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Benjamin Cowley. Photo courtesy of CSHL Communications

By Daniel Dunaief

Most behaviors involve a combination of cues and reactions. That’s as true for humans awaiting a response to a gesture like buying flowers as it is for a male fruit fly watching for visual cues from a female during courtship. 

The process is often a combination of behaviors and signals, which the visual system often processes as a way of determining the next move in a courtship ritual.

At Cold Spring Harbor Laboratory, Assistant Professor Benjamin Cowley recently published research in the prestigious journal Nature in which he used a so-called deep neural network to mirror the neurons involved in a male fly’s vision as it interacts with a potential female mate.

Working with a deep neural network that reflects the fly’s nerve cells, Cowley created a knockout training process, in which he altered one set of neurons in the model at a time and determined their effect on the model and, with partners who conduct experiments with flies, on the flies themselves.

Cowley’s lab group, which includes from left to right, Rabia Gondur, computational research assistant, Filip Vercuysse, postdoctoral researcher, Benjamin Cowley, and Yaman Thapa, graduate student. Photo by Sue Weil-Kazzaz, CSHl Commnications.

Cowley worked closely with his former colleagues at the Princeton Neuroscience Institute, including Professor Jonathan Pillow and Professor Mala Murthy. His collaborators genetically silenced a fruit fly’s neuron type, observing the changes in behavior. Cowley, meanwhile, trained his deep neural network on this silenced behavior while also “knocking out” model neurons, teaching the model by perturbing it in a similar way to the changes in the fruit fly circuitry.

This approach proved effective, enhancing the ability of these models not only to understand the wiring involved in processing visual information and translating that into behavior, but also to provide potential clues in future experiments about similar cellular dysfunction that could be involved in visual problems for humans.

What researchers can infer about the human visual system is limited because it has hundreds of millions of neurons. The field has taken decades to build artificial visual systems that recognize objects in images. The systems are complex, containing millions of parameters that make them as difficult to explain as the brain itself.

The fly visual system, which is the dominant focus of the fly’s brain, occupying about 70 percent of its 130,000 neurons, provides a model system that could reveal details about how these systems work. By comparison, the human retina has 100 million neurons.

“To build a better artificial visual system, we need to know the underlying mechanisms,” which could start with the fly, Cowley said. “That’s why the fruit fly is so amenable.”

Researchers need to know the step-by-step computations going from an image to neural response and, eventually, behavior. They can use these same computations in the artificial visual system.

‘A suite of tools’

The fly’s visual system is still robust and capable, contributing to a range of behaviors from courtship to aggression to foraging for food and navigating on a surface or through the air as it flies.

The fly “gives us a whole suite of tools we can use to dissect these circuits,” Cowley said.

The fly visual system looks similar to what the human eye has, albeit through fewer neurons and circuits. The fruit fly visual system has strong similarities to the early processing of the human visual system, from the human eye to the thalamus, before it reaches the visual cortex in the occipital lobe.

Interpreting the visual system for the fly will “help us in understanding disorders and diseases in human visual systems,” Cowley said. “Blindness, for the most part, occurs in the retina.”

Blindness may have many causes; a large part of them affect the retina and optic nerve. This could include macular degeneration, cataracts, diabetic retinopathy and glaucoma.

In its own right, understanding the way the visual processing system works in the fly could also prove beneficial in reacting to the threat of invasive species like mosquitoes, which pass along diseases such as malaria to humans.

Visual channels

Anatomists had mapped the fly’s 50 visual channels, called optical glomeruli. In the past decade, researchers have started to record from them. Except in limited cases, such as for escape reflex behaviors, it was unknown what each channel encoded.

Cowley started the research while a postdoctoral researcher at Princeton Neuroscience Institute in Jonathan Pillow’s lab and finished the work while he was starting his own lab at CSHL. Mala Murthy’s lab, who is also at Princeton, performed the silencing experiments on fruit flies, while Cowley modeled the data.

Through hundreds of interactions between the flies in which some part of the fly’s visual system was silenced, Cowley created a model that predicted neuronal response and the behavior of the fly.

The deep neural network model he used deploys a new, flexible algorithm that can learn its rules based on data. This approach can be particularly helpful in situations when researchers have the tools to perturb the system, but they can’t recover or observe every working part.

In some of the experiments, the males became super courters, continuing to engage in courtship activities for 30 minutes, which, given that the fly lives only three weeks, is akin to a date that lasts 25 days.

It is unclear why these flies become super courters. The scientists speculate that silencing a neuron type may keep the male from being distracted by other visual features.

In the experimental part of the experiments, the researchers, including Dr. Adam Calhoun and Nivedita Rangarajan, who both work in Murthy’s lab, tried to control for as many variables as possible, keeping the temperature at 72 degrees throughout the experiment.

“These flies live in nature, they are encountering so much more” than another fly for potential courtship, said Cowley, including the search for food and water.

This research addressed one small part of a behavioral repertoire that reveals details about the way the fly’s visual system works.

A resident of Huntington, Cowley grew up in West Virginia and completed his undergraduate work and PhD at Carnegie Mellon in Pittsburgh.

An avid chess player, which is a field that has included artificial intelligence, Cowley, who spent much of his life in a city, appreciates having a backyard. He has learned to do some landscaping and gardening.

Cowley had been interested in robotics in college, until he listened to some lectures about neuroscience.

As for the next steps in his work, Cowley hopes to add more complex information to his computational system, suppressing combinations of cells to gather a more complete understanding of a complex system in action.

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Lucille Betti-Nash demonstrates the pencil technique at the workshop.

By Daniel Dunaief

Their illustrations, which have graced the pages of journals for decades, tell tales that move and inspire people, emphasizing and recreating the beauty, power, elegance and fine structures of living and long extinct creatures.

Invited by Zooreach to join a workshop that employs a combination of story telling, theater and art, Stony Brook residents Stephen Nash and Lucille Betti-Nash, who are both successful scientific illustrators and have been married since 1990, recently traveled to Coimbatore, Tamil Nadu State in Southern India for two weeks to share their talents with local artists focusing on conservation and climate change.

The Nashes believe India is “poised to become a superpower and yet, one of the greatest challenges it faces is climate change” as well as population control, said Stephen Nash, Scientific Illustrator for the IUCN SSC Primate Specialist Group and Adjunct Professor in the Department of Art at Stony Brook University.

Indeed, during their fortnight in India, the Nashes experienced temperatures that were over 100 degrees every day. At the same time, a lighter monsoon season last year, which runs from June through September, meant that the reservoirs, which provide cities with water, were depleted and local wildlife was struggling to find places to drink.

Stephen and Betti-Nash, who had worked at Stony Brook and is now retired and doing freelance work, had hoped to see elephants during their trip, but the animals had retreated to more remote regions to find water. The Nashes did, however, see plentiful cows wandering. People practicing Hinduism consider cows sacred.

With support from the workshop provided by the US Consulate General, Chennai that is part of the Art for Conservation Program of Zoo Outreach Organization, the Long Island illustrators enjoyed their trip, made meaningful connections with local artists, and appreciated the amenities their hosts provided, including air conditioned rooms.

The Nashes continue to be in contact with the artists and appreciate how their hosts, Payal and Sanjay Molur, who is the Executive Trustee of Zooreach, took care of them “as though we were family.”

First steps

Before they traveled to India, the Nashes, who have done workshops in Peru in 2016 and Brazil in 2017, provided google drives with a set of folders including copyright free books on natural history that revealed various rendering techniques. They also shared United States government slides that revealed how artists depicted statistics of climate change.

Once the three-day class they taught began, the Nashes started their presentation with an introduction to the field of scientific illustration, including medical, forensic, technical, biological, archaeological, and paleontological areas, among others.

They discussed various illustrating techniques, from rendering various forms of wildlife to organizing and presenting scientific data. They communicated the importance of sticking to the scientific facts when producing art related to climate change and conservation.

The class, which was comprised of educators and artists in their 20’s and 30’s, were most intrigued by pen and ink illustrations. Using a pen dipped in ink, each artist could control the darkness and width of any mark by applying different pressure and changing the angle at which the pen crossed a page.

“We were pleasantly surprised by how well they took to pen and ink,” said Nash.

The Nashes didn’t bring any India ink, figuring that they could readily find it in the country that bears its name. “We were thinking it would be widely available, but we could not find it,” said Betti-Nash. “We had to settle for fountain pen ink, which was not waterproof.”

The Nashes and the students in the class discussed Manga, which are Japanese comics and graphic novels as a way of using the power of art as a sequential medium.

Betti-Nash demonstrated one of her technical strengths with water colors.

The students were “enraptured” when Nash created one of his illustrations, “watching every move with colored pencils,” Betti-Nash said.

Nash suggested they were hoping to inspire their students to come up with “their own local way of pictorially rendering data that would be more meaningful for them and for the people in their immediate village or community.”

To create illustrations that address the challenges of climate change and conservation, Nash takes what he described as a “Bing Cosby” approach, in which he tries to “accentuate the positive.” Optimistic by and about nature, Nash has seen how ecosystems can recover if allowed by humans. He prefers to show the beauty of an endangered animal rather than show a landscape denuded of trees with a lonely gibbon siting on a tree stump.

“I wouldn’t want an image with that negativity on my own walls,” Nash said. “It’s better to help people appreciate [nature] than to show the possible” cataclysmic results of climate change.

Betti-Nash urged the artists to draw their favorite animals, recreating whatever was their spark animal that led them to the field of conservation. Some chose endangered sharks, which are a part of the bycatch when commercial fishing vessels hunt for more valuable fish. Local students shared their appreciation for snakes, who perform an important role in Indian ecosystems.

Face to face with the real thing

Nash met the Molurs, who invited them to visit India, in the mid 1980’s, when he had done a drawing for a conservation education campaign on the lion-tailed macaque.

When he arrived in India, Nash saw three species of primates in the hills alongside the road in a protected area, including the lion-tailed macaque. Nash thought the animal was the size of a German shepherd, but realized it was closer to the dimensions of a domestic cat.

Nash focuses on capturing the character as well as the characteristics of an animal and suggested artists needed to be aware of the goals of their illustrations.

Betti-Nash likes to demonstrate the interaction of the animals she’s illustrating with the environment, including what they eat and what they provide to the ecosystem.

As for the workshop, Betti-Nash suggested the purpose was to “draw people in” and to get the artists to learn ways to be creative in their messages about conservation and climate change.

Nash added that they wanted to “open the students’ eyes to the possibilities and the vastness of scientific illustration” and to improve their analytic observational skills.

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Harborfields High School science research students Jessica Dean, Jackson Dunham, Alexa Green, Riley Lyons and Leah Vapnyar complete their last session at the Cold Spring Harbor Labs Science Journal Club. Photo courtesy of Harborfields CSD

Harborfields High School science research students Jessica Dean, Jackson Dunham, Alexa Green, Riley Lyons and Leah Vapnyar recently completed their final session at the Cold Spring Harbor Laboratory’s Science Journal Club. The lab offers this program exclusively to Harborfields students.

During this school year, these five students attended 15 biweekly sessions at the Carnegie Library on the CSHL campus and presented landmark papers with both scientists and archivists. Additionally, they received a behind-the-scenes look at three labs on the cutting edge of research in breast cancer, neuroscience,and plant genetic engineering. Each student was presented with a certificate by the library archivists and scientists they had worked with throughout the year.

“The Science Journal Club gave these students not only an opportunity to enhance their public speaking skills, but also a chance to see real-world applications of the science concepts they learn in class,” science research teacher Michael Pinto said.

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Photo from Vanderbilt Museum

Join scientists from Brookhaven Lab for Science in the Community as they discuss the wonders of the universe at the Suffolk County Vanderbilt Museum and Reichert Planetarium, 180 Little Neck Road, Centerport on Saturday, June 1, from 9:30 a.m. to 2 p.m.

Enjoy hands-on experiences that show the different weights in different planetary gravities, explore craters of the moon, and more!

The Vanderbilt Museum and grounds and Reichert Planetarium will open at 9:30 am and admission will be FREE for all members of the public until 2:00 pm.

Visitors will have access to the grounds as well as exhibits in the Vanderbilt Mansion and Marine Museum.

Seating for the scientific talks and Planetarium shows require reservations. Click on the shows below to reserve your seat. For more information, visit www.vanderbiltmuseum.org.

10:00 am

“Vera Rubin Observatory and LuSEE Night”
Scientist Steven Bellavia of Brookhaven Lab’s Collider-Accelerator Department will share his talk about these recent projects (45 minutes).

Reserve Seat

11:00 am

“A Guide to Galactic Cosmic Rays”
Scientist Jessica Gasparik of Brookhaven Lab’s NASA Space Radiation Laboratory will share a talk about galactic cosmic rays (45 minutes).

Reserve Seat

Noon

“Are We All Made of Star Stuff? How Elements and Stars Work”
Scientist Trevor Olsen of Brookhaven Lab’s NASA Space Radiation Laboratory will share a talk about composition of matter and nucleosynthesis (45 minutes).

Reserve Seat

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An international panel of sleep experts including researchers at Stony Brook University formally agree in a consensus statement that reducing pre-bedtime digital media, especially for children and adolescents, will improve sleep health. Getty Images

SBU Professor Lauren Hale Chairs the National Sleep Foundation’s panel that published a consensus statement

Since the smartphone’s emergence in 2007, digital screen time has ballooned in use over the years for children and adults. How use of smartphones and other digital screen devices affects sleep continues to be debated. In a review of 574 peer-reviewed published studies on the issue, an international panel of sleep experts selected by the National Sleep Foundation (NSF) has drawn up a consensus statement about digital screen use and sleep.

The consensus statement, titled “The Impact of Screen Use on Sleep Health Across the Lifespan: A National Sleep Foundation Consensus Statement,” is published in Sleep Health, the journal of the NSF. They assessed studies on screen time and its effects on sleep including research on children, adolescents, and/or adults.

After an extensive review of this large collection of studies over the course of a year, the panel reached consensus on a number of key points.

They agreed that: 1) In general, screen use impairs sleep health among children and adolescents; 2) The content of screen use before sleep impairs sleep health of children and adolescents, and 3) Behavioral strategies and interventions may attenuate the negative effects of screen use on sleep health.

”Upon review of the current literature, our panel achieved consensus on the importance of reducing pre-bedtime digital media to improve sleep health, especially for children and adolescents,” says Lauren Hale, PhD, Chair of the Consensus Panel and Professor in the Program of Public Health at Stony Brook University, and in the Department of Family, Population, and Preventive Medicine at the Renaissance School of Medicine at Stony Brook. “We also identified the gaps in the literature and the need for future research.”

The NSF provides recommendations for best practices to reduce the impact of screen use on sleep.

In summary, they suggest:

  • Avoiding stimulating or upsetting material near bedtime
  • Implementing early, regular, and relaxing bedtime routines without screens
  • Setting time limits around screen use, especially in the evening and at night
  • Parents talking with children about how using tech and screens can impact sleep
  • Parents modeling appropriate nighttime screen use for children

“The expert panel examined available scientific evidence, paying close attention to studies that examined whether, how, and for whom screen use might negatively impact sleep health. We found that stimulating content of screen use, particularly at night, has a negative effect on sleep health in young people,” adds NSF Vice President of Research and Scientific Affairs, Joseph Dzierzewski, PhD.

Lauren Hale and three other coauthors on the consensus statement were from Stony Brook University:  Gina Marie Mathew, Isaac Rodriguez, and librarian Jessica A. Koos, who helped identify the published peer-reviewed original research and literature reviews using databases, including the National Library of Medicine’s PubMed, Elsevier’s EMBASE, and Clarivate’s Web of Science.

Insufficient sleep duration is both widespread and associated with a higher risk of adverse health outcomes, including obesity, cardiovascular disease, and depression. Having inconsistent sleep schedules is also associated with adverse health outcomes. For more information about sleep health, see this NSF webpage on Sleep Health Topics.

 

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From left, Nilanjan Chakraborty, Associate Professor in Mechanical Engineering at SBU and IV Ramakrishnan, Professor of Computer Science, demonstrate how CART could hold a cup and move its arm. Photo by John Griffin/SBU

By Daniel Dunaief

Caretakers of those with Amyotrophic Lateral Sclerosis (or “Lou Gehrig’s disease”) have an enormous responsibility, particularly as the disease progresses. People in the latter stages of the disease can require around-the-clock care with everything from moving their limbs to providing sustenance.

IV Ramakrishnan, Professor of Computer Science and an Associate Dean in the College of Engineering and Applied Sciences at Stony Brook University, recently received a $1.5 million grant from the U.S. Army to lead a team that is building a Caregiving Robot Assistant, or CART, for ALS patients and their caregivers. 

The grant, which is for three years, will cover the cost of building, testing and refining a robot that a caregiver can help train and that can provide a helping hand in challenging circumstances.

Using off the shelf robot parts, Ramakrishnan envisions CART as a robotic arm on a mobile base, which can move around and, ultimately, help feed someone, get them some water and help them drink or open and close a door. They are also developing a special gripper that would allow the robotic arm to switch a channel on a TV or move a phone closer.

In working through the grant process, Ramakrishnan emphasized the ability of the robot, which can learn and respond through artificial intelligence programs he will create, to take care of a patient and offer help to meet the needs of people and their caregivers who are battling a progressive disease.

“As the needs evolve, the caregiver can show the robot” how to perform new tasks, Ramakrishnan said.

The project includes collaborators in Computer Science, Mechanical Engineering, Nursing, the Renaissance School of Medicine, and clinical and support staff from the Christopher Pendergast ALS Center of Excellence in the Neuroscience Institute at Stony Brook Medicine.

At this point, Ramakrishnan and his team have sent out fliers to recruit patients and caregivers to understand the physical challenges of daily living. 

Ramakrishnan would like to know “what are the kinds of tasks we should be doing,” he said, which will be different in the stages of the disease. They know what kinds of tasks the robot can do within limits. It can’t lift and move a heavy load.

Once the team chooses the tasks the robot can perform, they can try to program and test them in the lab, with the help of therapists and students from the nursing school.

After they develop the hardware and software to accomplish a set of actions, the team will recruit about a dozen patients who will test the robot for one to two weeks. Members of the ALS community interested in the project can reach out to Ramakrishnan by email.

A biostatistician will be a part of that group, monitoring and calculating the success rate.

At this point, the development and testing of the robot represents a pilot study. After the group has proven it can work, they plan to submit a follow up proposal and, eventually, to apply for approval from the Food and Drug Administration.

Ramakrishnan estimates the robot will cost around $30,000, which is about the same cost as a motorized wheelchair. He is unsure whether Medicare will cover this expense.

As a part of the development, Ramakrishnan recognizes that the first goal, similar to the Hippocratic Oath doctors take, is to do no harm. He and his team are incorporating safety features that make the robot withdraw automatically if it gets too close to someone.

A key part of the team

Members of the CART team: Vibha Mullick, and her husband, ALS patient Anuraag Mullick, are in the center. Back row, from left: Clare Whitney, Nilanjan Chakraborty, Theresa Imperato, C.R. Ramakrishnan, and Wei Zhu. Front row, from left, are Maria Milazzo and I.V. Ramakrishnan. Photo by John Griffin

Vibha Mullick, a Senior Web and Database Analyst in Computer Science and resident of South Setauket, will be a key team member on the project.

Mullick has been caring for her husband Anuraag Mullick, who is 64 and was diagnosed with ALS in 2016. Anuraag Mullick is confined to a wheelchair where he can’t swallow or breathe on his own.

“My husband also wants to participate” in the development, said Mullick, who spends considerable time reading his lips.

Caring for her husband is a full-time job. She said she can’t leave him alone for more than five or 10 minutes, as she has to suction out saliva he can’t swallow and that would cause him to choke. When she’s at work, a nurse takes care of him. At night, if she can’t get a nurse, she remains on call.

If her husband, who is in the last stage of ALS, needs to turn at night, use the bathroom or needs anything he makes a clicking sound, which wakes her up so she can tend to his needs.

 “It tires me out,” Mullick said. In addition, she struggles to take care of typical household chores, which means she can’t always do the dishes or wash the laundry. She suggested a robot could help caregivers as well as ALS patients.

In the earlier stages of ALS, people can have issues with falling. Mullick suggests a robot could steady the person so they can walk. She has shared the news about the project with other members of the ALS community.

“They are excited about it and encouraged,” she said. 

Origin of the project

The idea for this effort started with a meeting between Ramakrishnan and the late Brooke Ellison, a well-known and much beloved Associate Professor at Stony Brook University who didn’t allow a paralyzing car accident to keep her from inspiring, educating and advocating for people with disabilities.

Encouraged by SBU Distinguished Professor Miriam Rafailovich, who was a friend of Ellison’s, Ramakrishnan met with Ellison, whose mother Jean spent years working tirelessly by her side when she earned a degree at Harvard and worked at Stony Brook.

Ramakrishnan, who developed assistive computer interactions technologies for people with vision impairments, asked Ellison what a robot arm could do for her and mean for her. 

He recalled Ellison telling him that a robot arm would “transform my life,” by helping feed her, set her hair, or even scratch an itch.

“That moved me a lot,” said Ramakrishnan.

While CART will work with one population of patients, it could become a useful tool for patients and their caregivers in other circumstances, possibly as a nursing assistant or for aging in place.

Road to Stony Brook

Ramakrishnan, who is a resident of East Setauket, was born in Southern Tamil Nadu in India and attended high school in what was then called Bombay and is now Mumbai.

He earned his undergraduate degree from the Indian Institute of Technology and his PhD from the University of Texas at Austin.

Ramakrishnan is married to Pramila Venkateswaran, an award-winning poet and is retiring this summer after 33 years as a Professor of English at Nassau Community College. The couple has two grown children, Aditi Ramakrishnan, who is a physician scientist at the Washington University in St. Louis and Amrita Mitchell-Krishnan, who is a clinical pediatric psychologist.

As for the work on CART, Ramakrishnan is eager to help patients and caregivers. The ultimate goal is to “reduce the caregiving burden,” he said.

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Leaders from Northwell’s Cancer Institute and its Center for Genomic Medicine celebrate the opening of the Molecular Diagnostic Laboratory. From left to right, Joseph Castagnaro, Jeff Boyd, Dwayne Breining, Richard Barakat, Naima Loayza, Anna Razumova, Angelo Carbone, Rita Mercieca and Kathryn Cashin. Photo courtesy of Northwell Health

By Daniel Dunaief

Northwell Health Cancer Institute and its Center for Genomic Medicine opened a Molecular Diagnostics Laboratory, which will reduce the cost of testing and shorten the time to get test results for cancer tests.

At a cost of $3.2 million, the 2,800 square foot facility will use next generation sequencing to provide tumor and patient genomic profiling and to assist in testing for biomarkers and determining the choice of cancer therapy.

The MDL, which is using the space Northwell Health Labs owned, will offer an array of tests in a phased approach. It is starting with a set of single gene tests to inform precision therapies for lung, melanoma, pancreatic, and colorectal cancer, which can be conducted in 24 to 72 hours.

“We like to get cancer therapy started as soon as possible for patients with metastatic disease,” said Jeff Boyd, vice president and chief scientific officer and director of the Northwell Health Cancer Institute’s Center for Genomic Medicine. When Northwell sent out similar tests to for-profit centers, the results, depending on the test, could take weeks.

The MDL is performing these tests on patients with advanced stage disease and/or recurrent diseases, which increases the need to generate results quickly.

“That makes a huge difference for the ordering oncologist and, most especially and importantly to the patient,” said Boyd. “The sooner they can get on precision therapeutics to treat the disease, the better. Outcomes will reflect wait time until you get therapy.”

Northwell treats more New York residents for cancer than any provider in the state, according to the Statewide Planning and Research Cooperative System, inpatient and ambulatory surgery data. 

The center, which is located in Lake Success, started conducting tests several weeks ago.

The lab is using high-end DNA sequencing to extract and define the genomic details of each tumor. Each patient tumor is different, which affects decisions about the best possible treatment.

“When the diagnosis isn’t totally clear to the pathology team, the genetics of the cancer will often inform the diagnosis,” said Boyd. Some patients with the same type of tumor will respond differently to radiation.

The lab is offering four single-gene tests: EGF for non-small cell lung cancer, BRAF for melanoma, KRAS for colorectal, pancreatic and lung cancers, and BRAF/NRAS for melanoma.The MDL plans to offer a 161-gene NGS panel for solid malignancies, a 45-gene NGS panel for hematologic malignancies, and MSI-H, a genetic test that reveals whether tumors will respond to immunotherapy.

Long road

Northwell recruited Boyd to start a molecular diagnostic lab four years ago. He started working in February of 2020, a month before the pandemic caused local, state, national and worldwide disruption.

While he has other responsibilities, Boyd suggested that his “primary reason” for joining Northwell was to “create and direct a Center for Genomic Medicine.”

Northwell conducted extensive physical renovation of the core lab facility that houses the MDL. Northwell also hired six people for the MDL, which includes a lab director, a lab manager, two certified lab technicians, a director of bioinformatics and an LIMS administrator.

In addition, New York State Department of Health had to certify the tests. Northwell is working through certification for additional tests.

Patients don’t need to go to the Lake Success facility to benefit from the services offered by the lab.The cost to patients for these tests is less than it would be for a for profit lab, Boyd said.

“We are a non profit and all we’re looking for is the sustainability of the lab infrastructure,” he added.

At this point, the lab isn’t conducting any germ line testing to determine if there are genetic predispositions to various cancers.

“That might be one of those tests we role out in the future,” Boyd said.

For Boyd, who earned a PhD in toxicology and biochemistry from North Carolina State University in Raleigh, the work is particularly rewarding.

To see his job “impact care tomorrow” based on a particular genetic alteration, “it doesn’t get much better than that for an individual with my background and profession,” he said.

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Camila dos Santos Photo courtesy of CSHL

By Daniel Dunaief

People often think of and study systems or organs in the body as discrete units. 

In a healthy human body, however, these organs and systems work together, sometimes producing signals that affect other areas.

Recently, Cold Spring Harbor Laboratory Associate Professor Camila dos Santos and graduate students Samantha Henry and Steven Lewis, along with former postdoctoral researcher Samantha Cyrill, published a study in the journal Nature Communications that showed a link in a mouse model between persistent bacterial urinary tract infections and changes in breast tissue.

The study provides information about how a response in one area of the body could affect another far from an infection and could provide women with the kind of information that could inform the way they monitor their health.

To be sure, dos Santos and her graduate students didn’t study the processes in humans, which could be different than they are in mice.

Indeed, they are in the process of establishing clinical studies to check if UTIs in women drive breast alterations.

The body’s response

In this research, the scientists demonstrated that an unresolved urinary tract infection itself wasn’t causing changes in breast tissue, but that the body’s reaction to the presence of the bacteria triggered these changes.

By treating the urinary tract infections, Henry and Lewis showed that breast cells returned to their normal state.

Further, when they didn’t treat the UTI but blocked the molecule TIMP1, which causes collagen deposits and milk duct enlargements, the breast cells returned to their normal state.

The TIMP1 role is “probably the main eureka moment,” said Lewis, who is an MD/ PhD student at Stony Brook University. “It explains how an infection in the bladder can change a faraway tissue.”

Lewis suggested that collagen, among other factors, changes the density of breast tissue. When women get a mammography, doctors are looking for changes in the density of their breasts.

Taking a step back from the link, these graduate students and dos Santos considered whether changes in the breast tissue during an infection could provide an evolutionary benefit.

“From an evolutionary standpoint, there should be some adaptive advantage,” suggested Henry, who is earning her PhD in genetics at Stony Brook University and will defend her thesis in July. Speculating on what this might be, she suggested the mammary gland might change in response to an infection to protect milk production during lactation, enabling a mother to feed her young.

Epidemiological studies

A link between persistent UTIs and breast cancer could show up in epidemiological studies.

Dos Santos and collaborators are exploring such questions in the context of European data and are working with US collaborators to collect this information.

In addition, dos Santos believes women should consider how other ongoing threats to their overall health impact their bodies. Women with clinical depression, for example, have worse prognoses in terms of disease. Humans have health threats beyond UTIs that could predispose them to developing cancer, dos Santos said.

Division of labor

Henry and Lewis took over a study that Samantha Cyrill, the third co-first author on the paper started. When Cyrill finished her postdoctoral work, Henry and Lewis “put on their capes and said, ‘We are going to take this to the end line.’ They are incredible people,” said dos Santos.

They each contributed to the considerable work involved.

Henry primarily analyzed the single cell RNA sequencing data, specifically identifying changes in the epithelial compartment. Gina Jones, a visiting CSHL undergraduate research program student, and Lewis also contributed to this.

Henry also participated in TIMP1 neutralizing antibody treatment in post-lactation involution mice, contributing to tissue collection and staining.

Working with Cyrill and Henry, Lewis contributed to the mouse work, including experiments like neutralizing TIMP1 and CSF3. Lewis also worked with Cyrill on the UTI infections in the animals and with Henry in processing tissues for single cell RNA sequencing and assisted Henry on the sequencing analysis.

While this result is compelling and offers an opportunity to study how an infection in an area of the body can trigger changes in another, dos Santos recognized the inherent risk in a new project and direction that could have either been disconnected or a been a dead end.

“It was an incredible risk,” said dos Santos. She was rejected from at least four different funding opportunities because the research is “so out there,” she said. She tapped into foundations and to CSHL for support.

Back stories

A resident of Brooklyn, Lewis was born in Queens and raised in Scarsdale. He joined the dos Santos lab in March of 2021. One of the appeals of the dos Santos lab was that he wanted to understand how life history events drive disease, especially breast cancer.

A big Mets fan, Lewis, whose current favorite payer is Pete Alonso, is planning to run his third marathon this fall.

Lewis is dating Sofia Manfredi, who writes for Last Week Tonight with John Oliver and accepted an Emmy award on behalf of the staff.

Lewis considers himself Manfredi’s “biggest cheerleader,” while he appreciates how well she listens to him and asks important questions about his work.

As for Henry, she grew up in Greenport. She joined the lab in May of 2020 and is planning to defend her thesis in July.

Her father Joseph Henry owns JR Home Improvements and her mother Christine Thompson worked as a waitress and a bartender in various restaurants.

Henry is married to Owen Roberts, who is a civil engineer and works in the Empire State Building for HNTB as a civil engineer, where he focuses on traffic.

Henry hopes to live in Boston after she graduates. She’s adopted the rooting interests of her husband, who is a fan of Beantown teams, and will support the Bruins and the Celtics. A lifelong Yankees fan, however, Henry, who watched the Bronx Bombers with her father growing up, draws the line at supporting the “Sawx.”

As for the work, Henry and Lewis are excited to see what the lab discovers in the next steps.

“I do think this work is extremely informative, defining a relationship between an infection, UTI, and the mammary gland that has not previously been appreciated,” Henry explained.

“This provides information to the public,” said Henry. “I always think it is worth knowing how different events may impact your body.”

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F. William Studier, senior scientist emeritus at Brookhaven National Laboratory, in 2004. (Roger Stoutenburgh/Brookhaven National Laboratory)

Prestigious honor recognizes development of widely used protein- and RNA-production platform

F. William Studier, a senior biophysicist emeritus at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory, has won the 2024 Richard N. Merkin Prize in Biomedical Technology [https://merkinprize.org/] for his development in the 1980s of an efficient, scalable method of producing RNA and proteins in the laboratory. His “T7 expression” technology can be used to make large quantities of nearly any RNA or protein and has been for decades, and continues to be, a mainstay of biomedical research and pharmaceutical production. Studier’s approach has been used to produce numerous therapeutics, diagnostics, and vaccines — including the COVID-19 mRNA vaccines credited with extending millions of lives in recent years [see: https://www.bnl.gov/newsroom/news.php?a=218806].

“F. William Studier’s brilliant work on the T7 system transformed biomedicine, saving millions of lives globally and improving the chances for further research that will change healthcare delivery,” said Dr. Richard Merkin, CEO and founder of Heritage Provider Network, one of the country’s largest physician-owned integrated health care systems. “His work exemplifies why I created this prize initiative that honors and showcases amazing innovators like Bill. I’m honored to be celebrating his remarkable achievements.”

The Merkin Prize, inaugurated in 2023, recognizes novel technologies that have improved human health. It carries a $400,000 cash award and is administered by the Broad Institute of MIT and Harvard, one of the world’s leading biomedical research institutes. All nominations for the 2024 Merkin Prize were evaluated by a selection committee composed of nine scientific leaders from academia and industry in the U.S. and Europe. Studier will be honored in a prize ceremony held on Sept. 17, 2024.

“The T7 system has been influential in biomedicine and has had important clinical implications for many years, but Bill Studier’s contribution to the field has really not been as celebrated as it ought to be,” said Harold Varmus, chair of the Merkin Prize selection committee. Varmus is also the Lewis Thomas University Professor at Weill Cornell Medicine, a senior associate at the New York Genome Center, and a recipient of the Nobel Prize in Physiology or Medicine for his work on the origins of cancer.

“Bill Studier’s development of T7 phage RNA polymerase for use in preparing RNA templates for multiple uses in research labs worldwide has been a truly revolutionary technical advance for the entire field of molecular biology,” said Joan Steitz, the Sterling Professor of Molecular Biophysics and Biochemistry at Yale University.

“Today, virtually every protein you want to produce in bacteria is made with a T7 system,” said Venki Ramakrishnan of the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, and a winner of the 2009 Nobel Prize in Chemistry. “There’s not a single molecular biology or biochemistry lab I know that doesn’t use T7.”

“This award is a great honor for Bill Studier, recognizing the significance of the research and technology he pioneered. It reinforces how basic research — asking fundamental questions about the way the world and everything in it works — can result in important and unexpected advances that continue to have impact even decades after the initial discoveries,” said Brookhaven National Laboratory Director JoAnne Hewett. “It is fabulous to see Bill recognized for his lifetime of work and the critical role it has played in biotechnology and medicine.”

Studier’s T7 expression system uses the T7 promoter to “turn on” a gene of interest and the T7 RNA polymerase to transcribe that gene into messenger RNA (mRNA) so that E. coli ribosomes can use the RNA-encoded information to synthesize the desired protein. The system can also be used to make desired mRNAs as, for example, was done to make the COVID-19 mRNA vaccines. (Tiffany Bowman/Brookhaven National Laboratory)



Driven by basic biology

Studier grew up in Iowa and became fascinated with biophysics while an undergraduate at Yale University. Then, during graduate school at the California Institute of Technology in the early 1960s, he was introduced to bacteriophage T7, a virus that infects Escherichia coli bacteria. He wondered how T7 could so effectively and quickly take over E. coli, rapidly turning the bacterial cells into factories to produce more copies of itself. That question launched a career focused on the basic biology of T7.

“I’ve always been interested in solving problems,” Studier told Brookhaven National Laboratory in a 2011 profile [https://www.bnl.gov/newsroom/news.php?a=22241]. “The motivation for my research is not commercial application. My interest is in basic research.”

When he joined Brookhaven Lab in 1964, Studier focused on sequencing the genes of the T7 bacteriophage and understanding the function of each of its corresponding proteins during infection of E. coli. By 1984, he and Brookhaven colleague John Dunn successfully identified and cloned the protein within T7 that was responsible for rapidly copying T7 DNA into many corresponding strands of RNA [see: https://www.pnas.org/doi/10.1073/pnas.81.7.2035]. RNA is the molecule that instructs cells which amino acids to link up to build a particular protein — a critical step in protein synthesis and therefore the bacteriophage’s ability to infect E. coli.

Studier realized that the protein, called the T7 RNA polymerase, might be able to quickly and efficiently produce RNA from not only T7 DNA but also from the genes of any organism. If a gene was tagged with a special DNA sequence, known as the T7 promoter, then the T7 RNA polymerase would latch on and begin copying it. In 1986, Studier described this system in the Journal of Molecular Biology [https://pubmed.ncbi.nlm.nih.gov/3537305/].

“His work really illustrates that sometimes a remarkable technology can emerge not only from people trying to build technologies but from someone who is trying to use basic science to understand a fascinating biological phenomenon,” Varmus said.

Speeding science

Before Studier’s development of the T7 system, scientists who wanted to produce RNA or proteins generally inserted the genes into the natural E. coli genome and let the E. coli polymerase produce the corresponding RNA at the same time as the bacteria produced its own RNA and proteins. But the E. coli machinery was relatively slow, and scientists often ran into problems with the bacteria turning off their DNA-reading programs. T7 polymerase overcame both these problems: It was far faster, and E. coli had no built-in way to shut it off.

Within a few years, biologists had rapidly switched from their older methods to the T7 system for producing both RNA and proteins. When proteins are the desired end result, the E. coli molecular machinery for translating mRNA into proteins is used after the T7 system makes the RNA.

Studier continued studying the T7 polymerase and promoter, fine-tuning the system for years and publishing new improved versions as recently as 2018.

As of 2020, the T7 technology had been cited in more than 220,000 published studies, with 12,000 new studies using the technology published each year. There are more than 100 different versions of the T7 technology available commercially and 12 patents in Studier’s name related to the system.

Making medicine

The T7 technology has also had immediate impacts in industry, with more than 900 biotech and pharmaceutical companies licensing it to produce therapeutics and vaccines.

In 2020, scientists used the T7 platform to produce enough mRNA for COVID-19 vaccines to vaccinate millions of people in the U.S. and around the world. With the T7 promoter placed next to the gene for the COVID-19 spike protein, the T7 polymerase could generate many kilograms of mRNA — the active molecule in the vaccines — at a time.

“I think it’s an incredible testament to this technology that, decades after its development, it’s still the go-to method for RNA and protein production,” said John Shanklin, a distinguished biochemist and chair of the Biology Department at Brookhaven National Laboratory, who considered Studier a mentor for many years.

Those who know Studier say the Merkin Prize is well-deserved; Studier changed the course of biomedicine while working quietly on basic science questions that interested him.

“Almost no one has heard of Bill Studier because he is a quiet, modest guy who had a small lab,” said Ramakrishnan, who worked with Studier at Brookhaven in the 1980s. “But he is an absolutely fantastic role model of what a scientist should be like.”

“He has flown under the radar and hasn’t been recognized for his accomplishments very much,” Shanklin agreed. “This is a well-deserved honor.”

Studier was also committed to guaranteeing access to his technology. When Brookhaven was in the process of licensing and commercializing the T7 system shortly after its development, Studier ensured that it remained free for academic labs while charging commercial licensing fees to companies.

F. William Studier earned a bachelor’s degree in biophysics from Yale in 1958, followed by a Ph.D. from the California Institute of Technology in 1963. He worked as a postdoctoral fellow in the Department of Biochemistry at Stanford University School of Medicine, and then he joined Brookhaven Lab’s Biology Department in 1964 as an assistant biophysicist. Over the years, Studier rose through the department’s ranks, receiving tenure in 1971 and becoming a tenured senior biophysicist in 1974.

He served as chair of the Biology Department from 1990 to 1999 and then returned to research. He also served as an adjunct professor of biochemistry at Stony Brook University. His achievements have been recognized by election to the American Academy of Arts and Sciences in 1990, the National Academy of Sciences in 1992, and as a Fellow of the American Association for the Advancement of Science in 2007. He retired from the Lab in 2015 and was named senior scientist emeritus. In 2018, he was elected as a Fellow of the National Academy of Inventors. He holds 15 patents of which nine have been licensed and commercialized, including those on the T7 system.

Studier’s research at Brookhaven Lab was supported by the DOE Office of Science.


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Gabrielle Pouchelon with technician Sam Liebman. Photo by Constance Brukin/CSHL

By Daniel Dunaief

Gabrielle Pouchelon doesn’t need to answer the age-old debate about heredity vs. environment. When it comes to the development of the brain, she’s studying the response both to sensory cues and genetics.

Gabrielle Pouchelon.
Photo courtesy of CSHL

An Assistant Professor who joined Cold Spring Harbor Laboratory in March of 2022, Pouchelon studies the interplay between sensory and neuromodulatory inputs and genetic programs in circuit maturation. She also studies other neuromodulatory inputs, usually associated with states of adulthood, which could control development.

A combination of genetics and environment shapes the way neurons connect in a healthy brain. In people who develop non-neurotypical behaviors, through autism, schizophrenia or other conditions, the development of neurological connections and architecture is likely different.

Researchers have associated genes of susceptibility with schizophrenia and autism spectrum disorders. Scientists believe environmental cues provide the brain with activity that interact with these genetic components.

“We are trying to understand whether we can [intervene] earlier that can have different outcomes at later times,” said Pouchelon. “We are studying ways to intervene with these transient processes and examine whether dysfunctions associated with the disorders are improved.”

During critical periods of development, the brain has a high level of plasticity, where various inputs can alter neurons and their connections. This not only involves building connections, but sometimes breaking them down and rebuilding other ones. As people age, that plasticity decreases, which is why children learn faster than adults in areas such as the acquisition and development of language skills.

While the timing of critical periods is less well-defined in humans and language is a complex function, the ability to learn new languages at a young age reflects the high plasticity of the brain.

Scientists are studying language processes, which are specific to humans, with functional magnetic resonance imaging.

Pouchelon, who isn’t studying language skills, hopes that understanding the architecture of developing brains and how they respond to sensory and neuromodulatory cues could shed light on the studies performed in humans. Since behavioral therapy and pharmaceutical treatments can help children with autism, she believes understanding how external cues affect genetic elements could uncover drug targets to alleviate symptoms of neurodevelopmental disorders at an early age.

Neurons & the environment

From left, technician Sam Liebman, Gabrielle Pouchelon and postdoctoral researcher Dimitri Dumontier. Photo courtesy of Gabrielle Pouchelon

In her lab, which currently includes three researchers but she expects to double within a month, Pouchelon uses sophisticated tools to target not only the effect of the environment, but also to look at the specific neurons that transmit information.

She is trying to “understand at a very precise level what a sensory input means and what are the neurons that integrate that sensory input.”

Sam Liebman, who became a technician in Pouchelon’s lab two years ago after graduating from the University of Vermont, appreciates the work they’re doing and her mentorship.

The lab is “unique and special” because he has that “close relationship” in what is now a smaller lab with Pouchelon, Liebman said.

Growing up in Huntington, Liebman, who hopes to go to graduate school in the fall of 2025, came to Cold Spring Harbor Laboratory for field trips in middle school and high school.

“I idolized this place and this campus,” said Liebman.

Pouchelon has asked for Liebman’s opinion on potential candidates to join the lab, even summer interns.

Fragile X Syndrome

Most of the work Pouchelon conducts is done on animal models. She is mainly studying animals with a mutation linked to Fragile X Syndrome. 

In Fragile X Syndrome, which can affect boys and girls, children can have developmental delays, learning disabilities and social and behavioral problems. Boys, according to the Centers for Disease Control and Prevention, typically have some degree of intellectual disability, while girls can have normal intelligence or some degree of intellectual disability.

Other models for autism exist, such as genetic mutations in the gene Shank3. “We are trying to utilize these models to apply what we understand of development in brains that are healthy and compare them” to the mutated models, Pouchelon explained.

While clinical trials are exploring receptors as drug targets for Fragile X Syndrome, she hopes to find new ones that are selective in early stages of the disease to modify their use depending on the stages of development.

An annoying nerd

Born and raised in Paris, France to a family that showed considerably more artistic talent than she, Pouchelon struggled with games she and her sisters played when they listened to music on the radio and they had to guess the composer.

“I was the one always losing,” said Pouchelon. Her family, including her two older sisters who currently live in France, knew “way more about art and history than I did. I was the nerd scientist.”

When she was young, she was curious and asked a lot of “annoying questions” because she was interested in the “mystery of everything.” In high school, she became interested in the brain.

Pouchelon, who isn’t actively searching for French food but finds the baguettes at the Duck Island Bakery exceptional, lives on the Cold Spring Harbor Laboratory campus with her husband Djeckby “DJ” Joseph, a naturalized American citizen originally from Haiti who works in law enforcement at the VA Hospital in Manhattan, and their two-year old son Theo.

Eager to ensure her son benefits from a multicultural identity, Pouchelon speaks to Theo in French. He also attends on campus day care, where he learns English.

As for the decision to come to Cold Spring Harbor Laboratory, Pouchelon, who conducted her PhD research at the University of Geneva in Switzerland and completed her postdoctoral research at New York University and at Harvard Medical School, is thrilled to discuss her work with the talented and collegial staff at the lab.

Cold Spring Harbor Laboratory, which is known internationally for meetings and courses, is an “exciting place” where scientists conduct cutting edge research.

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