Award Details:
Award Type: Catalyst
Award #: C-074
Proposal Title: Transplanting a Prokaryotic Oscillator to Animals to Restore Circadian Clock Function
PI(s): Michael Rust (UChicago) and Ravi Allada (NU)
Award Amount: $250,000.00
Application Cycle: Round 21 (Spring 2016)
Award Start Date: August 1, 2016
Award End Date: July 31, 2018
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.