An “And-Gate” for Optogenetic Control Of Protein Kinases

Type of Award: Catalyst
Date Awarded: September 2013
Award End Date: August 2015
Amount Awarded: $ 200,000.00
PI(s): Andrei Karginov, PhD, UIC; Michael Glotzer, PhD, UChicago;

Abstract: A vast array of cellular behaviors are regulated by a class of enzymes called kinases that catalyze the covalent addition of negatively charged phosphate groups to specific sites on other proteins. This simple, reversible modification controls diverse processes including, but not limited to, cellular organization, intercellular communication, as well as cell growth, division, migration, and death. An individual kinase can regulate distinct processes by acting on different substrates at different subcellular sites. In order to decipher the complex functions of different kinases, it would be extremely beneficial to be able to control the time, place, and duration in which a particular kinase is active. However, we currently lack the tools to control kinases with this precision. In independent work, Drs. Karginov and Glotzer had developed tools that address portions of this goal. Dr. Karginov developed a method to control kinases by the use of a small molecule activator; this provides a degree of temporal control. Dr. Glotzer's lab has developed a method to control protein- protein interactions with light; this provides general spatial and temporal control, but not control of kinase activity. By combining our technologies and refining the hybrid technology, we seek to generate active forms of specific kinases at any desired subcellular site. If successful, these tools will further our understanding of the functions of this critically important class of enzymes.