Molecular Chronobiology - Merrow Lab
We are all ruled by our circadian clocks ! They specify when we sleep and wake, how well we perform, how we feel. They even regulate the speed of our heartbeat! The Molecular Chronobiology lab at the IMP tries to explain circadian behavior from the lowest levels of complexity, building up a network of oscillating effector molecules, that eventually behave as a circadian clock.
What are our tools? We favour simple model systems, such as human tissue culture cells, Neurospora crassa, Saccahromyces cerevisiae and C. elegans. We typically compare the entrained phase (when oscillations occur in a given zeitgeber cycle) with free running period, or with other entrainment protocols, to try to understand how the clock is functioning in pseudo-natural conditions. We follow molecular oscillations from RNA to protein to post-transcriptional modifications, when possible, using high-throughput methods (luciferase gene fusions and GFP).
What have we described with these methods? When ‘clock-less’ mutant Neurospora strains are entrained in temperature cycles, they behave as though they still have a clock, anticipating zeitgeber transitions and revealing a circadian machinery beyond the known clock genes . Recent insights go further, specifying oscillations in the redox state of a broadly conserved molecule as an indication of a mechanism that likely precedes the transcriptional feedback loop that is thought of as crucial most clocks . We have also shown evidence of a clock in the powerful cellular model Saccharomyces cerevisiae , bringing this toolkit to circadian clocks research.
At the IMP, we are concentrating on clocks in cells and the clock in a simple animal, C. elegans .