Chemical control of PER2-CRY1 heterodimerization: impact on circadian oscillations. Circadian clocks are ~24 hr molecular oscillators present in essentially every mammalian cell. Dimerization of the key clock proteins PER2 and CRY1 is a critical switch-like event that initiates a cascade of downstream processes. Such a nonlinear switch is required for self-sustained oscillations. This projects aims at analysing both experimentally and with mathematical modelling the kinetics and dynamics of key events of circadian rhythm generation such as nuclear translocation or transcriptional regulation. E.g. by perturbing the PER2-CRY1 dimerization switch with rapidly acting chemical tools in combination with high-end live cell imaging, we anticipate obtaining a quantitative description in space and time of the mechanisms of circadian rhythm generation in living cells.
Prof. Dr. Achim Kramer (Charité Berlin)
Prof. Dr. Hans-Peter Herzel (Charité Berlin)