Instytut Podstawowych Problemów Techniki
Polskiej Akademii Nauk


F. Unitt John

Ostatnie publikacje
1.  Ashall L., Horton Caroline A., Nelson David E., Paszek P., Harper Claire V.V., Sillitoe K., Ryan S., Spiller David G., Unitt John F., Broomhead David S., Kell Douglas B., Rand David A.A., Sée V., White Michael R.R., Pulsatile Stimulation Determines Timing and Specificity of NF-κB-Dependent Transcription, Science, ISSN: 0036-8075, DOI: 10.1126/science.1164860, Vol.324, No.5924, pp.242-246, 2009

The nuclear factor κB (NF-κB) transcription factor regulates cellular stress responses and the immune response to infection. NF-κB activation results in oscillations in nuclear NF-κB abundance. To define the function of these oscillations, we treated cells with repeated short pulses of tumor necrosis factor–α at various intervals to mimic pulsatile inflammatory signals. At all pulse intervals that were analyzed, we observed synchronous cycles of NF-κB nuclear translocation. Lower frequency stimulations gave repeated full-amplitude translocations, whereas higher frequency pulses gave reduced translocation, indicating a failure to reset. Deterministic and stochastic mathematical models predicted how negative feedback loops regulate both the resetting of the system and cellular heterogeneity. Altering the stimulation intervals gave different patterns of NF-κB–dependent gene expression, which supports the idea that oscillation frequency has a functional role.

Afiliacje autorów:
Ashall L. - inna afiliacja
Horton Caroline A. - inna afiliacja
Nelson David E. - inna afiliacja
Paszek P. - inna afiliacja
Harper Claire V.V. - University of Manchester (GB)
Sillitoe K. - inna afiliacja
Ryan S. - inna afiliacja
Spiller David G. - inna afiliacja
Unitt John F. - inna afiliacja
Broomhead David S. - inna afiliacja
Kell Douglas B. - inna afiliacja
Rand David A.A. - University of Warwick (GB)
Sée V. - inna afiliacja
White Michael R.R. - University of Manchester (GB)

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