Development of new molecular tools to advance understanding of calcium release activated calcium (CRAC) channels in the plasma membrane is the focus of a nearly $800,000 grant from the National Science Foundation (NSF) to a University of Maine-led research team.
The molecular tools — novel compounds called light-operated CRAC channel inhibitors (LOCIs) — will allow researchers to control the function of CRAC channels to better understand their role in cell biology.
CRAC channels are key proteins that affect calcium entry and signaling in cells. The channels control such cellular activities as cell migration and proliferation, and gene expression. However, little is known about the molecular, biophysical and biochemical mechanisms that regulate the highly selective release of calcium. Calcium is one of the most important signaling molecules in living cells.
The grant, funded by NSF and the U.S.-Israel Binational Science Foundation, enables an international collaboration between Michael Kienzler, UMaine assistant professor of chemistry, and assistant professor Raz Palty at the Technion in Haifa, Israel.
Kienzler’s research focuses on the synthesis and evaluation of new light-activated molecules for biological applications. His lab is developing a series of LOCIs photoswitches designed to modulate CRAC channel activity. By incorporating photoswitches into the LOCI compounds, their activity can be turned on and off by shining different colors of light on them, providing a high degree of precision and control in experiments.
The UMaine Chemistry Department recently upgraded its facilities with a state-of-the-art, 500 MHz nuclear magnetic resonance spectrometer, made possible by a more than $535,000 grant from NSF’s Major Research Instrumentation and Chemistry Research Instrumentation programs. This new instrument is an essential tool for characterizing the LOCI compounds.
The goal of the research is to determine if LOCIs can be used to control calcium-dependent cellular responses and, ultimately, manipulate such functions as gene expression and cellular migration. The research team’s novel opto-genetic and opto-pharmacological approaches could provide rapid and reversible remote control of CRAC channel signals — an important component in a wide range of cellular processes and particularly immune system function.