How does learning change the wiring of your brain? How does a shark’s eye make sense of its underwater world? How does a single-celled parasite cross the barrier that protects the brain? What might neurodegeneration look like at ultra-magnified scale?
The University of Vermont will serve as the national coordinating hub for a new, $19 million, five-year National Science Foundation project that will design and build an observatory to allow researchers to investigate these questions, and others, by revealing some of life’s smallest structures in three dimensions.
The goal is to make imaging capabilities now concentrated in a handful of specialized laboratories accessible to many scientists across the country—and from many fields of biology, medicine, and the life sciences.
Led by neuroscientist Davi Bock , of UVM’s Robert Larner, M.D. College of Medicine , with co-principal investigators Doug Taatjes, director of UVM’s Microscopy Imagine Center, and Mark Ellisman at the University of California San Diego, the National Connectomics and Ultrastructure Volume Observatory (NCUVO) will bring together advanced electron microscopy, artificial intelligence, and powerful computing networks.
Coordinated from UVM, the effort will integrate state-of-the-art high-throughput electron microscopy at the university's Larner College of Medicine, with expertise in sample preparation and complementary advanced microscopy techniques at UC San Diego’s National Center for Microscopy and Imaging Research, and data management and processing at the San Diego Supercomputer Center. Together, these partners will design a system that connects biological samples to usable scientific data for researchers nationwide.
“This exciting project exemplifies UVM’s commitment to studying what matters: values-driven, innovative research that can change the world for the better,” said UVM President Marlene Tromp. “The work of this observatory will help answer vital questions about the natural world, with discoveries that can help us better understand all life on this planet. This is transformative research that UVM is proud to lead on a national level.”
For two decades, Bock has helped develop the science of “connectomics”: mapping the wiring of brains and nervous systems down to individual neurons and the synapses connecting them. His laboratory acquired the electron microscopy images that an international collaboration used to produce the first wiring map of an adult fruit fly’s entire brain— a scientific landmark reported in Nature in 2024 .
That work required enormous gains in imaging speed and computing power. While electron microscopes can reveal extraordinarily small structures, the challenge for next generation neuroscience has been assembling and aligning enough images to follow the branching paths of neurons through substantial volumes of tissue—and turning those millions of images into useful maps. Having accomplished that, the opportunity now is to expand that capacity both in terms of what problems it can be used to address, and to expand the number of scientists with access to it.
“We built a searchlight to look at one type of problem, and now, with a purpose-built facility for advanced work like this, we will use it to look at many, many different problems,” Bock says. “This new national center will be globally unique in pointing high throughput volume microscopes at the full spectrum of biology. Right now, that doesn't exist anywhere else.”
Much of the field’s effort now focuses on mapping ever-larger brains – including the whole brains of many “model species” used in scientific research. Bock wants to extend that capacity beyond whole-brain connectomics to other neurobiological systems, other species, and emerging scientific questions in how “ultrastructure” — the fine details within and between cells – enables and supports biological information processing. High throughput processing allows the collection of many more samples, and comparing multiple samples can reveal how structures differ with learning, development, or disease. Looking beyond nervous systems could illuminate the machinery inside individual cells, including one-celled creatures called protists.
Just as an astronomical observatory gives many scientists a shared way to investigate the universe, the NCUVO observatory will help researchers explore biological structures too small to see with ordinary light microscopes.
“It’s a new combination and application of technology at scale,” says Bock, an associate professor of neurological sciences at UVM’s Larner College of Medicine. "There is so much about the natural world that we don't fully understand, but to unlock those secrets research efforts must occur at a much greater scale. That's what the new observatory will do."
“The National Science Foundation’s support for this project is an investment in the essential work of discovery, and we are tremendously grateful for its confidence in UVM and our partners,” said Kirk Dombrowski, UVM’s Vice President for Research and Economic Development. “The history of science shows that transformative advances often begin with basic research: careful, curiosity-driven efforts to understand how the world works. This observatory will enable scientists to see biology in ways that were previously out of reach and pursue questions that may shape entire fields in the decades ahead.”
The team will design and test a complete path from biological samples to images that researchers can explore and analyze. Tissue preserved in resin will be cut into thousands of ultrathin slices and a state-of-the art, high-throughput electron microscope, housed in UVM’s Firestone Medical Research Building at the Larner College of Medicine, will capture their details. Then powerful computers at the San Diego Supercomputing Center will assemble the images into three-dimensional volumes.
AI will help identify cell boundaries, trace neurons, and distinguish structures within cells. Researchers will have tools to check those reconstructions, label features, and investigate their scientific questions.
At UC San Diego’s National Center for Microscopy and Imaging Research, follow-up work on selected areas can be imaged at higher resolution to connect tiny details with the larger surroundings uncovered in Vermont. Directed by world-renowned brain imaging expert Mark Ellisman, the San Diego center brings decades of experience developing sample preparation methods, advanced imaging instruments and computational tools for biological microscopy. When combined with NCUVO, the volume, capacity, and scale of connectomics work now centered in San Diego will grow significantly.
“The NCUVO design is about transforming the latest sample preparation, multimodal imaging, and computational technologies into a shared national capability rather than a specialty only available to a few,” said Mark Ellisman, the project’s co-principal investigator at UC San Diego. “At NCMIR, we will help to provide the means to turn raw microscopy image data into something that can be interpreted to advance our understanding of biological processes. By combining these capabilities with UVM’s imaging and SDSC’s resources for advanced cyberinfrastructure, we can empower scientists around the country to complete studies that compare many samples at different levels of detail, from tissues down to synapses.”
The work will generate datasets measured in petabytes—millions of gigabytes. UVM’s Vermont Advanced Computing Center will support storage and computing. Ilkay Altintas, chief data science officer at the San Diego Supercomputer Center and principal investigator of the NSF-funded National Data Platform, will guide the project’s data curation efforts. Her team will bring expertise in organizing, processing and sharing large scientific datasets, connecting the observatory’s images with NSF-supported national computing resources.
“You can’t just drop a petabyte of data on someone and say mission accomplished,” Bock says. “You have to give them tools to analyze the data.”
Four pilot projects will test how well the observatory will handle different organisms, sample sizes, and scientific needs.
One will examine how connections in the mouse hippocampus, a brain region important for memory, change following learning. Working with Anton Maximov’s laboratory at Scripps Research in California and Mark Ellisman’s team at UC San Diego, researchers will trace circuits involving neurons marked as active during a learning task.
Another will compare retinal circuitry across species to investigate how visual systems suit different environments. Bock points to sharks navigating murky versus clear water as an example of the questions such comparisons could address. The work brings together David Berson’s laboratory at Brown University in Rhode Island and Tom Baden’s laboratory at the University of Sussex in the United Kingdom, combining their expertise in retinal circuitry and the evolution of vision.
A third brings together UVM parasitologist Bruno Martorelli Di Genova’s laboratory and Christopher Moore’s laboratory at Brown University to study how the parasite Toxoplasma gondii crosses the blood-brain barrier to cause toxoplasmosis, a parasitic disease spread through contaminated food and cat litter.
"This is an amazing organism because it causes rodents to lose their fear of cat urine,” explains Bock. “It changes the behavior of cat prey to be less frightened of cats. And there's some evidence that infected humans also are less risk averse."
The fourth will examine protists—single-celled organisms with elaborate internal structures—with Omaya Dudin’s laboratory at the University of Geneva in Switzerland and Gautam Dey’s laboratory at the European Molecular Biology Laboratory in Heidelberg, Germany. Dudin and Dey received the 2026 EMBO Gold Medal for their work in evolutionary cell biology.
These are investigations in basic biology. Their purpose is to understand how living systems work, creating knowledge that could eventually inform medicine or new approaches to artificial intelligence. The work begins with curiosity-driven questions. This said, Bock and colleagues expect that this type of pipeline could also directly lead to a better understanding of the structural changes accompanying neurodegenerative diseases as well as intrinsic and therapy-initiated repair.
“Medical care depends on an understanding of the fundamental biology of normal and pathological tissue,” said Richard L. Page, M.D., dean of the Larner College of Medicine and chief medical affairs officer at UVM. "As a result of this transformational award, Dr. Bock and colleagues will provide deeper understanding of basic structure and biology, allowing for insights and therapies that have not yet been imagined."
Education is also part of the new observatory project. UVM neuroscience assistant professor Molly Stanley will coordinate work with Connectomes for Undergraduate Neuroscience Education and Learning (CUNEL), whose leadership includes Andrew Bellemer at Appalachian State University in North Carolina, Kenneth Colodner at Mount Holyoke College in Massachusetts, and Divya Sitaraman at California State University, East Bay. Together, they will develop undergraduate teaching materials using pilot data. The project also plans high-school virtual-reality materials with the VR platform syGlass and training opportunities for UVM biomedical engineering master’s students.
The five-year effort will produce a tested design, pilot datasets and an implementation plan for a future national observatory. By testing how imaging, AI and large-scale computing work together across institutions, the team will lay the groundwork to serve the broader nationwide research community in a subsequent implementation phase.
Approximately $15.68 million will directly support Bock’s work at UVM and $3.32 million will fund UC San Diego’s contributions, including the supercomputer center.
"You can't predict what we’ll find. And that's the point. Our country has historically invested in basic research for this reason, the unpredicted discoveries," Bock says. "When Van Leeuwenhoek first looked through the first microscope, he saw all these moving things,” Bock says. “It didn't change a farmer's life that day, but it led to the germ theory of disease."
That’s why Bock wants the new observatory to point its lens at all of biology. “Anything that you can think of, any tissue, any species, any organism we can look at, we should,” Bock says. “That's democratization, broadening the spectrum of questions that can be asked and answered by our national research community."