Nov. 27, 2023 —  Metabolites may not be a word you hear often, but for investigators in the department of biochemistry and molecular biology, they represent the final frontier of discovery in spatial biology as seen in the newly opened UF Center for Advanced Spatial Biomolecule Research, or CASBR.

Cells are the basic biological units of life. But even smaller than cells are the metabolites produced along every cellular process. From small molecules such as amino acids and antioxidants, metabolites are the intermediary and end products of the body’s metabolism, the chemical reactions needed to sustain life. Directed by Ramon Sun, Ph.D., an associate professor biochemistry and molecular biology, CASBR is the sole center on campus providing state-of-the-art spatial biology services to delve into the human metabolism.

The center’s launch in February follows Sun’s arrival to the UF College of Medicine in 2022 as the Anne and Oscar Lackner Endowed Eminent Scholar. A biochemist by trade, he focuses part of his research on spatial metabolism, an emerging approach to studying metabolites at a large scale. He also leads the Sun Lab, which focuses on the spatial biology of metabolic diseases such as cancer and dementia.

“It’s the metabolites that determine who we are,” Sun said. “A gene mutation doesn’t do anything by itself, it’s just a piece of genetic material. It has to be translated and produced into metabolites for it to be disease-causing.”

Before UF, Sun’s first stint as faculty came while at the University of Kentucky. There, he met and began closely collaborating with Matthew Gentry, Ph.D., current chair of the department of biochemistry and molecular biology at UF, and Craig Vander Kooi, Ph.D., now a professor in the department. The trio pursued research on Lafora disease, a rare genetic form of progressive epilepsy, and soon shaped a shared mission in spatial metabolism that they hold to this day. So, when UF first acquired the high-tech multi-imaging systems that make up the current center, they jumped at the opportunity and headed south together. Gentry and Vander Kooi work alongside Sun as co-directors of CASBR.

Sun’s research is disease “agnostic,” meaning that its focus is on understanding the fundamental biology and mechanisms that make the human body work. Where other labs may have a focus on one biochemical pathway for a disease, Sun and the center seek projects on cancer, Alzheimer’s disease, epilepsy and many other forms of rare disease. All this advanced work has been enabled by the high-end imaging instruments made available to him by UF.

“To give an example, the MALDI imager I had back home was like an iPhone camera,” Sun noted. “These new ones at UF are like DSLR cameras.”

CASBR houses two mass spectrometry MALDI timsTOF fleX instruments that serve metabolomics-based research. MALDI stands for matrix assisted laser desorption/ionization, which describes the method by which a laser shoots down onto an organic tissue sample suspended in a prepared matrix. In a split second, the sample and matrix are ionized through energy transfer from the powerful laser.

It’s a technique in metabolomics that has been touted as a technology to watch in 2023 by Nature Journal for its ability to allow scientists to discern the inner workings of biology at the single-cell level as never seen before.

“You’re really looking at a melting pot of all these cells together,” Sun said. “There’s no way of separating them. But now, the MALDI instrument is essentially acting like Google Maps for the body. It suddenly gives you very detailed roads, streets, buildings that haven’t been previously available and visible to investigators.”

The center also carries other instruments that contribute to spatial metabolism research, such as a PhenoImager HT and a hydrogen deuterium exchange with mass spectrometry machine. Taken as a whole, these tools are run by CASBR on behalf of UF and non-UF researchers looking to analyze tissue or protein samples from their own ongoing studies.

CASBR services are present throughout the university: the center has collaborated with the Evelyn F. and William L. McKnight Brain Institute, the Center for Translational Research in Neurodegenerative Disease, the Breathing Research and Therapeutics Center and the UF Health Cancer Center. They’ve also gone outside Gainesville city limits: samples have been sent in from researchers at other R1 institutions, including Harvard, MIT, Stanford University and Johns Hopkins University.

The real-world impact has been just as far-reaching. For example, a current study from the Sun Lab made use of CASBR to determine how high-carb and high-fat diets, often seen in fast food meals, correlate with an accelerated tumor incidence in lung cancer among lower-income Americans who smoke — even when compared with higher-income counterparts.

“This work can be immediately actionable,” Sun said. “It is policy-shifting because you can use it to advocate for more fresh produce availability for these people who live in disadvantaged rural areas.”

Other uses have targeted diseases related to the brain. Charles Michael Soto, a CASBR lab technician and Sun Lab member, is helping to manage the CASBR instruments for the analyses of neurodegenerative conditions such as Lafora disease and Alzheimer’s disease.

“The ability to look at brain tissue on a spatial level isn’t something I’ve experienced or seen before outside this lab,” Soto said. “Between all the different equipment you see, the different people you meet and the different technology you’re exposed to and are repairing, it’s all just a ton of good experience.”

Sun is also pushing CASBR further into the future by incorporating the HiPerGator supercomputer into his lab’s work. Using computer vision, a form of AI that allows machines to interpret visual information, the Sun Lab and Li Chen, Ph.D., an associate professor in the department of biostatistics in the College of Public Health and Health Professions and the College of Medicine, are building a visual atlas of metabolites to be used as a guide for investigators worldwide.

For now, though, researchers can turn to CASBR for their tissue sample needs and to answer ambitious biological questions.

“We’re operating on the basis of good science,” Sun said. “If the science is interesting and novel, we’re always happy to help give researchers another dimension of what they can see because of our technologies.”