Caltech faculty members Mitchell Guttman and Markus Meister (PhD '87) have been selected to receive "high-risk, high-reward" grants from the National Institutes of Health (NIH) for cutting-edge work in biomedical science and neuroscience. Guttman's funded work could enable new methods to produce antibodies for any possible protein—a development with implications for both basic laboratory tests and clinical care. Meanwhile, Meister's research aims to explain arguably the core question of neuroscience: how the brain organizes human behavior.
Guttman, a Caltech professor of biology, is a recipient of an NIH Director's Transformative Research Award. These grants support projects that are "inherently risky and untested but have the potential to create or overturn fundamental paradigms," according to the NIH.
Guttman's research seeks to understand fundamental principles of biological regulation within the nuclei of cells. He and his lab have developed numerous genomic methods for mapping the higher-order three-dimensional organization of RNA and DNA in the nucleus. Many of these methods rely on a strategy called split-and-pool barcoding, in which samples are repeatedly divided, tagged with short DNA "barcodes," and pooled again, so that molecules bound together inside a cell end up carrying the same string of barcodes. This allows thousands of molecular interactions to be read out at once by DNA sequencing.
With the new funding, Guttman will apply this approach to developing reliable antibodies, a challenge that touches nearly every area of biomedical research. Scientists use antibodies to detect and measure proteins in everything from basic laboratory experiments to clinical diagnostic tests. However, high-quality antibodies exist for only a small fraction of the roughly 20,000 proteins in the human body. Using split-and-pool barcoding methods, Guttman will develop a platform to create molecules that bind to every human protein. The platform uses nanobodies—miniature antibodies modeled after those made naturally by camels and llamas—which can be produced and screened in enormous numbers in a test tube.
"Nearly every experiment that measures a protein depends on having a good antibody, and, for most human proteins, we simply don't have one," Guttman says. "A complete set would enable experiments that are impossible today, from measuring thousands of proteins within individual cells to mapping how proteins interact with DNA, RNA, and one another, and could ultimately lead to improved diagnostics and new therapies."
Meister, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences, is the recipient of an NIH Director's Pioneer Award, which "supports scientists with outstanding records of creativity pursuing new research directions to develop pioneering approaches to major challenges in biomedical, social science, and behavioral research."
Meister's research investigates large circuits of neurons to determine how they work. These brain structures consist of many neurons that have some anatomical and functional identity and exchange signals with other brain circuits. While his lab previously focused on circuits involved in visual processing, he is now exploring neural mechanisms responsible for rapid learning and task control.
With the Pioneer Award funding, Meister will investigate "the central question" motivating neuroscience: How does the brain organize the perplexing richness of human behavior? Many of our everyday activities—such as driving to work or making dinner—are composed of hundreds of distinct and brief tasks that are strung together to accomplish an overall goal. Researchers know very little about how the brain implements and coordinates these "microtasks" in a flexible and rapid succession.
"Our goal is to gain an understanding of hierarchical control of human behavior for the first time, all the way from deciding long-term goals to executing individual movements," Meister says. The work, he says, could improve treatments for neuropsychiatric disorders and help build better artificial intelligence systems for controlling the actions of robots, among other applications.
The NIH Common Fund "supports bold scientific programs that catalyze discovery across all biomedical and behavioral research," according to the organization's website.
In 2026, NIH issued seven Pioneer Awards, 42 New Innovator Awards, six Transformative Research Awards, and three Early Independence Awards, including those awarded to Guttman (R01CA325352-01) and Meister (DP1NS155489-01). Funding for the grants comes from the NIH Common Fund, the National Institute of Environmental Health Sciences, the National Institute on Deafness and Other Communication Disorders, and the Office of Research Innovation, Validation, and Application.