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Scripps Makes Brain Research Breakthroughs

LIFE SCIENCE: NIH Awards Lead to New Understanding of Neurology

Scripps Research is giving the field of neuroscience a lot to think about.

On Sept. 1, Scripps announced that Dorris Neuroscience Center associate professor Giordano Lippi, PhD, was awarded a $2.3 million 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 grant will be split through a collaboration between Lippi’s lab and the Gene Yeo lab at UC San Diego to fund development of a technology system that maps the brain’s “translatome” — the collection of mRNAs that are highly translated into proteins.

Giordano Lippi, PhD
Associate Professor
Dorris Neuroscience Center

“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,” Lippi said, who is also 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 single-cell level — how frequently a ribosome (the protein synthesis machine) binds to mRNAs. The process more accurately predicts protein levels than current methods and shows a much better representation of gene expression patterns in the brain.

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Ribo-STAMP has the potential to bring this aspect of gene expression to light and help scientists better understand and possibly 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 added.

The Language of Fat

Scripps also announced on Sept. 1 that researchers – in part, funded by the NIH Director’s New Innovator Award Program – made a breakthrough in understanding how fat tissue communicates with the brain, which could potentially lead to treatments for obesity or metabolic disease.

In a report in the journal Nature, Scripps scientists announced that recently identified sensory neurons carry a stream of messages from adipose tissue to the brain.

In mammals, fat tissue stores energy in the form of fat cells and, when the body needs energy, releases those stores. It also controls a host of hormones and signaling molecules related to hunger and metabolism. In diseases including diabetes, fatty liver disease, atherosclerosis and obesity, that energy storage and signaling often goes awry.

Ardem Patapoutian, PhD 
Professor, Dorris Neuroscience Center 
Scripps Research

“This is yet another example of how important sensory neurons are to health and disease in the human body,” says co-senior author and professor Ardem Patapoutian, PhD,  who is also a 2021 Nobel Prize laureate and a Howard Hughes Medical Institute investigator.

Researchers have long known that nerves extend into fat tissue, but suspected they weren’t sensory neurons that carry data to the brain.  It was assumed that hormones passively floating through the blood were the way that a person’s fat — called adipose tissue — could send information related to stress and metabolism to the brain.

Using new imaging tools, researchers tracked the paths of neurons as they snaked into adipose tissue and found they connected to an area of the brain where all sensory neurons originate. Then the researchers used a new technique to selectively destroy small subsets of sensory neurons in the adipose tissue using a targeted virus.

Li Ye, PhD
Abide-Vividion Chair in Chemistry and Chemical Biology 
Scripps Research

The experiments revealed that when the brain doesn’t receive sensory messages from adipose tissue, the body will burn more fat. The findings suggest that the sensory neurons and sympathetic neurons might have two opposing functions, with sympathetic neurons needed to turn on fat burning, and sensory neurons required to turn these programs down.

“This tells us that there’s not just a one-size-fits-all instruction that brain sends adipose tissue,” Ye said. “It’s more nuanced than that; these two types of neurons are acting like a gas pedal and a brake for burning fat.”

The team doesn’t yet know exactly what messages the sensory neurons convey to the brain from adipose tissue, only that the connections and communications are key for keeping fat healthy. They are planning future research into what the neurons are sensing and whether other similar cells exist in additional internal organs.

Scripps Research
Founded: 1924
CEO: Peter Shultz
Business: Medical and scientific research institute
Headquarters: La Jolla
Employees: 2,400+
Revenue: Over $320 million (2020)
Website: scripps.edu
Notable: Scripps Research holds over 1,100 U.S. patents.

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