Instytut Podstawowych Problemów Techniki
Polskiej Akademii Nauk


David A Turner

Ostatnie publikacje
1.  Turner D., Paszek P., Woodcock D. J., Nelson David E., Horton Caroline A., Yunjiao W., Spiller David G., Rand D. A., White M., Harper C. V., Physiological levels of TNFalpha stimulation induce stochastic dynamics of NF-kappaB responses in single living cells, Journal of Cell Science, ISSN: 0021-9533, DOI: 10.1242/jcs.069641, Vol.123, No.16, pp.2834-2843, 2010

Nuclear factor kappa B (NF-kappaB) signalling is activated by cellular stress and inflammation and regulates cytokine expression. We applied single-cell imaging to investigate dynamic responses to different doses of tumour necrosis factor alpha (TNFalpha). Lower doses activated fewer cells and those responding showed an increasingly variable delay in the initial NF-kappaB nuclear translocation and associated IkappaBalpha degradation. Robust 100 minute nuclear:cytoplasmic NF-kappaB oscillations were observed over a wide range of TNFalpha concentrations. The result is supported by computational analyses, which identified a limit cycle in the system with a stable 100 minute period over a range of stimuli, and indicated no co-operativity in the pathway activation. These results suggest that a stochastic threshold controls functional all-or-nothing responses in individual cells. Deterministic and stochastic models simulated the experimentally observed activation threshold and gave rise to new predictions about the structure of the system and open the way for better mechanistic understanding of physiological TNFalpha activation of inflammatory responses in cells and tissues.

Słowa kluczowe:

Afiliacje autorów:
Turner D. - inna afiliacja
Paszek P. - IPPT PAN
Woodcock D. J. - University of Warwick (GB)
Nelson David E. - inna afiliacja
Horton Caroline A. - inna afiliacja
Yunjiao W. - inna afiliacja
Spiller David G. - inna afiliacja
Rand D. A. - University of Warwick (GB)
White M. - inna afiliacja
Harper C. V. - University of Manchester (GB)

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