Final Report Summary - CDGMP (Time, space and speed: cdGMP signaling in cell behavior and reproduction.)
Our work has shown that oscillatory waves of c-di-GMP are responsible for Caulobacter cell cycle progression and cell fate determination. A systematic analysis has uncovered the network components responsible for the oscillation and asymmetric distribution of c-di-GMP during division. We have developed novel tools to identify proteins that bind c-di-GMP and we have determined how the activity of these proteins is regulated in time and space and how this in turn leads to the activation of individual cellular processes like motility, surface adherence or cell division. Key findings of our work include the discoveries that c-di-GMP directly interferes with phosphorylation networks by modulating the activity of core sensor histidine kinases; that bacteria can utilise their rotary flagellar motors as tactile sensors to rapidly increase c-di-GMP levels and induce surface adherence; and that the c-di-GMP network directly interferes with other small molecules like ppGpp to modulate cell growth and metabolism. Overall, this work established important regulatory paradigms and concepts that can be directly related to studies aiming at uncovering the role of c-di-GMP in less tractable but medically relevant human and animal pathogens.