Researchers at the University of California San Diego have received new research funding from the U.S. National Science Foundation (NSF) to design and build an observatory that will allow researchers to reveal some of life’s smallest structures in three dimensions, which will empower new discoveries in neuroscience and the basic biology of life.
The new initiative will establish a National Connectomics and Ultrastructure Volume Observatory (NCUVO), the goal of which is to make imaging capabilities — now concentrated in a handful of specialized laboratories — accessible to scientists across the country studying biology, medicine and the life sciences. The project will integrate advanced high-performance electron microscopy, artificial intelligence, advanced computing and powerful data networks to create a system that converts biological samples to usable scientific data, enabling researchers to study biological systems at larger scales and with greater completeness.
The five-year, $19 million facility construction project will be led and coordinated by neuroscientist Davi Bock, PhD, at the University of Vermont (UVM), with UC San Diego Distinguished Professor of Neurosciences and Bioengineering Mark Ellisman, PhD, serving as co-principal investigator alongside Doug Taatjes, PhD, director of UVM’s Microscopy Imaging Center. Approximately $15.68 million of the new funding will directly support procurement of advanced tools and new staff recruitment for the project at UVM and $3.32 million will fund the utilization of shared advanced imaging and high-performance computing resources at UC San Diego.
Coordinated from UVM’s Larner College of Medicine, the effort will establish and integrate state-of-the-art high-throughput electron microscopy at UVM, expertise in sample preparation and complementary advanced microscopy techniques at UC San Diego’s National Center for Microscopy and Imaging Research (NCMIR), and data management and processing in conjunction with the San Diego Supercomputer Center (SDSC) at the Halıcıoğlu School of Data Science and Computing.
“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 Ellisman, who directs the NCMIR. “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 new imaging instruments 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.”
In addition to establishing the infrastructure for this next generation of imaging, the project will generate millions of gigabytes of data. Ilkay Altintas, PhD, chief data science officer at the SDSC 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.
“We're excited to help shape this important research infrastructure, which will make advanced biological imaging more accessible and open new windows into how living systems process information,” said Altintas. “Drawing on the expertise of the SDSC and the capabilities of the National Data Platform, UC San Diego will help the imaging community design and validate scalable, reproducible workflows that connect imaging data with the computing power needed to turn these remarkable images into new discoveries.”
Once the observatory is established, four pilot projects will test how well it will handle research using different organisms, sample sizes and scientific needs:
One project being used to shape the construction of the new observatory will examine how connections in the mouse hippocampus, a brain region important for memory, change following learning. Working with Ellisman’s team at UC San Diego and Anton Maximov’s laboratory at The Scripps Research Institute, scientists will trace circuits involving neurons and their synapses marked as active in establishing a new memory.
Another pilot project 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 third and fourth projects will focus on single-celled organisms, including one 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.
The five-year effort will culminate in a tested design, pilot datasets and an implementation plan for operation of the infrastructure as a facility for the nation – a true national observatory. Education is also a key part of the project, with undergraduate teaching materials and training opportunities planned around the pilot data to ensure that these new scientific resources are not just available, but that scientists know how to use them.
“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,” said Bock. “That's what the new observatory will do."
While these pilot projects will produce more fundamental breakthroughs in biology, these discoveries also have the potential to reshape our understanding of neurodegenerative diseases and, eventually, help scientists discover tomorrow’s medicines.
"You can't predict what we’ll find. And that's the point,” added Bock. “Our country has historically invested in basic research for this reason, the unpredicted discoveries."
This story was adapted from a press release originally published by the University of Vermont.