Across science and medicine, the brain remains one of the human body’s most mysterious and complex parts. Scripps Research associate professor Giordano Lippi (above), Ph.D., has been awarded a grant from the National Institutes of Health (NIH) Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop a new technology that reveals a major neural component and enhances our understanding of human brain function.
The highly regarded grant will provide $2.3 million in funding over one year, split evenly through a collaboration between Lippi’s lab and the Gene Yeo lab at UC San Diego. This funding will help advance a technology system that maps the brain’s “translatome”— the entire collection of mRNAs (the genetic material that carries protein-coding information) that are highly translated into proteins (the effectors of all functions in the cell).
“So much of the human brain is still a puzzle to researchers today, and we need enhanced tools to better understand the molecular mechanisms underlying everything from cognition to behavior to disease,” says Lippi, who is an associate professor both in the Department of Neuroscience and Dorris Neuroscience Center, as well as an adjunct professor in the Department of Neurosciences at UC San Diego. “I am honored to receive this grant and help answer some of neuroscience’s biggest questions alongside a team of leading RNA experts, computational biologists, and molecular neuroscientists.”
Lippi and Yeo’s technology toolkit is known as Ribo-STAMP (Surveying Targets by Antibody-free Mutation Profiling), which measures — at the single-cell level — how frequently a ribosome (the protein synthesis machine) binds to mRNAs. This is an excellent proxy for protein translation, the final step of protein synthesis. Current related technologies like single-cell RNA sequencing rely on measuring only mRNA levels, which is a poor predictor of protein levels. In other words, Ribo-STAMP shows the full translational picture that is a much better representation of gene expression patterns in the brain.
Ribo-STAMP has the potential to bring this critical aspect of gene expression to light for the first time and help scientists to understand better — and even predict — how the translatome impacts the neurobiological processes underlying physiology, plasticity, and disease. To achieve this, the team, supported by the grant, will expand Ribo-STAMP to be used for different neuroscience applications and to map the translatomes of specific neural cell types.
“With this funding, we can fully develop the most informative and scalable molecular profiling technology, and as a result, finally uncover the brain’s translatome at high resolution,” Lippi adds.
