Transplanting a Prokaryotic Oscillator to Animals to Restore Circadian Clock Function

Type of Award: Catalyst
Date Awarded: June 2016
Award End Date: May 2018
Amount Awarded: $ 250,000.00
PI(s): Michael Rust, PhD, UChicago; Ravi Allada, MD, NU;

Abstract: Life on Earth evolved circadian clocks to optimally align behavior and physiology to the 24-hour environment. Molecular circadian oscillators are found in virtually all organs and tissues and disrupted circadian timing is a hallmark of cardiometabolic, oncological, and neuropsychiatric diseases. Major advances in understanding the fundamental biochemical basis of these circadian timers have been made, culminating in the ability to reconstitute a free running circadian oscillator in a test tube using only three cyanobacterial proteins. These discoveries in prokaryotes open up the possibility of applying synthetic biology approaches to recover and optimize circadian timing in animals using a transgenic oscillator network. Yet the transplantation of complex dynamic systems from prokaryotes to eukaryotes remains a major barrier. Building on our respective expertise in bacterial and animal clocks, we will engineer clock circuits based on bacterial oscillators, which we term "Kai-meras" to generate, restore and tune circadian rhythms in animals.