Scripps Research scientists honored with prestigious CZI awards to address diseases tied to aging
Christopher Parker and Giordano Lippi are unraveling the metabolic and protein mechanisms, respectively, that go awry in aging and disease—including Alzheimer’s.
February 29, 2024
LA JOLLA, CA—How do our cellular mechanics change as we age, including in diseases like Alzheimer’s? Two Scripps Research scientists have been granted prestigious awards from the Chan Zuckerberg Initiative (CZI) to help answer that expansive question.
Christopher Parker, PhD, associate professor of chemistry, is a co-recipient of an Exploratory Cell Networks grant to chart the RNA metabolic networks that contribute to aging and disease. At the same time, Giordano Lippi, PhD, associate professor of neuroscience, has been granted the Collaborative Pairs Pilot Project Award to determine how a type of non-coding RNA impacts neurodegeneration. Both projects will reveal critical insights about the mechanisms that differentiate health from disease.
Shedding light on RNA metabolism
Dysregulation of RNA processing can lead to altered gene regulation and disrupted cellular responses, but there is much about this process that remains unknown. The Exploratory Cell Networks grant will provide $1.25 million in funding to Parker’s lab over the course of three years, supporting the creation of strategies to investigate dynamic regulation RNA interactions, processing and metabolism. Parker will work alongside other grantees at neighboring institutions, including Christian Metallo, PhD, professor in the Molecular and Cell Biology Laboratory and Daniel and Martina Lewis Chair at the Salk Institute for Biological Studies; and Eugene Yeo, PhD, professor of Cellular and Molecular Medicine, and Nigel Goldenfeld, PhD, the Chancellor’s Distinguished Professor of Physics, at the University of California, San Diego. Together, they will use these technologies to clarify how cells respond and adapt to genetic and environmental stresses. This includes aging-related diseases linked to RNA dysregulation, such as Alzheimer’s disease.
“I am honored to receive this grant from the Chan Zuckerberg Initiative, which will empower our collaborative efforts to unravel the complex interplay between RNA and associated protein regulators,” Parker says. “Working hand-in-hand with other esteemed institutions across San Diego, we aspire to uncover new insights that could shape our understanding and treatment of different diseases, particularly those influenced by aging.”
Collaboration is a central component of the Exploratory Cell Networks grants, with each award comprising researchers from at least three different institutions. By building these regional networks of investigators, CZI intends to unite technology development and accelerate the grant’s overarching goal: to better understand health and disease.
“We believe that scientific collaborations bring together new ideas and approaches that rapidly accelerate the pace of progress, making it natural for us to foster these enabling, cross-lab partnerships,” said Scott Fraser, CZI Vice President of Science Grant Programs. “Collaboration and building communities of researchers are central to our grantmaking strategy, and we’re excited to see what our new Exploratory Cell Networks teams will accomplish.”
At Scripps Research, Parker’s lab develops new tools and technologies to discover how proteins function in every human cell type, with the intent to develop effective therapeutics for a wide range of human diseases. Recently, he published a Nature Chemical Biology study highlighting a new technology that uncovers the ‘druggable’ sites on proteins for any human disease. In a separate Nature Chemical Biology study, Parker and his colleagues developed a small molecule that blocks the activity of a protein linked to autoimmune diseases, including lupus and Crohn’s disease.
A new approach to treating neurodegeneration
While aging often correlates with neurodegenerative diseases, how the aging brain becomes susceptible to these conditions is still unknown. With the Collaborative Pairs Pilot Project Award, Lippi will work with Eugenio Fornasiero, PhD, group leader in the Department of Neuro- and Sensory Physiology at the University Medical Center Göttingen, to understand the role and therapeutic potential of a type of RNA called microRNA (miRNA) in aging and neurodegeneration. Lippi and Fornasiero will receive $200,000 over 18 months, while also receiving support, mentoring and collaborative interactions of CZI’s Neurodegeneration Challenge Network.
CZI developed the Collaborative Pairs Pilot Project Awards to catalyze new collaborations and scientific partnerships, while springboarding early-stage projects they recognize as “bold, creative and ‘out-of-the-box.’”
For Lippi and Fornasiero’s project, they will be investigating how miRNA networks impact protein dynamics in the context of aging-related diseases. miRNAs are small, single-stranded molecules of RNA that, unlike their mRNA counterparts, do not code for proteins. Instead, they regulate which genes are turned on and off in the cell. Lippi and Fornasiero will explore how these miRNA networks affect protein production and degradation—particularly what goes awry during the aging process and corresponding diseases.
In previous research, scientists have found that proteins associated with neurodegenerative diseases aren’t replaced as efficiently, causing the brain to accumulate molecular damage. Lippi and Fornasiero are striving to identify the specific miRNA nodes that can prevent—or even reverse neurodegeneration—when targeted. To do this, they will use a new model that precisely maps miRNA-target interactions across different brain cells.
“I am deeply grateful for CZI’s support, as it fuels our pursuit to unravel the complex role of miRNA in shaping protein dynamics, while holding promise for transformative insights into neurodegenerative diseases,” says Lippi. “We aim to illuminate new paths of potentially treating these devastating diseases, which impact millions of people around the world.”
About Scripps Research
Scripps Research is an independent, nonprofit biomedical institute ranked one of the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more at www.scripps.edu.
About the Chan Zuckerberg Initiative
The Chan Zuckerberg Initiative was founded in 2015 to help solve some of society’s toughest challenges — from eradicating disease and improving education to addressing the needs of our local communities. Our mission is to build a more inclusive, just, and healthy future for everyone. For more information, please visit chanzuckerberg.com.
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