I will discuss two topics. Firstly, coupling of the circadian clock and cell cycle in mammalian cells. Together with the labs of Franck Delaunay (Nice) and Bert van der Horst (Rotterdam) we have developed a pipeline involving experimental and mathematical tools that enables us to track through time the phase of the circadian clock and cell cycle in the same single cell and to extend this to whole lineages. We show that for mouse fibroblast cell cultures under natural conditions, the clock and cell cycle phase-lock in a 1:1 fashion. We show that certain perturbations knock this coupled system onto another periodic state, phase-locked but with a different winding number. We use this understanding to explain previous results. Thus our study unravels novel phase dynamics of 2 key mammalian biological oscillators. Secondly, I present a radical revision of the Nrf2 signalling system. Stress responsive signalling coordinated by Nrf2 provides an adaptive response for protection against toxic insults, oxidative stress and metabolic dysfunction. We discover that the system is an autonomous oscillator that regulates its target genes in a novel way.
