Scripps Research awarded a grant to the NIH BRAIN initiative to map undiscovered parts of the central nervous system

Throughout science and medicine, the brain remains one of the most mysterious and complex parts of the human body. Scripps Research Associate Professor Giordano Lippi (above), Ph.D., received a grant from the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) initiative of the National Institutes of Health (NIH) to develop a new technology that reveals a major neural component and improves our understanding of how the human brain works.

The highly regarded grant will provide $2.3 million in funding over one year, split equally 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,” that is, the set of mRNAs (the genetic material that contains protein-coding information) that are highly translated into proteins ( effectors of all cell functions).

“Much of the human brain is still a puzzle for researchers today, and we need improved tools to better understand the molecular mechanisms that underlie everything from cognition to behavior to disease,” says Lippi, who is an associate professor in the Department of Neuroscience. and Dorris Neuroscience Center, as well as Adjunct Professor in the Department of Neuroscience at UC San Diego. “I am honored to receive this grant and to help answer some of the biggest questions in neuroscience alongside a team of leading RNA experts, computational biologists, and molecular neuroscientists.”

Lippi and Yeo’s technological toolkit is known as Ribo-STAMP (Surveying Targets by Antibody-free Mutation Profiling), which measures – at the single-cell level – how often a ribosome (the synthesis machine proteins) binds to mRNAs. It is an excellent proxy for protein translation, the final step in protein synthesis. Current related technologies, such as single-cell RNA sequencing, rely solely on measuring mRNA levels, which is a poor predictor of protein levels. In other words, Ribo-STAMP shows the full picture of translation which is a much better representation of gene expression patterns in the brain.

Ribo-STAMP has the potential to shed light on this critical aspect of gene expression for the first time and help scientists better understand – and even predict – how the translatome impacts neurobiological processes underlying physiology. , plasticity and disease. To achieve this, the team, supported by the grant, will extend Ribo-STAMP to be used for different applications in neuroscience and to map translatoms of specific neural cell types.

“With this funding, we can fully develop the most informative and scalable molecular profiling technology and, therefore, finally discover the high-resolution brain translatome,” adds Lippi.

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