About halfway down Cold Spring Harbor Laboratory’s (CSHL’s) Bungtown Road, right next to the volleyball court, you’ll find a living snapshot of the area’s diverse ecosystem.

It’s called Frog Pond. And while its namesake is often easy to find there, frogs aren’t the pond’s only inhabitants. On any given day, passersby may encounter dragonflies, geese, ducks, turtles, toads, and more. Duckweed and other aquatic plants blanket the pond’s muddy waters. Trees left over from the 1986 construction of Grace Auditorium stand tall near the water’s edge. It might come as a surprise to learn that Frog Pond has another thing in common with the auditorium. Both are man-made.

Before 1988, there was no Frog Pond. That year, CSHL finished a project to restore some of Bungtown Road’s mid-century aesthetic by replacing its telephone poles with underground wiring.

“In the summer of 1948, this then-sylvan path had a rural quality that reflected what Long Island must have been like in the 19th century,” CSHL’s 1988 Annual Report (pdf) states.

Frog Pond’s native species aren’t the only amphibians you’ll find at CSHL. Since 1993, Xenopus, the African clawed frog, has helped countless scientists learn about the origins and mechanics of life through CSHL’s Cell & Developmental Biology of Xenopus: Gene Discovery & Disease Course.

For over three decades, Frog Pond has served as a retention basin to manage stormwater runoff and help prevent flooding. These days, it is also a key source of duckweed for the Martienssen lab’s biofuel research happening across the street. But the pond is still perhaps best known in the CSHL community as a place to relax and catch a glimpse of the frogs and turtles that frequent the area.

CSHL Horticulturist Riley McKenna agrees. “The biggest feature of the pond is its wildlife,” he says. “Most mornings I see some kind of action happening from some kind of bird, groundhog, or turtle.”

Frog Pond is fed from above by a small stream and several lesser ponds before continuing underground into Cold Spring Harbor. The surrounding willow oaks, dogwoods, and winterberry bushes provide shade and a source of food for any animals that may stop by.

“I visit it nearly weekly throughout the year to search for whatever reptiles and amphibians might be hanging out, but also to admire the change in seasons,” says CSHL Professor Zachary Lippman, who took most of the photos in this story. “The arrival of spring especially brings all these great animals out again, and we get to enjoy the pollywogs going from tadpoles to frogs before our eyes.”

For McKenna, the pond and its surroundings also offer a sense of peace and serenity. “A landscape would be nothing without its environment,” he says. “I think that’s what makes the lab, the lab—the environment around us. Long Island is an island like no other.”

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In a sense, each of us begins life ready for action. Many animals perform amazing feats soon after they’re born. Spiders spin webs. Whales swim. But where do these innate abilities come from? Obviously, the brain plays a key role as it contains the trillions of neural connections needed to control complex behaviors. However, the genome has space for only a small fraction of that information. This paradox has stumped scientists for decades. Now, Cold Spring Harbor Laboratory (CSHL) Professors Anthony Zador and Alexei Koulakov have devised a potential solution using artificial intelligence.

When Zador first encounters this problem, he puts a new spin on it. “What if the genome’s limited capacity is the very thing that makes us so smart?” he wonders. “What if it’s a feature, not a bug?” In other words, maybe we can act intelligently and learn quickly because the genome’s limits force us to adapt. This is a big, bold idea—tough to demonstrate. After all, we can’t stretch lab experiments across billions of years of evolution. That’s where the idea of the genomic bottleneck algorithm emerges.

In AI, generations don’t span decades. New models are born with the push of a button. Zador, Koulakov, and CSHL postdocs Divyansha Lachi and Sergey Shuvaev set out to develop a computer algorithm that folds heaps of data into a neat package—much like our genome might compress the information needed to form functional brain circuits. They then test this algorithm against AI networks that undergo multiple training rounds. Amazingly, they find the new, untrained algorithm performs tasks like image recognition almost as effectively as state-of-the-art AI. Their algorithm even holds its own in video games like Space Invaders. It’s as if it innately understands how to play.

An AI-simulated cheetah cannot move forward on its own without training. Press play to see how it does with the genomic bottleneck algorithm.

Does this mean AI will soon replicate our natural abilities? “We haven’t reached that level,” says Koulakov. “The brain’s cortical architecture can fit about 280 terabytes of information—32 years of high-definition video. Our genomes accommodate about one hour. This implies a 400,000-fold compression technology cannot yet match.”

Nevertheless, the algorithm allows for compression levels thus far unseen in AI. That feature could have impressive uses in tech. Shuvaev, the study’s lead author, explains:

“For example, if you wanted to run a large language model on a cell phone, one way [the algorithm] could be used is to unfold your model layer by layer on the hardware.”

Such applications could mean more evolved AI with faster runtimes. And to think, it only took 3.5 billion years of evolution to get here.

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More than two million new cases of cancer will be diagnosed in the United States in 2024, according to the National Cancer Institute. Range Cancer Therapeutics ETF (Nasdaq: CNCR) is partnering with Cold Spring Harbor Laboratory (CSHL) to highlight CSHL’s pioneering role in advancing cancer research. Through the partnership, 23% of revenues generated by fees from CNCR will be donated to CSHL quarterly.

Bringing together the powers of philanthropy and investing, Range ETFs and CSHL announced this unique affiliation with a historic event at the Nasdaq stock market on November 14, 2024. The event featured a powerful visual display on the Nasdaq tower, and Range ETFs and CSHL leadership and guests gathered on the iconic Nasdaq podium to mark this momentous occasion.

“Cold Spring Harbor Laboratory is one of only seven national basic biological research cancer centers designated by the National Cancer Institute in Washington DC. Cancer research is fundamental to our discovery efforts,” said CSHL President and CEO Bruce Stillman. “The institution is investing heavily in the growth of our cancer program, specifically in multidisciplinary, collaborative ventures as part of our new brain-body physiology initiative.”

Range ETFs CNCR ETF focuses on companies dedicated to cancer research, treatment, and therapeutics, offering investors targeted exposure in this vital sector. It is purpose-built to provide exposure to a wide range of cancer therapeutic modalities.

“The contribution from Range will directly benefit the research efforts at CSHL, underscoring our commitment to advancing scientific innovation in oncology therapeutics,” said Range ETFs founder and CSHL Association Board Member, Tim Rotolo. “CNCR ETF provides exposure to nearly the entire lifecycle of drug development and distribution, and this new collaboration with CSHL provides an opportunity for investors to also see their money go toward the earliest stages of cancer breakthroughs.”

Stillman added that unique partnerships like this provide opportunities to engage with people who are already committed to scientific advancement and maximize efforts to support cancer research in unique ways.

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The opportunity to turn curiosity into discoveries that impact the human condition is at the core of Cold Spring Harbor Laboratory’s mission. Our scientists are empowered to ask big questions and search for solutions to biology’s most challenging problems. Doing that requires interdisciplinary study, and the Laboratory’s brain-body physiology program encourages our scientists to confront today’s toughest health challenges from multiple fronts collectively. Understanding the connections between our minds and our bodies and their effect on physiological homeostasis has the potential to lead to revolutionary medical interventions that will enable us to remain healthy as we age.

In this issue of Harbor Transcript, we share CSHL’s latest research into brain-body connections relevant to aging, breast cancer, menopause, pregnancy, and more. Our cover story sheds light on important topics that remain understudied. It is well known that historical underrepresentation of research on women’s health has resulted in a limited understanding of how women experience disease and respond to treatment. Associate Professors Camila dos Santos and Jessica Tollkuhn exemplify researchers at Cold Spring Harbor working to change this dynamic.

Another highly misunderstood condition is autism spectrum disorder. With generous support from the Simons Foundation, Professors Michael Wigler and Ivan Iossifov have combined their expertise in molecular biology and computer science to explore large datasets of genetic variants associated with autism. By pinpointing and cataloging these variants, they’ve given medical professionals the tools to diagnose autism and provide potentially life-altering interventions sooner.

While CSHL scientists work diligently to understand complex brain-body interactions, we also function as a global hub for cutting-edge science, which is why our Meetings and Courses Program, Banbury Center, DNA Learning Center, and Center for Humanities are critical to the future of science. Education and discovery go hand in hand. Indeed, we have added new scientific meetings that focus on brain-body interactions, whole-organism physiology, and the aging processes.

No one better understood that connection than Jim Simons, honorary trustee, longtime supporter of the Laboratory, and husband to our Board of Trustees Chair, Marilyn Simons. Though we lost a dear friend this year, his life was a testament to the power of living in service to the community, and his legacy will live on through the programs and people he and Marilyn have touched. We are forever grateful for Jim’s transformational commitment.

We appreciate all those who have joined Cold Spring Harbor throughout the year at events, meetings, tours, or simply by visiting our website. Cold Spring Harbor is a unique place that brings together people who want to leave the world a little better than we found it, and we appreciate you taking this journey with us.

—Bruce Stillman, Ph.D.
“President’s Message”
Harbor Transcript, Volume 44, Issue 2

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On November 14, Cold Spring Harbor Laboratory (CSHL) held its 19th annual Double Helix Medals dinner (DHMD) at the American Museum of Natural History in New York City. The event, emceed by CBS journalist Lesley Stahl, honored Alisa and Daniel Doctoroff and 2023 Nobel laureate Dr. Katalin Karikó. With the support of the event chairs and donors, the gala raised $7 million for biology research and education at CSHL.

Alisa and Daniel Doctoroff are leaders of Target ALS, an innovative nonprofit that has sparked dramatic progress in research on amyotrophic lateral sclerosis (ALS). Before being diagnosed with this neurodegenerative disease, Mr. Doctoroff served as New York City Deputy Mayor for Economic Development and Rebuilding and as CEO and president of Bloomberg L.P. He is the founder and board chair of Target ALS.

“My goal for Target ALS is our mission statement, ‘Everyone lives.’ We are in sight of that goal,” says Mr. Doctoroff. “We can see the day coming, and there are smaller goals that will get us there,” adds Mrs. Doctoroff. “We are, one by one, achieving and attacking those goals and getting to the point where everyone lives with ALS.”

Dr. Katalin Karikó is a winner of the 2023 Nobel Prize in Physiology or Medicine and a professor at the University of Szeged in Hungary. Her revolutionary biomedical advancements at the University of Pennsylvania and later at the pharmaceutical company BioNTech created the blueprint for mRNA vaccines, saving millions of lives. Despite this success, she remains humble as ever.

“Getting a Nobel Prize, I realized that attention is on the science and the scientist,” Dr. Karikó says. “I receive a lot of awards, but every time, I emphasize that a lot of scientists contributed. I want to be remembered as an honest, cheerful, happy scientist. That’s it.”

The 2024 DHMD was chaired by Dr. Neri Oxman and Mr. William Ackman, Ms. Jamie Nicholls and Mr. O. Francis Biondi, Mr. and Mrs. David Boies, Dr. Albert Bourla and Pfizer, Inc., Ms. Barbara Amonson and Dr. Vincent Della Pietra, Drs. Pamela Hurst-Della Pietra and Stephen Della Pietra, Mr. and Mrs. John Desmarais, Mr. and Mrs. Jeffrey E. Kelter, Dr. and Mrs. Tomislav Kundic, Mr. and Mrs. Robert D. Lindsay, Ms. Ivana Stolnik-Lourie and Dr. Robert Lourie, Dr. Marcia Kramer Mayer, Dr. and Mrs. Howard L. Morgan, Mr. and Mrs. Tom Secunda, Dr. Marilyn H. Simons, and Mr. and Mrs. Paul J. Taubman.

Since 2006, the DHMD has raised over $67 million to support CSHL’s research and education programs.

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How do you turn a small but influential science education outpost into one of the world’s leading destinations for breakthrough bioscience? It takes a village.

This year marks the centennial anniversary of the formation of the Cold Spring Harbor Laboratory Association (CSHLA). Formerly known as the Long Island Biological Association (LIBA), the CSHLA is a remarkable group with a remarkable history. Though founded in 1924, its origins lie in the 19th century.

The early years

In 1890, the Brooklyn Institute of Arts and Sciences (BIAS) established the Biological Laboratory at Cold Spring Harbor as a summer school for training biology teachers and students. Early courses covered topics such as zoology, variation and inheritance, embryology, bacteriology, and ecology. Initially housed in the New York State Fish Hatchery, the Laboratory moved across the road to land provided by the Jones family, which later set up a nonprofit corporation called the Wawepex Society to hold a title for the property. New Yorkers will recognize the name ‘Jones’ for its connection to Jones Beach. The phrase “keeping up with the Joneses” also refers to this family.

Through the beginning of the 20th century, the Laboratory’s relationship with BIAS became increasingly fraught. Things came to a head in 1914 when the director of the Laboratory threatened to resign. In response, the Laboratory was made a department of BIAS. Then, in 1917, efforts were renewed to create an endowment for the Laboratory. Through the generosity of a small number of local supporters—including Louis Comfort Tiffany, William John Matheson, Walter Jennings, August Heckscher, and Cornelia Prime—the remarkable sum of $27,000 was raised in just eight months. To put that in context, $27,000 in 1917 equals about $700,000 in 2024.

At this point, the Laboratory’s director was also running two additional institutes on the Cold Spring Harbor campus. In 1921, he resigned from his post, citing these other responsibilities. However, he suggested various measures to mitigate such conflicts moving forward. In particular, he advocated for BIAS to hand over control of the Biological Laboratory at Cold Spring Harbor to an association of neighbors. The group would include those local residents who’d so generously contributed to the 1917 endowment. There would be a new director and a scientific advisory board to offer guidance. BIAS raised no objections to this proposal, and a charter was drawn up for the Long Island Biological Association.

In August 1923, a local organization of neighbors voted to form the Association. On February 18, 1924, LIBA was incorporated. One week later, the first meeting of the Board of Directors was held. The group adopted bylaws and appointed Dr. Reginald Harris as its founding director. On March 12, the Brooklyn Institute formally turned over its buildings along with its endowment and scholarship funds. The Wawepex Society transferred ownership of Jones Laboratory and drafted a 50-year lease for the grounds.

The 1924 Biological Laboratory Annual Report (pdf) listed LIBA’s first members. There were six “Founding Members” and 19 “Patrons” who each contributed $5,000 and $500, respectively. There were also more than 170 “Sustaining Members” whose combined contributions totaled $1,700. The membership list includes such illustrious names as J.P. Morgan, W.K. Vanderbilt, Marshall Field III, Henry De Forest, Charles Frick, Walter James, Mrs. Otto Kahn (Addie Wolff), August Heckscher, and Louis Tiffany.

LIBA’s importance to the Biological Laboratory became immediately apparent. In 1926, LIBA members raised the funds needed to purchase 32.5 acres of land adjacent to the Laboratory. The following year, Mr. and Mrs. Acosta Nichols donated $12,000 for the construction of a lab in memory of their son George, who had taken part in a nature studies class held on campus.

LIBA also became known across the region for its impressive “Gold Coast” galas. One example took place in 1932. It was during this year that the Field family held a grand fundraising event at Caumsett, their estate in Lloyd Harbor, NY. Attended by celebrities such as Fred Astaire, the gala included activities like dancing and china breaking. (“China breaking” is exactly what it sounds like. The activity was overseen by prominent businessman Vincent Astor.) All told, the event raised over $4,500—i.e., $99,000 in 2024 dollars. Through the 1940s and 1950s, LIBA members contributed between 7% and 10% of the Biological Laboratory’s income.

The modern era

LIBA’s modern era began in 1962 when the institute we now know as Cold Spring Harbor Laboratory first took the name of its neighboring community. It was during this year that the Carnegie Institution closed the Department of Genetics. Its land and buildings were combined with those of the Biological Laboratory to create the Cold Spring Harbor Laboratory of Quantitative Biology. (The name would be shortened to Cold Spring Harbor Laboratory in 1970.) LIBA did not have any direct responsibility for governing the new institute. However, the Association did retain two places on the new Board of Trustees. It now fully devoted itself to ambassadorship and fundraising. And it accomplished these goals with great success.

For example, in 1972, LIBA Chairman Edward Pulling led a campaign that raised $250,000 for a new addition to Jones Laboratory. A few years later, he helped raise $225,000 to build a new Williams House and another $200,000 to purchase land still owned by the Carnegie Institution.

In one historic gift, LIBA contributed $600,000 toward the cost of the Oliver and Lorraine Grace Auditorium. Grace is the primary venue for CSHL’s world-renowned Meetings & Courses Program. This program has brought hundreds of thousands of leading scientists to Cold Spring Harbor. Here, they’ve discussed their latest research, shared ideas with potential collaborators, and planted the seeds of countless breakthroughs. So, while $600,000 may sound like a lot, there’s really no way to quantify the return on this investment.

In 1992, LIBA officially became the Cold Spring Harbor Laboratory Association (CSHLA). The Association has since furthered its mission to provide CSHL with much-needed philanthropic support. Over the past 10 years, CSHLA members have helped raise an extraordinary $80 million in unrestricted funding for the Laboratory. Indeed, many of the labs and other facilities found across campus today owe their existence to CSHLA members.

Of course, a lot has changed since the early days. After all, today’s Association gatherings are unlikely to break out in spontaneous bouts of china breaking. Nevertheless, CSHLA continues to bring some of Long Island’s best and brightest together for a worthy cause. Current Association Directors include acclaimed actress Susan Lucci and the late best-selling novelist Nelson DeMille, among many other prominent community members.

For over 100 years, LIBA and CSHLA have played an essential role in supporting the advancement of science at Cold Spring Harbor. Its members and their community have transformed a small summer school into one of the world’s most renowned institutes for cutting-edge science research and education. This is a proud legacy, to say the least—one that holds great promise and potential for the next 100 years.

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If there’s one thing cancer knows, it’s growth. Over the last two decades, scientists have observed that many cancers progress by activating a set of proteins called YAP and TAZ, which control cell growth and organ size. When left uncontrolled, YAP/TAZ can lead to tumor formation. So, if you’re looking for new drug targets, why not start there? Targeting them directly, while possible, remains a challenge. Now, Cold Spring Harbor Laboratory Professor Christopher Vakoc and postdoc Olaf Klingbeil have found a workaround. They’ve successfully tested their new approach in the lab against some of the most common and deadly cancers.

Previous research aimed to target YAP/TAZ molecular interactions and directly inhibit their tumor-promoting function. Vakoc’s team wanted to find another way to go after them. Using a CRISPR screening strategy, they discovered that YAP and TAZ rely heavily on a second set of proteins called MARK 2 and MARK 3. Rather than interfering with the functions of YAP/TAZ directly, targeting MARK 2/3 reactivates their natural ‘off’ switch, called the Hippo signaling pathway.

“We found a way to engage YAP/TAZ earlier,” Klingbeil says. “MARK 2/3 inhibition can reactivate a suppressor pathway normally used by healthy cells, thereby preventing them from going to the nucleus and being active.”

Last year, Vakoc’s team transformed rhabdomyosarcoma cells into healthy muscle cells—a major advancement. However, this treatment strategy, known as differentiation therapy, is still a long way from the clinic. MARK 2 and MARK 3, on the other hand, are druggable targets, and their activity in a wider range of tumors will hopefully generate interest among pharmaceutical companies. Vakoc explains:

“This is a target for rare pediatric sarcomas that we’re very passionate about trying to solve. It’s also relevant in breast cancer. It’s relevant in lung cancer. It’s relevant in pancreatic cancer. Some of the most common human cancers and uncommon human cancers share this addiction to YAP/TAZ.”

Vakoc and Klingbeil found that by reactivating YAP/TAZ’s off switch, tumors don’t just stop growing. They actually shrink, and the cancer begins to disappear. The Vakoc lab now has a new drug target in its sights. In time, that could mean more effective treatments for thousands of patients and new hope for parents who want only to see their kids grow up healthy and cancer-free.

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Diseases can spread rapidly, but now, so can the knowledge needed to stop them. A new information-sharing platform seeks to help slow the spread of infectious diseases. It’s called the Pathogen Data Network (PDN). And it just might help stop the next pandemic before it can start.

Cold Spring Harbor Laboratory’s DNA Learning Center (DNALC) is part of a global consortium of research institutions that have received $2.7 million from the National Institute of Allergy and Infectious Diseases to build the PDN. Their mission: improve pandemic response worldwide by providing open access to shared resources and data on all pathogens affecting humans.

One key component is a new outreach and training program from the DNALC. The program will train undergraduate educators in disease-tracking techniques that could help prevent future pandemics. Importantly, it will focus on institutions in those communities often hit hardest by public health crises.

“This partnership is a natural fit for us,” says DNALC Assistant Director of Diversity and Research Readiness Jason Williams. “We bring the latest technologies and teaching approaches for working with DNA into classrooms around the world. Sharing scientific knowledge and resources worldwide will empower future generations to respond to potential outbreaks sooner, thereby saving lives.”

The PDN builds upon and expands the successful European COVID-19 Data Platform. Led by the Swiss Institute of Bioinformatics and the UK’s European Bioinformatics Institute, the PDN also includes organizations in South Africa and throughout Europe.

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This Halloween, we’re casting our jack-o-lantern light on five of CSHL’s oldest buildings. So, come join us as we cross the threshold into the past.

Jones Laboratory

Tales tell of a Welsh privateer who, after a life of high-seas adventure, settled on the south shore of Long Island. In time, his family would come to own thousands of acres stretching from Massapequa to Oyster Bay. His name lives on long after his passing. You may have heard of Jones Beach. Though the famous state park was named for Major Thomas Jones, it’s his great-great-grandson whose name graces CSHL’s oldest science building.

Jones Laboratory is the longest continuously operating research laboratory in the United States. This National Historic Landmark has stood virtually unchanged for over 130 years—at least on the outside. What began as the second home of CSHL’s earliest courses and education programs now houses the Lippman lab’s revolutionary plant genetics research. Over the years, Jones has withstood hurricanes, blizzards, floods, and more. But its bones are strong and today, this old soul remains as resilient as ever.

Carnegie Library

From 1890-1904, the Brooklyn Institute’s Biological Laboratory held the sole claim to science on the shores of Cold Spring Harbor. That changed at noon on June 11, 1904. Just south of Jones Laboratory, a new building and research organization opened along the shore. The Carnegie Institution of Washington’s Station for Experimental Evolution was “destined to be the leading center of biological research in the world,” according to the Brooklyn Institute’s W.H. Hooper.

Unlike the Biological Laboratory, the Station for Experimental Evolution primarily focused on research. Outside the building, botanist George Shull planted the crops he would later use to develop the first strains of “hybrid vigor” corn. Inside, the three-story building boasted rooms for breeding insects, birds, and aquatic animals, as well as research labs and a library.

Over the years, the Station’s main building would undergo several rounds of renovations. The breeding rooms were gone by 1911. In 1953, the research laboratories would follow. All that remained was the library. Since then, what was once a small collection of research texts has evolved into CSHL’s Library and Archives. The treasure trove of science history now contained within its walls includes, among other things, the personal collections of no fewer than five Nobel laureates.

Wawepex

Layers of history lurk beneath the unassuming facade of the Wawepex Building. Perhaps no other CSHL building can claim as many connections to the area. Its name comes from the original Native American settlement that stood at Cold Spring Harbor. Loose translations include “at the place of the good spring water” and “good little water place.” The Jones family’s Cold Spring Whaling Company constructed the building in the early 19th century to store barrels of whale oil. While in storage, these barrels would be plugged with bungs. Hence, even today the street passing through CSHL’s main campus bears the name Bungtown Road. Alas, all things must pass. The death of the whaling industry in the 1860s brought Jones’ company down with it.

In 1893, John D. Jones’ Wawepex Society leased the old storage building to the Biological Laboratory. Renovations replaced the warehouse with a dark room, lecture hall, operating room, and additional storage space. Wawepex has worn several masks since then. It’s been a dormitory, research building, administration offices, and even the headquarters of a children’s nature program. Today, it’s home to CSHL’s Office of Sponsored Programs. The Office plays a key role in facilitating and managing the grants and other funding avenues that make CSHL’s groundbreaking research possible.

Blackford Hall

By 1906, the Biological Laboratory’s curriculum included 10 courses and several specimen-collecting excursions. As useful as they were, Jones Laboratory and the Wawepex Building could no longer contain it all. As fate would have it, the widow of the Laboratory’s earliest benefactor, Eugene C. Blackford, would come to the rescue. Francis Blackford approached the Biological Laboratory that year with a “desire to erect a substantial building on the lands of the Laboratory … to provide a comfortable home for the faculty of the school and their families, and the young women pursuing courses of instruction or scientific research.”

Mrs. Blackford’s $25,000 donation—about $875,836 today—funded the design, construction, and furnishing of the new building. Blackford Hall, then the tallest building on campus, was dedicated in Eugene C. Blackford’s memory on June 1, 1907 (pdf). It was one of the first residential buildings built entirely of reinforced concrete. The main floor featured a dining room, meeting hall, and serving room. The second floor served as a women’s dormitory, and the basement contained a kitchen, laundry room, storage, and servants’ quarters. The first Symposiums on Quantitative Biology were held in Blackford before moving to Bush Lecture Hall in 1953 and then to Grace Auditorium in 1986.

Much has changed within Blackford Hall since 1907. Renovations have added more dining space and a basement bar. To this day, CSHL faculty, staff, students, and visitors continue to meet there to enjoy meals and talk science.

McClintock Laboratory

Today, this CSHL landmark bears the name of 1983 Nobel laureate Barbara McClintock. But McClintock was only 12 years old when the building opened in 1914. Before she walked its halls, and until it was renamed in her honor at the 1973 Symposium, the building was called the “Animal House.”

No, not that kind of animal house. You’d find no out-of-control frat parties there. Its original purpose was to be an animal breeding facility and, according to the 1911 Carnegie Institution annual report (pdf), to “relieve the main building (Carnegie Library) of the dirt that is inseparable from [its] culture.” By McClintock’s arrival in 1941, the breeding pens had been replaced by experimental labs. It was here that two of CSHL’s eight Nobel laureates—McClintock and 1969 winner Alfred Hershey—conducted their genetics research.

Today, the brick and stucco building is home to three CSHL Cancer Center members. Assistant Professor Katherine Alexander studies nuclear speckles and their role in gene regulation. Assistant Professor Corina Amor Vegas’ anti-aging research focuses on cellular senescence—when cells stop dividing but don’t die. Associate Professor Camila dos Santos investigates how pregnancy affects breast cancer risk. Their work has added to the building’s pedigree and to the legacies of their predecessors who once walked the same halls.

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Since its inception, Cold Spring Harbor Laboratory’s DNA Learning Center (DNALC) has become a world leader in biology education.

Now, the DNALC brings its innovative hands-on science curriculum to Passaic County, NJ. The new branch is part of the Passaic County Technical Institute’s (PCTI’s) John Currie Biotechnology Innovation Center. This is the Garden State’s first DNALC. It includes state-of-the-art research and teaching laboratories for students in grades 5-12.

“We’re able to offer the same hands-on programming the DNALC has become known for—field trips, summer camps, Saturday DNA! programs, and more,” says Arie Kaz, educator and manager at the New Jersey DNALC. “Our new location increases accessibility not only for Passaic County, but also for surrounding Sussex, Morris, Essex, and Bergen counties.” That means new career-training opportunities.

PCTI is a public vocational school in Wayne, NJ, serving more than 5,000 students. The Passaic DNALC will also support PCTI’s Academy of Biotechnology program. In partnership with nearby Passaic County Community College, the program offers up to 60 course credits and an Associate’s Degree in Biotechnology upon completion.

“Our partnership with PCTI will help students gain invaluable hands-on laboratory experience and prepare them for future careers in science and the biotech industry,” Kaz says.

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Prostate cancer is a quiet killer. In most men, it’s treatable. However, in some cases, it resists all known therapies and turns extremely deadly. A new discovery at Cold Spring Harbor Laboratory (CSHL) points to a potentially groundbreaking solution. CSHL Professor Lloyd Trotman’s lab has found that the pro-oxidant supplement menadione slows prostate cancer progression in mice. The supplement is a precursor to vitamin K, commonly found in leafy greens. The story begins more than two decades ago.

In 2001, the National Cancer Institute’s SELECT trial sought to determine if an antioxidant vitamin E supplement could successfully treat or prevent prostate cancer. The trial involving 35,000 men was planned to last up to 12 years. However, after just three years, participants were told to stop taking their supplements. Not only had vitamin E failed to slow or prevent prostate cancer—more men taking the supplement started to get the disease. Seeing these results, Trotman thought, ‘If an antioxidant failed, maybe a pro-oxidant would work.’ His new findings in mice show just that.

Trotman and his team monitored prostate cancer growth in mice treated with menadione (center), mice given menadione and an antioxidant (right), and an untreated control group (left). Press play to see what happened to the cancer cells in each group.

When mice with prostate cancer are given menadione, it messes with the cancer’s survival processes. Trotman’s team has discovered that menadione kills prostate cancer cells by depleting a lipid called PI(3)P, which works like an ID tag. Without it, the cells stop recycling incoming materials and eventually explode. Trotman explains:

“It’s like a transport hub, like JFK. If everything that goes in is immediately de-identified, nobody knows where the airplanes should go next. New stuff keeps coming in, and the hub starts to swell. This ultimately leads to the cell bursting.”

This causes the cancer’s progression to slow significantly in mice. Trotman now hopes to see the experiment translated to pilot studies in human prostate cancer patients:

“Our target group would be men who get biopsies and have an early form of the disease diagnosed. We wonder if they start to take the supplement, whether we would be able to slow that disease down.”

Amazingly, Trotman’s research suggests menadione may also prove effective against myotubular myopathy, a rare condition that prevents muscle growth in infant boys. Those diagnosed rarely live beyond early childhood. Trotman’s lab has found that depleting PI(3)P with menadione can double the lifespan of mice with this condition.

If the results hold up in humans, it would mean that men with prostate cancer can enjoy a better quality of life and more time with their families. It could also mean more precious time for children born with an incurable disease.

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It’s more common in children, but when diagnosed in adults, it’s far more deadly. Rhabdomyosarcoma (RMS) is a cancer of the soft tissue—muscle, fat, tissues, tendons, nerves, or even blood vessels. We often think of it as a pediatric cancer, but that’s not the whole story. Sometimes, it strikes later in life. Such was the case with T.J. Arcati, a father of two and late founder of the Friends of T.J. Foundation.

When he founded the organization, his main focus was getting well. Someday, he’d hoped to support research into rare forms of cancer like RMS. But his first priority was being there for his wife, Heidi, and their children, Hadley and Hunter. Tragically, T.J. Arcati lost his battle just four years after his diagnosis. He was 35. Since then, the Arcati family has joined with others in the sarcoma community to ensure that scientists studying RMS get the funding they need to continue their work.

Earlier this year, Hunter and Hadley Arcati proudly presented Cold Spring Harbor Laboratory (CSHL) with a check for $50,000. Over the past decade, CSHL has led the search for new therapeutic strategies that may someday be deployed against RMS and other sarcomas. The call for action came at a 2014 Banbury Center meeting. The Friends of T.J. Foundation was one of several local groups that funded the gathering.

CSHL recently spoke with the Foundation’s CEO, T.J.’s father, Tom Arcati, about his son’s legacy. “Our hopes and dreams for finding better treatments and outcomes for sarcoma patients pale in comparison to a young person’s struggle when they are faced with an unimaginable situation only to hear about a lack of research,” Arcati says.

That is why, over the past 10 years, the Friends of T.J. Foundation has donated more than $500,000 to support the work of CSHL Professor Christopher Vakoc. This funding has yielded several significant breakthroughs, including remarkable advances in RMS and Ewing sarcoma research.

“T.J.’s love of life, family, and friends will have an everlasting impact on the community,” Arcati says. “In return, CSHL and all who knew T.J. are generously trying to solve the problem and find answers to the complex questions T.J. had. We will all continue where he left off.”

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Imagine you wake up in a hospital without a single memory of the last month. Doctors say you had a series of violent episodes and paranoid delusions. You’d become convinced you were suffering from bipolar disorder. Then, after a special test, a neurologist diagnoses you with a rare autoimmune disease called anti-NMDAR encephalitis. This is what happened to Susannah Cahalan, a New York Post reporter who would go on to write the best-selling memoir Brain on Fire: My Month of Madness.

Anti-NMDAR encephalitis can lead to hallucinations, blackouts, and psychosis, says Cold Spring Harbor Laboratory Professor Hiro Furukawa. It mostly affects women ages 25 to 35—the same age at which schizophrenia often presents itself. But what’s happening in anti-NMDAR encephalitis is something else.

Furukawa specializes in NMDARs, brain receptors that play a critical role in cognition and memory. “In anti-NMDAR encephalitis, antibodies bind to those receptors and prevent them from working,” he explains. As an autoimmune response, the brain becomes inflamed—hence, Brain on Fire.

While some treatments are available, their effectiveness varies depending on symptom severity. New research from the Furukawa lab may explain why. In a recent study, Furukawa and colleagues map how antibodies from three patients bind to NMDARs. They find that the way in which each of the three antibodies binds to NMDARs differs. The discovery marks an important step in gaining a fuller understanding of anti-NMDAR encephalitis, a condition first diagnosed in 2008. Furthermore, it suggests personalized medicine may be critical for treating this disease.

“Distinct binding patterns manifest in different functional regulation levels in NMDARs,” Furukawa explains. “This affects neuronal activities. So, different binding sites may correspond to variations in patients’ symptoms.” Uncovering those correlations could lead to more precise therapeutic strategies. Imagine, for example, that scientists identify several binding sites common among encephalitis patients. Pharmacologists could then design new drugs to target these sites. But that’s not all. Personalized medicine could also mean more accurate diagnoses, Furukawa says.

“It’s still a rare disease, but it could be misdiagnosed or underdiagnosed. Therefore, we need to spread awareness. Could, for example, some schizophrenic patients have this disease? Could it be caused by antibodies?”

Currently, it’s said that anti-NMDAR encephalitis affects one in 1.5 million people. Yet, in time, we may find it’s more common than previously assumed. That’s a scary thought. However, it could explain why existing psychiatric medicine does not work for some people diagnosed with bipolar disorder and other mental health conditions—a huge revelation for patients as well as the families and therapists who care for them.

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What if there was a tiny drone whose in-flight controls were modeled on the visual capabilities of the common fruit fly? What if individual neurons in the human brain were sensitive to speech context?

Yesterday’s flights of fancy are today’s emerging discoveries as leading scientists from around the world gather at Cold Spring Harbor Laboratory (CSHL) to discuss the journey “From Neuroscience to Artificially Intelligent Systems” (NAISys). The NAISys meeting challenges researchers at the intersection of AI and neuroscience to identify insights from brain studies that may be applied to new AI models. That intersection is a field known as NeuroAI.

“AI is making a lot of progress,” says McGill University Associate Professor Blake Richards. “But there’s a growing sense that this progress can only take us so far. Understanding the mechanisms by which animals intelligently interact with the complex world we live in is one of the best ways to stimulate new directions in AI research.”

Started in 2020, NAISys is a biennial conference held as part of CSHL’s world-renowned Meetings & Courses Program. Richards is one of three of the meeting’s co-organizers along with CSHL Professor Anthony Zador and University of California, Berkeley Professor and HHMI Investigator Doris Tsao.

This year’s meeting covered a range of topics, from incorporating AI into health care to hardware that can process data like the human brain. CSHL Professor Alexei Koulakov presented an AI that can identify odors. CSHL Assistant Professor Helen Hou’s lab introduced computer vision technology that captures mouse facial expressions at high speeds. And yes, there was a presentation on fly-minded drones as well. That one came to us from Hanyang University Assistant Professor Anmo Kim.

“NAISys brings together a unique community of researchers,” says Richards. “And I feel privileged to be a part of it.”

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On the sunny morning of September 15th, 2024, Cold Spring Harbor Laboratory (CSHL) held its 23rd Annual Women’s Partnership for Science Lecture and Luncheon at the Banbury Conference Center in Lloyd Harbor. With almost 300 attendees, the event raised over $360,000 to support women scientists’ research at CSHL. The featured speaker was CSHL’s Dr. Corina Amor Vegas and the event honored Dr. Laurie Landeau.

Laurie Landeau has been connected to CSHL for almost 40 years, first becoming a trustee in 1988, following in her father’s Ralph’s footsteps. Since its beginning, Laurie has been an avid supporter and champion of CSHL’s DNA Learning Center. The Brooklyn DNA Learning Center is proudly named the Laurie J. Landeau Campus. Most recently, Laurie and her husband Robert Maze, have committed support more broadly to CSHL’s education programs.

Laurie grew up on Long Island where her love of nature and marine life first took hold. Laurie is a veterinarian; a businesswoman; an environmentalist; a teacher; a philanthropist; and an oyster farmer. In all of these positions, Laurie has been a steadfast and dedicated advocate for science, for nature, and for science education.
At the luncheon, President and CEO of CSHL Dr. Bruce Stillman thanked her for her valiant efforts to raise funds and awareness for CSHL.

Founded in 2002, the annual event raises funds each year to help support women students, postdocs, and scientists performing cutting-edge research at CSHL with more than four million dollars raised to date.

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Imagine yourself sometime in the far future aboard a routine rocket to Mars. Someone just spilled their drink. Without gravity, it collects in floating blobs that ripple right before your eyes. Now freeze.

What you see might look something like the above image from Cold Spring Harbor Laboratory’s (CSHL’s) Cheadle lab. But those purple and green blobs aren’t the floating remains of somebody’s drink. They’re mysterious cells in the brain’s visual cortex called OPCs.

The visual cortex processes everything we see. Incoming visual information is relayed to this outer layer of the brain via synapses—the silver streaks above. When the brain’s neural circuits are first wired up, more connections, or synapses, are created than needed. As the brain accumulates new experiences and information, OPCs shape neural circuitry by pruning unnecessary synapses.

“OPCs are doing all sorts of things in the brain that help it to function in a normal, healthy way,” CSHL Assistant Professor Lucas Cheadle says. OPCs are a specialty of the Cheadle lab. He and his team discovered OPCs’ function as neural landscapers in 2022. Before that, they were thought only to produce oligodendrocytes, cells that sheath and support neurons. Now, Cheadle has developed new ways to zoom in and see OPCs in action.

“We’re able to see what thousands of OPCs, and even smaller groups of 30-50, are doing,” he explains. “From there, we can figure out which synapses are fully engulfed by an OPC, which are in the process of being pruned, and which have maybe just been checked on by an OPC but not processed.”

The new techniques used to produce the image above have become essential tools in Cheadle’s ongoing work. He and his team are now building on their 2022 discovery to help paint a complete picture of OPCs’ role in health and disease. Cheadle explains: “These mysterious cells are one of the primary sources of glioma,” a deadly brain cancer. “They’re potentially involved in Alzheimer’s disease as well.”

It’ll take more research to illustrate these connections in detail. In the meantime, Cheadle is eager to share his lab’s new tools with researchers around the world. “The brain is constantly changing, and the same approaches you’d use to look at one type of cell can’t just be applied across the board,” he says. “We’re adapting and innovating to keep up with it—to better understand how the brain works.”

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Cold Spring Harbor Laboratory (CSHL) Professor Adrian Krainer has won the Albany Prize, one of America’s largest awards for biomedical research. He now joins a prestigious list of recipients that includes names like Anthony Fauci, Emmanuelle Charpentier, and Jennifer Doudna.

The Albany Prize recognizes scientists whose work has translated from “the bench to the bedside.” It’s a long and difficult journey. Many basic bioscience breakthroughs never make it. Indeed, it took years for Krainer’s research in RNA splicing to make its way to the clinic. But when it did, the results were undeniable. His breakthroughs led to the first FDA-approved treatment for spinal muscular atrophy (SMA), the leading genetic cause of infant death. Now, Krainer is set to receive one of the most lucrative prizes in all of science and medicine.

“On behalf of Cold Spring Harbor Laboratory’s Board of Trustees, faculty, students, and staff, I congratulate Adrian Krainer on this incredible honor,” said CSHL President and CEO Bruce Stillman. “His devotion to RNA splicing research has impacted countless patients and their families. It’s a perfect example of how fundamental research can lead to life-changing discoveries.”

At $500,000, the Albany Prize is the second-most valuable prize for medicine in the United States and the fourth-most in the world. Thirteen past winners have gone on to receive the Nobel Prize. Krainer will share this year’s award with Lynne Maquat and Howard Chang.

“I feel very honored to receive the Albany Prize, and to share it with Lynne and Howard,” Krainer says. “It is very humbling to join the list of distinguished prior recipients of this award. I am grateful to the selection committee for recognizing the importance of my lab’s research on mRNA splicing, the impact of Spinraza for the treatment of SMA, and the promise of similar approaches for treating other genetic diseases and cancer.”

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What causes autism? According to the latest estimates, anywhere from 40 to 80 percent of cases may be linked to genetic risk factors. That still leaves 20 to 60 percent. Studies suggest that viral infection in pregnant women may play a role. However, many questions remain. How does this work? When is the risk greatest? Perhaps most tantalizing, why do some fetuses appear more vulnerable than others?

Today, answers are beginning to emerge. With the help of partners like the Simons Foundation, Cold Spring Harbor Laboratory (CSHL) has played a leading role in identifying autism’s genetic roots. Now, CSHL scientists are helping to explain how inflammation during pregnancy may lead to neurodevelopmental disorders in children.

Irene Sanchez Martin is a postdoc in CSHL Assistant Professor Lucas Cheadle’s lab. She recently presented her research on maternal immune activation at a Society for Neuroscience press conference in Chicago. She points to recent experiments in the Cheadle lab in which a mouse embryo may begin to show early signs of developmental deficits soon after its pregnant mother is exposed to a virus.

“The model we use is very well established for autism spectrum disorder,” Sanchez Martin explains. “The difference in my work is that I check what happened to the fetuses 24 hours after exposure to maternal inflammation, rather than analyzing the behaviors of the offspring as adults.” This is the first time scientists have been able to look at the effects of prenatal inflammation on an embryo in an autism model. Such research may one day enable physicians to identify early warning signs before a child is even born.

Before they can get there, Sanchez Martin will need to complete her research. She’s just two years into her postdoctoral studies at CSHL. However, her work is already producing exciting results. For example, in the experiments she discussed, while all female embryos appear to be protected from developmental deficits, as many as one-third of the males are strongly affected.

This finding tracks with the long-held understanding that autism is more common in boys than girls. Is the connection correlative or causal? There’s yet another question that will need answering. What’s important is that each opens up new avenues of research. And that means new opportunities to help improve the lives of expecting mothers as well as children with autism and their families.

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Tending a garden is hard work. Imagine it from the plants’ perspective. Each relies on fine-tuned genetic processes to pass down accurate copies of chromosomes to future generations. These processes sometimes involve billions of moving parts. Even the tiniest disruption can have a cascading effect. So, for plants like Arabidopsis thaliana, it’s good to have a backup plan.

“Chromosomes have to be accurately partitioned every time a cell divides,” explains Cold Spring Harbor Laboratory (CSHL) Professor and HHMI Investigator Rob Martienssen. “For that to happen, each chromosome has a centromere. In plants, centromeres control chromosome partitioning with the help of a molecule called DDM1.”

Martienssen discovered DDM1 in 1993 with a team that included Tetsuji Kakutani, then a postdoc with CSHL Fellow Eric Richards. Kakutani and Martienssen recently reunited to investigate a question 30 years in the making. When humans lose their version of DDM1, centromeres can’t divide evenly. This causes a severe genetic condition called ICF syndrome. But if the molecule is so important, why isn’t Arabidopsis affected when DDM1 is lost? Martienssen explains:

“We wondered why it would be so different. About 10 years later, we found that in yeast, centromere function is controlled by small RNAs. That process is called RNAi. Plants actually have both DDM1 and RNAi. So, we thought, ‘Let’s isolate these two in Arabidopsis to see what happens.’ We did that, and sure enough, the plants looked really horrible.”

When the team looked closer, they found that a single transposon inside chromosome 5 was responsible for the defects. Transposons move around the genome, switching genes on and off. In Arabidopsis, they trigger DDM1 or RNAi to help centromeres divide. But when DDM1 and RNAi are missing, the process is disrupted.

“We found very few copies of this transposon anywhere else in the genome,” Martienssen says. “But the centromere of chromosome 5 was infested with these things. We thought, ‘Wow, OK, this really might be it.’ Then we started working on how to restore healthy function.”

Martienssen and the study’s lead author, Atsushi Shimada, developed molecules called short hairpin RNAs that target the transposons. Martienssen explains:

“Those small RNAs make up for the loss of DDM1. They recognized every copy of the transposon in the centromere and, amazingly, restored centromere function. So now the plants were fertile again. They make seeds. They look much better.”

Of course, it’s not all about plants. In humans, uneven centromere division has been linked to conditions like ICF and early cancer progression. Martienssen hopes his team’s work may one day point to better treatments for these and other diseases.

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When OpenAI released ChatGPT in November 2022, artificial intelligence quickly hit the mainstream and became a global cultural phenomenon. The chatbot dominated headlines as it authored news articles, passed the bar exam, drafted lesson plans for teachers, and even wrote code. ChatGPT became the fastest-growing consumer application ever.

In the months following its launch, companies scrambled to create competing large language models. This started what many consider an AI “arms race.” Now, the technology is everywhere you look. Yet, artificial intelligence is much bigger than ChatGPT and the other generative AI systems that have taken the world by storm. Models that use AI have been working behind the scenes for years in fields ranging from cybersecurity to science and medicine.

At Cold Spring Harbor Laboratory (CSHL), researchers work to unlock AI’s full potential by combining AI and neuroscience. They hope one day smarter models will lead to advancements that benefit everyone, not just the lucky few.

What is AI? And what isn’t it?

Artificial intelligence, or AI, is a scientific field that uses computers to solve problems that typically require human intelligence. Large language models like ChatGPT are trained on vast amounts of data scraped from all corners of the internet, including Web pages, digitized books, Wikipedia articles, and posts on public forums like Reddit.

These chatbots use “neural networks,” or algorithms inspired by how the brain works, to process new data and detect patterns without human input. “Most of modern AI is actually an outgrowth of neuroscience,” argues CSHL Professor Anthony Zador.

CSHL NeuroAI Scholar Kyle Daruwalla talks about making AI more energy-efficient and accessible for all.

Because large language models have access to such massive amounts of information, they can learn and act in ways that meet and sometimes even surpass our own abilities.

“We do have chatbots right now that have very convincing and realistic conversations with humans,” says Kyle Daruwalla, a NeuroAI scholar at CSHL. “But it’s skin deep,” he adds. “There’s no depth behind the words that are said.”

In other words, AI models do not have independent thoughts or feelings and do not truly understand meaning. However, they are extremely good at pretending they do. Some are so good, they’ve persuaded users they’re actually sentient. So, how will we know if one ever does possess human levels of intelligence? And will this happen anytime soon?

Move over, Turing

In 1950, mathematician Alan Turing developed a test to determine whether computers could behave intelligently. He proposed a scenario in which a human judge would converse with both an AI model and another human. If the judge could not tell the difference between the two, that meant the model possessed human-like intelligence. Turing didn’t specify many details about how the test would be carried out. So, scientists disagree over whether or not certain AI chatbots have passed. Many disagree with the test entirely. They say it doesn’t truly indicate an AI model’s ability to “think.” Additionally, the test assumes that language represents peak human intelligence, Zador and his colleagues say.

“It doesn’t account for our abilities to interact with and reason about the physical world,” Zador says. So, he and his colleagues have called for a new “embodied” Turing test grounded in principles of NeuroAI, a field at the intersection of neuroscience and AI. “NeuroAI is based on the idea that a better understanding of the brain will reveal the ingredients of intelligence and eventually lead to human-level AI,” Zador explains.

The new test would pit AI animal models against their real-world counterparts, assessing how well each interacts with its environment. The test shifts focus away from AI models that play games and use language, which are capabilities that are especially well-developed in or unique to humans. Instead, it assesses abilities shared by all animals, including sensorimotor skills and interactions with unpredictable environments.

Think about walking down a crowded city sidewalk. AI isn’t there yet. In fact, it isn’t able to walk at all. The robots you may have seen running through obstacle courses? They’re programmed to do that. They don’t learn it. Therefore, they aren’t AI.

Building systems that can pass the embodied Turing test could accelerate the next generation of AI, according to Zador. Yet, to reach this next generation, Zador and his colleagues believe we must bridge the gap between neuroscience and AI. Many of the cutting-edge AI systems we use today were inspired by old neuroscience from the 1950s and ‘60s. Though scientists have made more recent breakthroughs, these advancements have yet to translate over to AI.

To combine these two fields, resources will need to be allocated into three main areas: training researchers equally in neuroscience and AI, creating an open and shared platform to build and test AI systems, and investing in fundamental research that will allow us to define the ingredients of intelligence.

Using AI to map the mind

Not only can neuroscience help us build better AI, but AI may help us better understand neuroscience, too. CSHL Professor Partha Mitra uses AI to uncover more about our brain circuitry.

“We want to understand how we think, how we feel,” Mitra says. “These are philosophical questions that have been around for thousands of years. And we have made significant progress in the 20th century, but we still lack essential data sets.”

In the old days, studying neural circuits required scientists to look carefully at sections of the brain under a microscope. Yet, as technology improved and computers became able to store much more data, this method became obsolete. Scientists now believe the human brain has around 100 billion neurons, each of which talks with a thousand other neurons.

“The data from just one human brain at a light microscopic scale is about a petabyte, which is very large,” Mitra says. “To study that, we need assistance from the computer. We are trying to automate the analysis of brain circuitry from microscopic images so that we can ultimately reach our goal of understanding how these circuits work.”

Mitra and his colleagues have developed a method of tracing neurons and their connections more efficiently, using a combination of machine-learning techniques and a form of mathematics called topological data analysis. Topological data analysis looks at the specific shape of data in a way that emphasizes connectivity. This method allows the Mitra lab to teach algorithms to detect specific nerve cells and fibers more accurately without as much human oversight.

Not only could knowing how our brain circuitry works lead to better AI models. It could have psychiatric applications, too. Eventually, we may be able to pinpoint differences in the brain circuits of people living with neurological disorders or mental health conditions.

“If you don’t know what’s different, one can’t really start addressing it,” Mitra says. “And you may or may not want to address that difference.”

To ensure their findings will have a broad impact on society, the researchers are making their code available for others to use on their own data.

AI in the future

Artificial intelligence has revolutionized the speed and way in which we process data. Yet, like any emerging technology, AI has sparked widespread fears over how it could be used in the future. Some of these fears are warranted, especially those over the spread of disinformation and job loss, Zador says. However, the hype over AI becoming self-aware isn’t a pressing fear—at least not yet.

Daruwalla views AI in the same light as the internet. It will certainly make dramatic changes in our lives and exacerbate existing problems, but it should ultimately be a force for good.

CSHL Assistant Professor Peter Koo is training AI to search the genome for potential breast cancer risk factors.

In fact, a better understanding of the brain could be just the beginning. Right now, there are CSHL scientists using AI to analyze cancer and other diseases. Their findings could help inspire lab experiments that point to new drug targets and therapeutic strategies.

“I think the best use of it is for scientific research, for drug discovery,” Daruwalla says. “The output of that is objectively going to make all of our lives better.”

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“Those vibrant flowers have been a wonderful addition to the Laboratory’s landscape,” says RK Narayanan, Senior Director at CSHL’s Office of Business Development & Technology Transfer. “I’ve always found that area to be particularly peaceful. And the flowers have enhanced its inherent beauty.”

CSHL completed restoration work on its 174-year-old seawall in 2022. Once the construction crews were gone, it was time to spruce the place back up. Prior to the renovation, the area had been nothing but green. CSHL’s on-staff horticulturalists saw an opportunity to add a little more color.

“These flowers are all Northeast natives,” CSHL Horticulturalist Agnes P. Cwalina says. “They’re attracting native species of bees. Birds are stopping by on migration to eat the seeds. If plants aren’t being eaten by birds, bugs, or bees, there’s something wrong. That means the plant isn’t good for what lives around us. The beautiful thing also is that these are perennials. They’ll be coming back year after year.”

Since 1890, CSHL and its predecessors have been stewards of the local environment. This responsibility goes beyond mere preservation work. CSHL’s dedicated grounds crew and horticulturalists labor year-round to ensure the area’s health and beauty lasts beyond the current season.

“Right plant, right place is the biggest thing,” CSHL Horticulturalist Riley McKenna says. “It’s easier to work with nature than against nature. Native species, like the flowers by the seawall, are just better. They’re more drought tolerant. They’ve adapted to the area. Cold Spring Habor has a maritime climate. There’s a lot of moisture and salt. But because we have the water, there’s also so much biodiversity. We’re very lucky to see all this every day.”

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Metastatic cancer can be a devastating diagnosis. The cancer is spreading. It may travel to multiple organs in the body. This could mean more pain and ultimately, death.

Unfortunately, just how cancer spreads remains unclear. But now, Cold Spring Harbor Laboratory (CSHL) Professor Adam Siepel and colleagues have a way to better understand that process. New technology developed at Weill Cornell Medicine barcodes cells to track the highways by which prostate cancer spreads throughout the body.

The resulting roadmap shows that most cancer cells actually stay put within the tumor. However, it also reveals that a small number of aggressive cells seed cancer’s rare migrations from the prostate to the bones, liver, lungs, and lymph nodes.

The discovery was made in collaboration with Dawid Nowak’s laboratory at Weill Cornell Medicine. It involved using a new mouse model called Evolution in Cancer Prostate (EvoCaP) along with an analysis pipeline known as Evolutionary Lineage Tracing in R (EvoTraceR). This allowed scientists to use short sequences of DNA that act as genetic barcodes to trace the movement of individual cancer cells.

The new technology offers a big step up from previous methods, says Siepel. In the past, researchers might have used a combination of imaging techniques and whole-genome sequencing. But that meant more time and money. Plus, it didn’t necessarily ensure more accurate readings. On the other hand, Siepel says:

“This barcoding lets us read off the precise tracing information about how the cancer has spread from its origin to the tissues to which it’s metastasized.”

The readout provides researchers with a clearer picture of how cancer spreads. And that newfound clarity could set the stage for further advances. CSHL postdoc Armin Scheben explains:

“We’ve laid the fundamental molecular biology foundation for a whole lot of other questions to be answered. This is the beginning phase of a much larger project where our colleagues are expanding this work to other types of cancer, and we start looking at therapeutic interventions for metastasis.”

If they’re successful, it could lead to new, more targeted therapeutics. There’s a long road ahead, but one day, mapping cancer’s spread could mean stopping it in its tracks.

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Our immune system spans two worlds—innate and adaptive. Innate immune cells are like troops at the gate ready to hold off invaders and raise the body’s alarms. Adaptive immune cells are specialists that take longer to respond but can fight off foes in a more targeted manner. Curiously, there are also immune cells that exist between worlds. Important among these cellular combatants are innate-like T cells. Their hybrid-like nature makes them promising candidates for developing new kinds of immunotherapies against diseases such as cancer.

The problem is that scientists still don’t know much about how this unique type of T cell functions and develops in humans. Cold Spring Harbor Laboratory (CSHL) Assistant Professor Hannah Meyer and her collaborator at the University of Colorado Anschutz, Professor Laurent Gapin, set out to determine just that.

“Studying the development of the immune system is as important as investigating its role in disease,” says Salomé Carcy, a former graduate student in the Meyer lab who co-led this study. “We need to understand immune cells’ origin to gain insights into their functional potential in pathological contexts. One of the key motivations of our work was to investigate how much our knowledge built on mouse models applies to human physiology.”

The team discovered that innate-like T cells mature differently in humans than in mice, and that age plays a critical role here. They found that early in life, most innate-like T cells in the human thymus aren’t able to use all of their immune abilities. It’s as if they have one hand tied behind their back. In adults’ bloodstreams, however, it’s a different story. There, innate-like T cells are on standby, ready to fight as soon as they receive their ‘go’ signal. This pattern is observed in both mice and humans.

According to Meyer, these distinctions should make for key considerations when it comes to developing and testing immunotherapeutics, especially since much preclinical trial research is conducted in mouse models. She says:

“We need to take these differences into account. We’d be interested to look at these differences to see how they change over time and if these cells are more powerful at different ages. And is this something we can therapeutically exploit?”

For now, Meyer and her team continue to dissect the complicated lives of immune system agents such as innate-like T cells. Their work may one day allow researchers to harness the power of both the innate and adaptive immune systems into a new, more formidable kind of immunotherapy.

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Cold Spring Harbor Laboratory (CSHL) School of Biological Sciences (SBS) graduate Shushan Toneyan has won the 2024 International Birnstiel Award for Doctoral Research in Molecular Life Sciences. A member of the SBS Class of 2024, Toneyan is one of six recipients of this year’s award. She received it in recognition of her thesis research in CSHL Assistant Professor Peter Koo’s lab.

“I feel incredibly lucky to have been part of the Koo lab and the CSHL graduate program,” Toneyan says. “I am sincerely grateful to Peter, my thesis committee members, and my lab mates for the many years of encouragement and rigorous scientific discussions. And I thank the SBS for their warm support and nomination.”

Toneyan’s doctoral work culminated in the launch of CREME, a new AI-powered virtual laboratory. With the push of a button, CREME can perform thousands of experiments to study key areas of the genome. It may one day help scientists find new therapeutic targets for genetic diseases.

“I am thrilled to congratulate Shushan on receiving this well-deserved award,” Koo says. “Her pioneering research has advanced the application of artificial intelligence in genomics. I am excited to see how her future work continues to shape our understanding of life sciences and drive innovation in healthcare.”

The International Birnstiel Award was established in 2019. It is awarded each year by the Max Birnstiel Foundation and the Research Institute of Molecular Pathology. Award winners receive a trophy, certificate, and €2,000 prize.

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Imagine you’re looking at millions upon millions of mysterious genetic mutations. With CRISPR gene-editing technology, a select few of these mutations might have therapeutic potential. However, proving it would mean many thousands of hours of lab work. Just figuring out which ones are worth exploring further would take a lot of time and money. But what if you could do it in the virtual realm with artificial intelligence?

CREME is a new AI-powered virtual laboratory invented by Cold Spring Harbor Laboratory (CSHL) Assistant Professor Peter Koo and his team. It allows geneticists to run thousands of virtual experiments with the click of a button. Now, scientists can use it to begin identifying and understanding key regions of the genome.

The program is modeled after CRISPR interference (CRISPRi), a genetic perturbation technique based on CRISPR. CRISPRi allows biologists to turn down the activity of specific genes in a cell. CREME lets scientists make similar changes in the virtual genome and predicts their effects on gene activity. In other words, it’s almost like an AI version of CRISPRi. Koo explains:

“In reality, CRISPRi is incredibly challenging to perform in the laboratory. And you’re limited by the number of perturbations and the scale. But since we’re doing all our perturbations [virtually], we can push the boundaries. And the scale of experiments that we performed is unprecedented—hundreds of thousands of perturbation experiments.”

Koo and his team tested CREME on another AI-powered genome analysis tool called Enformer. They wanted to know how Enformer’s algorithm makes predictions about the genome. Questions like that are central to Koo’s work, he says.

“We have these big, powerful models. They’re quite compelling at taking DNA sequences and predicting gene expression. But we don’t really have any good ways of trying to understand what these models are learning. Presumably, they’re making accurate predictions because they’ve learned a lot of the rules about gene regulation, but we don’t actually know what their predictions are based off of.”

With CREME, Koo’s team uncovered a series of genetic rules that Enformer learned while analyzing the genome. That insight may one day prove invaluable for drug discovery. “Understanding the rules of gene regulation gives you more options for tuning gene expression levels in precise and predictable ways,” says Koo.

With further fine-tuning, CREME may soon set geneticists on the path to discovering new therapeutic targets. Perhaps most impactfully, it may even give scientists who do not have access to a real laboratory the power to make these breakthroughs.

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On September 10, Cold Spring Harbor Laboratory (CSHL) proudly celebrated the centennial anniversary of the CSHL Association Board at a wine and cheese reception held on the Beckman Laboratory patio. The current Association Board, including Association President Mark Hamer, several Past Presidents and Honorary Association Directors, joined CSHL Trustee and Board Chair Marilyn Simons, Dr. Bruce Stillman and many of CSHL’s scientists to mark this very special occasion.

Originally named the Long Island Biological Association, the CSHL Association was formed in 1924 when a group of prominent local citizens banded together to save the Laboratory, which was experiencing financial stress. They succeeded in raising the necessary funds to continue the Lab’s operation and assumed responsibility for the fledgling research institution. Counting Louis Comfort Tiffany, JP Morgan, Marshall Field III, and Cornelius Vanderbilt among its inaugural members, this Board’s unparalleled support has continued and grown over the decades. Today’s Association Directors carry forward this remarkable legacy of guidance, ambassadorship, and support of Cold Spring Harbor Laboratory.

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The Robert D.L. Gardiner Foundation has made a $3 million commitment to Cold Spring Harbor Laboratory (CSHL), establishing an endowment to name the Robert David Lion Gardiner Chair of Library & Archives. This endowment will support CSHL’s Library & Archives and the Center for Humanities’ broad educational programs in perpetuity. This gift will ensure that the mission of CSHL’s Library & Archives—to promote the appreciation of Suffolk County and the history of science and technology on Long Island—will continue for generations to come. Ludmila Pollock, CSHL’s executive director of Library & Archives, will be the inaugural Robert D.L. Gardiner Chair.

Founded in 1890, CSHL has made significant contributions to Long Island’s social, economic, and environmental history. With a focus on chronicling the history of molecular biology through the collections of prominent scientists, CSHL’s Library & Archives has acquired, preserved, and cataloged the personal collections of dozens of eminent scientists (including six Nobel laureates), and is home to a unique and valuable collection of books, journals, and online materials. The Library is available to historians, scholars, scientists, artists, and the public. In addition, the Archives hosts special meetings for Nobel laureates and other key contributors to scientific discoveries that shape our lives.

As part of its mission to cultivate and promote interest in Long Island’s societal heritage, the Robert D.L. Gardiner Foundation sponsors institutions that inform the general public of the region’s historic contributions that have made and continue to make the world a better place. Inspired by these connections, CSHL is thrilled to partner with the Robert D.L. Gardiner Foundation to highlight historical links between scientific research, technological innovation, economic development, and life on Long Island.

Bruce Stillman, president and CEO of CSHL, said, “We are pleased and grateful to receive this prestigious recognition from the Robert David Lion Gardiner Foundation for the important work that CSHL’s Library & Archives does to educate students and the public and to preserve the rich history of science on Long Island.”

The inaugural Gardiner Chair Ludmila Pollock has directed CSHL’s Library & Archives since 1999. During her tenure, the department has acquired, preserved, and cataloged the personal collections of dozens of eminent scientists (including six Nobel Laureates), built a modern archival storage vault and reading room, and begun construction on an even larger state-of-the-art archives center. In 2017, Pollock established the CSHL Center for Humanities & History of Modern Biology, which awards fellowships to visiting researchers and artists and organizes public events that promote wider understanding of biological research and its history.

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Several faculty members received mainstream media attention in 2024. Professor and Director of Education Zachary Lippman was featured in The New York Times and on CNN for his team’s discovery of the gene behind plant prickles. Assistant Professor Corina Amor Vegas was featured in WIRED and on the BBC for her work demonstrating that CAR T cells can be reprogrammed to counter the effects of aging in mice.

Other faculty members contributed to national news stories as outside sources. Professor David Tuveson and Associate Professor Jessica Tollkuhn were quoted in articles from The Washington Post (see “‘Unusual’ cancers emerged after the pandemic” and “Some mice have a cheating heart”). Assistant Professor Benjamin Cowley appeared on NPR’s All Things Considered podcast.

The post Making headlines appeared first on Cold Spring Harbor Laboratory.

This October, supporting breast cancer research is as easy as buying paint. Throughout the month, for every gallon of any color premium paint sold at Aboff’s Paint stores and online at aboffs.com, the company will generously donate a portion of the proceeds to support breast cancer research at Cold Spring Harbor Laboratory (CSHL).

The original Aboff’s Paints Breast Cancer Awareness Campaign raised over $10,000 for CSHL breast cancer research in 2012. In 2023, the two Long Island institutions renewed their partnership and raised over $40,000.

“Breast cancer awareness is near and dear to all of us here at Aboff’s,” said Aboff’s Paints owner and CSHL Corporate Advisory Board member Matthew Aboff. “We are delighted to renew our partnership with Cold Spring Harbor Laboratory for October 2024 and hope to make this year’s campaign our most successful yet.”

Family-owned and operated, Aboff’s Paints has been proudly serving Long Island and the New York region for 95 years. The knowledgeable team of paint experts leverages decades of experience, and with 32 convenient locations across Long Island, they’re on hand to accommodate any residential, commercial, or industrial painting project.

For more information, contact Shayna Bowles at Aboff’s Paints ([email protected]; 631-427-2008 ext. 153) or Sarah Kitt at CSHL ([email protected]; 516-367-6808).

The post CSHL & Aboff’s Paints announce Paint & Donate campaign appeared first on Cold Spring Harbor Laboratory.

CITY OF SCIENCE: KATALIN KARIKÓ IN CONVERSATION WITH CARL ZIMMER
Friday, November 15, 2024
6:30pm
Elebash Recital Hall, CUNY Graduate Center

Hungarian-born biochemist Katalin Karikó was celebrated in the media after winning a 2023 Nobel Prize for her contributions to mRNA technology and vaccines against COVID-19. Her research has fundamentally changed our understanding of how mRNA interacts with our immune system, contributing to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times. Karikó is a professor at Szeged University in Hungary and an adjunct professor at Perelman School of Medicine at the University of Pennsylvania. She speaks about her lifesaving work with Carl Zimmer, columnist for The New York Times and author of many books about science, including the forthcoming Air-Borne: The Hidden History of the Life We Breathe.

Presented in partnership with CUNY Graduate Center and Center for Humanities and Modern Biology, BGI Nobel Laureate Archives Program
Open to the Public at no cost, reservations required

Reservations for In-Person Event

Reservations for Livestream

Presented with Cold Spring Harbor Laboratory Center for Humanities and Modern Biology, BGI Nobel Laureate Archives Program.

A video of this event will be posted a few days later on CUNY’s YouTube Channel.

Please contact Jimmy Cok at [email protected] in advance for CART services or any additional accessibility requests or concerns for in-person events.​ This event will be livestreamed, and closed captions will be provided.

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