-author H. Andrew Schwartz, PhD, of the Department of Computer Science at Stony Brook University, and colleagues determined that the language people used in Facebook posts can identify those at risk for hazardous drinking habits and alcohol use disorders.

Collaborating with Schwartz working on The Data Science for Unhealthy Drinking Project is Stony Brook University doctoral candidate Matthew Matero, and Rupa Jose, PhD, lead author and Postdoctoral Researcher at the University of Pennsylvania.

Key to the research was the use of Facebook content analyzed with “contextual embeddings,” a new artificial intelligence application that interprets language in context. The contextual embedding model, say Schwartz, Jose and colleagues, had a 75 percent chance of correctly identifying individuals as high- or low-risk drinkers from their Facebook posts. This rate at identifying at risk people for excessive drinking is higher than other more traditional models that identify high-risk drinkers and those vulnerable to alcoholism.

“What people write on social media and online offers a window into psychological mechanisms that are difficult to capture in research or medicine otherwise,” says Schwartz, commenting on the unique aspect of the study.

“Our findings imply that drinking is not only an individually motivated behavior but a contextual one; with social activities and group membership helping set the tone when it comes to encouraging or discouraging drinking,” summarizes Jose.

Investigators used data from more than 3,600 adults recruited online — average age 43, mostly White — who consented to sharing their Facebook data. The participants filled out surveys on demographics, their drinking behaviors, and their own perceived stress  — a risk factor for problematic alcohol use. Researchers then used a diagnostic scale to organize participants — based on their self-reported alcohol use — into high-risk drinkers (27 percent) and low-risk drinkers (73 percent).

The Facebook language and topics associated with high-risk drinking included more frequent references to going out and/or drinking (e.g., “party,” “beer”), more swearing, more informality and slang (“lmao”), and more references to negative emotions (“miss,” “hate,” “lost,” and “hell”). These may reflect factors associated with high-risk drinking, including neighborhood access to bars, and personality traits such as impulsivity.

Low-risk drinking status was associated with religious language (“prayer,” “Jesus”), references to relationships (“family,” “those who”), and future-oriented verbs (“will,” “hope”). These may reflect meaningful support networks that encourage drinking moderation and the presence of future goals, both of which are protective against dangerous drinking.

Overall, the authors conclude that “social media data serves as a readily available, rich, and under-tapped resource to understand important public health problems, including excessive alcohol use…(The) study findings support the use of Facebook language to help identify probable alcohol vulnerable populations in need of follow-up assessments or interventions, and note multiple language markers that describe individuals in high/low alcohol risk groups.”

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Corina Amor ©Len Marks Photography, 2022/CSHL

By Daniel Dunaief

What if scientists could train the immune system to recognize something specific on the outside of unwanted cells?

That’s what new Cold Spring Harbor Laboratory fellow Corina Amor is doing, as she found an antigen on the surface of senescent cells. She hopes to train a patient’s T-cells to search for these cells, much like providing a police dog with the scent of a missing person or escaped convict.

Amor, who joined Cold Spring Harbor Laboratory in January after earning her medical degree in  at Universidad Complutense de Madrid in Spain and her PhD in the lab of CSHL Adjunct Professor Scott Lowe, recently found a surface molecule called uPAR that is upregulated on senescent, or aging, cells.

If senescent cells excessively accumulate, it can lead to tissue decline and disease like lung and liver fibrosis, Lowe, who is the Cancer Biology Chair at Memorial Sloan Kettering Cancer Center, explained in an email. Senescent cells also contribute to tissue decline as people age.

Studies suggest eliminating these senescent cells could provide therapeutic benefit, she added.

Using artificial T-cells, called CAR-T, for Chimeric Antigen Receptor, Amor looks to use specific antigens to find these senescent cells and eliminate them.

“It was sort of a crazy idea, but it worked and, while much more preclinical and clinical work needs to be done, the concept could lead to better treatments for lung and liver fibrosis, and other diseases that increase as we age,” Lowe wrote.

The combination of an inflamed environment and an ineffective immune system can create conditions that favor the growth and development of cancer.

Amor, who currently has one technician and is planning to add a graduate student this summer at her lab at CSHL, is building on her PhD research.

“My doctoral work was the development of the first CAR-T cells that are able to target senescent cells,” she said. “We were the first in the world to do this.”

Amor, who was recently named to the 2022 Forbes 30 under 30 Europe list, describes this approach as a new frontier for treating senescent cells and one in which researchers would need to clear numerous hurdles before developing clinical therapies.

She is searching for other antigens on the surface of cancerous and fibrous cells that would increase the specificity of these synthetic immune cells.

Combining antigens could be the key to avoiding off target effects that might cause the immune system to attack healthy cells.

Amor plans to tap into CSHL’s affiliation with Northwell Health to analyze clinical samples that might provide a better understanding of various potential markers.

Fellowship route

Cold Spring Harbor Laboratory is one of several programs in the country that provides talented researchers with the opportunity to go directly from finishing their PhD to leading their own lab.

Amor is following in the footsteps of her MSKCC mentor Lowe, who also had been an independent fellow at CSHL.

Lowe saw some similarities in their career paths, as they both made “unexpected discoveries during our Ph.D. research that were not only important, but clearly set a path for future research,” he explained in an email.

Lowe describes Amor as an “intense and driven scientist” who has an “extraordinary bandwidth to get things done, and a mental organization that allows her to execute science efficiently.” He believes her work is game changing at many levels and opens up numerous new directions for scientific study.

Lowe is “extraordinarily proud of [Amor] for becoming a CSHL fellow – and I hope she both contributes and benefits from the lab as I did,” he wrote in an email.

Amor said CSHL provided an ideal balance between finding collaborators who worked in similar areas, without competing for the same resources and conducting similar research.

“The last thing you want is to go somewhere and be completely isolated,” she said. “You also don’t want to be at a place where there’s three other people doing the same thing and you’re not adding anything.”

She feels like she had a “nice synergy” with CSHL, which is trying to expand its immunology research. 

As the first person to bring cellular therapy to CSHL, she has already started collaborating with several groups. 

Amor recognizes the challenges ahead in training scientists who often have their own ideas about the questions they’d like to ask.

“The science is the easy part” and it comes naturally, but there is a “learning curve in how to manage people,” she said.

She appreciates the opportunity to talk with senior researchers at Cold Spring Harbor Laboratory and plans to attend courses and seminars for principal investigators who are starting out.

When she was in graduate school, Amor said she rotated through different labs. When everything didn’t work as she might have hoped during those rotations, she said she had the opportunity to learn from those experiences.

“When training people in the lab, I try to be really specific about what I want to do” while also ensuring that the researchers understand and appreciate the bigger picture and context for individual experiments, she said.

Originally from Madrid, Amor felt comfortable during her five years in Manhattan and is enjoying the open space and fresh air of Long Island in her role at CSHL. She also appreciates the chance to kayak in the waters around Long Island.

When she was around seven years old, Amor said her mother Esperanza Vegas was diagnosed with breast cancer. By participating in a clinical trial for a new drug, her mother fought off the disease.

“That made me realize how important science and research is,” Amor said.

During her educational training, Amor went directly from high school into a six-year program in which she earned a bachelor’s degree and a medical degree.

By the time she finished her PhD, she was hooked on research.

She appreciates the advice she received from Lowe, who encouraged her to conduct experiments despite the risks.

“Don’t get paralyzed at the beginning by fear,” she said. “Do the experiment and see what happens.”

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Paul Freimuth and co-author Feiyue Teng, a scientist in Brookhaven Lab’s Center for Functional Nanomaterials (CFN), at the light microscope used to image bacteria in this study. Photo from BNL

By Daniel Dunaief

Researchers regularly say they go wherever the science takes them. Sometimes, however, the results of their work puts them on a different path, addressing new questions.

So it was for Paul Freimuth, a biologist at Brookhaven National Laboratory. Freimuth was studying plant proteins of unknown function that he thought might play a role in the synthesis or modification of plant cell walls. The goal was to produce these proteins in bacteria or yeast to facilitate an understanding of the protein structures.

When he inserted plant genes into bacteria, however, one of those genes experienced a phase shift, producing a misfolded protein that, when produced in high enough quantities, killed the bacteria.

Working with several interns over the course of five years, as well as a few other principal investigators, Freimuth discovered that this protein had the same effect as antibiotics called aminoglycosides, which are the current treatment for some bacterial infections. He recently published the results of these studies in the journal Plos One.

Aminoglycosides enter the cell and cause ribosomes to create proteins in an error-prone mode, which kill the bacterial cells. The way these proteins kill the cells, however, remains a mystery. Antibiotic-treated cells produce numerous proteins, which makes determining the mechanism of action difficult.

The protein Freimuth studied mirrors the effect of treating cells with aminogylcosides. Researchers now have a protein they can study to determine the mechanism of cell killing.

To be sure, Freimuth said the current research is at an early stage, and is a long way from any application. He hopes this model will advance an understanding of how aberrant proteins kill cells. That information can enable the design of small molecule drugs that mimic the protein’s toxic effect. He believes it’s likely that this protein would be toxic if expressed in other bacteria and in higher cells, but he has not tested it yet.

With antibiotic resistance continuing to spread, including for aminoglycosides, Freimuth said the urgency to find novel ways to kill or inhibit bacterial growth selectively without harmful side effects has increased.

Aminoglycosides cause the ribosome to shift coding phases or to make other errors. The model toxic protein he studied resulted from the bacteria starting to translate amino acids at an internal position, which produced a new, and, as it turns out, toxic sequence of amino acids.

The phase-shifted gene contained a stop codon located just 49 codons from the start site, which means that the toxic protein only contained 48 amino acids, which is much shorter than the average of 250 to 300 amino acids in an E. coli protein.

Since the model toxic protein was gene-encoded rather than produced by an antibiotic-induced error in translation, Freimuth’s team were able to study the sequence basis for toxicity. The acutely toxic effect was dependent on an internal region 10 amino acids in length.

Narrowing down the toxic factor to such a small region could help facilitate future studies of the mechanism of action for this protein’s toxic effect.

Misread signal

Freimuth and his team discovered that the bacteria misread the genetic plant sequence the researchers introduced. The bacteria have a quality control mechanism that searches for these gibberish proteins, breaking them down and eliminating them before they waste resources from the bacteria or damage the cell.

When Freimuth raised the number of such misfolded proteins high enough, he and his colleagues overwhelmed the quality control system, which he believes happened because the misfolded protein affected the permeability of the cell membrane, opening up channels to allow ions to flood in and kill the cell.

He said it’s an open question whether the protein jams open existing channels or becomes directly incorporated into the membrane, compromising membrane stability.

He showed that cells become salt-sensitive, indicating that sodium ion concentration increases. At the same time, it is likely that essential metabolites are leaking out, depriving the cell of compounds it needs to survive.

Now that the bacteria has produced this protein, Freimuth can use various tools and techniques at BNL, including the X-ray beamlines for protein crystallography and the cryo electron microscope, which would provide ways to study the interaction of the protein with cell components. High resolution structures such as the ones he hopes to determine could be used to guide drug design.

Freimuth is in the process of applying for National Institutes of Health funding for additional research, which could help the NIH’s efforts to counter the increasing spread of antibiotic resistance.

Freimuth has worked at BNL since 1991. He and his wife Mia Jacob, who recently retired from her role in graphic design in Stony Brook University’s Office of Marketing and Communication, reside in East Setauket.

The couple’s daughter Erika, who lives in Princeton and recently got married, works at Climate Central as an editor and writer. Their son Andrew works in Port Jefferson at an investment firm called FQS Capital Partners.

When Freimuth is not working at the lab, he enjoys sailing, kayaking and canoeing. During the pandemic, he said he purchased a small sailboat, with which he has been dodging the ferry in Port Jefferson Harbor.

Originally from Middletown, Connecticut, Freimuth was interested in science from an early age. He particularly enjoyed a mycology class as an undergraduate at the University of Connecticut.

As for his unexpected research with this protein, the biologist is pleased with the support he received from Brookhaven National Laboratory.

He said BNL enabled him to address the biofuel problem from protein quality control, which is a new angle. “BNL appreciates that valuable ideas sometimes bubble up unexpectedly and the lab has ways to assist investigators in developing promising ideas,” he said.

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