Genetic Oscillations and Stress Responses in Eucaryotes
by
Mogens Høgh Jensen(Niels Bohr Institut)
→
Europe/Stockholm
Description
Stress responses and genetic regulations are studied in the systems centered about the transcription factors NFkB, p53 and Hes1 [1-3]. We identify the central feed-back loops and find that most responses are related to oscillatory behavior. Oscillations are possible when time delays are present, either by directly introducing a delay, by many steps in the loops or by saturated degradation. The oscillations are important for cell apoptosis and the control of inflammation [1-3]. The potential physiological role is also discussed by exploring whether oscillatory signals can encode more information than steady-state signals. Hes1 is an essential regulator in embryo segmentation of the Wnt system. Here the oscillations define the boundaries for each somite formation and thus leads to spatial periodicity [4]. We finally show how genetic oscillations can be coupled to cell-to-cell interactions in space [5].
[1] S. Krishna, M.H. Jensen and K. Sneppen, "Spiky oscillations in NF-kappaB signalling", Proc.Nat.Acad.Sci. 103,10840-10845 (2006).
[2] G. Tiana, S. Krishna, S. Pigolotti, M.H. Jensen and K. Sneppen, "Oscillations and temporal signalling in cells", Physical Biology 4, R1-R17 (2007).
[3] A. Hunziker, M.H. Jensen and S. Krishna, "Stress-specific response of the p53-Mdm2 feedback loop", BMC Systems Biology, (2010).
[4] P.B. Jensen, L. Pedersen, S. Krishna and M.H. Jensen, "A Wnt Oscillator Model for Somitogenesis", Biophys. Journ.,98, 943-950 (2010).
[5] M.H. Jensen, S. Krishna and S. Pigolotti, "The Repressor-Lattice: Feedback, Commensurability, and Dynamical Frustration, Phys. Rev. Lett. 103, 118101 (2009).
