Abstract
The study of biological systems dynamics requires elucidation of the transitions of steady states. A “small perturbation” approach can provide important information on the “steady state” of a biological system. In our experiments, small perturbations were generated by applying a series of repeating small doses of ultraviolet radiation to a human keratinocyte cell line, HaCaT. The biological response was assessed by monitoring the gene expression profiles using cDNA microarrays. Repeated small doses (10 J/m2) of ultraviolet B (UVB) exposure modulated the expression profiles of two groups of genes in opposite directions. The genes that were up-regulated have functions mainly associated with anti-proliferation/anti-mitogenesis/apoptosis, and the genes that were down-regulated were mainly related to proliferation/mitogenesis/anti-apoptosis. For both groups of genes, repetition of the small doses of UVB caused an immediate response followed by relaxation between successive small perturbations. This cyclic pattern was suppressed when large doses (233 or 582.5 J/m2) of UVB were applied. Our method and results contribute to a foundation for computational systems biology, which implicitly uses the concept of steady state.
Highlights
Systems biology studies the dynamics of networks of interacting molecules in living organisms [1,2]
We set up experiments (Figure 1A) to study gene expression profiles of HaCaT cells during multiple irradiations of ultraviolet B (UVB)
We used a new approach of repeated small perturbations to demonstrate the existence of a transcriptional steady state, which is a crucial step in life maintenance and an essential assumption of computational systems biology [15,16,17]
Summary
Systems biology studies the dynamics of networks of interacting molecules in living organisms [1,2]. According to the new paradigm for biomedical study proposed by Kitano [2], a systems framework for biology has at least four key properties: I) system structure, II) system dynamics, III) control method, and IV) design method. An adequate experimental method of studying biological systems dynamics, the transitions of physiological states (defined [3,4,5] according to various factors such as amounts of metabolites corresponding to metabolic states or RNA expression profiles for transcriptional states), has not yet been developed. To maintain the physiological robustness, a variety of levels of robustness, including transcriptomic expression, are critical. This can be referred as the transcriptomic expression steady state
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