Auto-regulation parts are commonly used regulation elements in gene networks which form kinds of biological processes such as bio-oscillation, cell cycle and etc[1]. In nature, prokaryotic cells mostly employ negative feedback regulation to ensure their physiological homeostasis[2], while eukaryotic cells commonly regulate their homeostasis with both negative and positive feedback systems[3]. The positive feedback systems, on the basis of bi-stable or binary response in vivo, are very important and powerful parts for synthetic biology researches. In bi-stable systems, transition between two stable states could occur when the system’s input signal varies. For example, the feedback system of CI/Cro in bacteriophage λ triggers a binary switch which will decide the fate of its host cell.
Fig1: How CII orchestrates the choice between lytic and lysogenic development with positive feedback.
And we also noticed that kinases, involved in signal transduction, are efficient regulation elements. For instance, in abscisic acid response pathway, ABF2 is tightly controlled by the phosphorylation function of SnRK2.2 and the dephosphorylation effect of PP2CA[4].
Considering the functionality and significance of auto-regulation parts and kinases in regulation networks, this year, we, HUST-China, tries to build a positive feedback fundamental toolkit for synthetic biology engineers. The systems we designed will not only be adaptable to any input and output intensity, but also can change its threshold to meet the requirements of different project purposes. As positive feedback regulation systems can transform an input signal into stable states or outputs, it can be applied as signal filters in genetic circuits. Additionally, to make our toolkit more competent, we tries to provide both prokaryotic and eukaryotic versions for synthetic biology researchers to compare and select for further application.
[1] Feedback control of intercellular signaling in development. Nature, 408, 313-319.
[2] From specific gene regulation to genomic networks: a global analysis of transcriptional regulation in E.coli. BioEssays, 20, 433-440.
[3] Autoregulation of eukaryotic transcription factors. Prog. Nucleic Acid Res. Mol. Biol., 60, 133-168.
[4]Soon, F. F., Ng, L. M., Zhou, X. E., West, G. M., Kovach, A., Tan, M. H., . . . Xu, H. E. (2012). Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases. Science, 335(6064), 85-88.