New $2.2 million grant will support the search for mammalian RNA sensors that could shed light on lithium biology and mental health.
The laboratory of Dr. Ronald Breaker, Sterling Professor of Molecular, Cellular and Developmental Biology (MCDB) and Molecular Biophysics and Biochemistry (MB&B), has received a three-year research grant totaling nearly $2.2 million from the John Templeton Foundation. The funding will support efforts to discover and characterize mammalian riboswitches that sense lithium and sodium ions.
Riboswitches are RNA molecules that selectively detect specific chemical signals and regulate gene expression in response to changes in their concentration. While most known riboswitches are found in bacteria, the Breaker laboratory recently discovered the first examples of these gene-regulatory RNAs in humans and other mammals.
Previous work from the laboratory identified bacterial riboswitches that sense lithium and sodium, revealing numerous genes involved in managing or exploiting the concentrations of these ions. Building on these findings, the new project will use advanced computational approaches to search for previously hidden ion-sensing RNAs in humans and related species.
“By using powerful computer searches, we can uncover otherwise hidden candidates for ion-sensing RNAs in humans and related species, and many are associated with genes involved in neuronal development and mental disorders,” said Breaker.
A major goal of the Templeton-funded project is to discover and validate candidate lithium-sensing riboswitches. The researchers hope these studies will provide new insights into the natural biological roles of lithium in human physiology and help explain how lithium functions as a therapeutic agent in the treatment of bipolar disorder.
Breaker emphasized the importance of foundation support for innovative research initiatives. “We were delighted to find that the program managers and staff at the Templeton Foundation were so engaged in evaluating our research proposal,” he said. “They understood and embraced the uncertainty inherent in our research, but also recognized that their support could make a huge difference for our initiative in lithium biology.”
The project will be conducted in Yale Science Building on Science Hill. Opened in 2019, the facility serves as a centerpiece of Yale’s continuing investment in state-of-the-art research infrastructure and supports a broad range of basic science research within Yale’s Faculty of Arts and Sciences.
Periodic table of the elements indicating elemental ions sensed by validated or candidate riboswitch classes. The presence of lithium sensing RNAs in humans would reveal the physiological importance of this ion.