Auto-regulation parts are commonly used regulation elements in gene networks which can be used in kinds of biological processes such as bio-oscillation, cell cycle, etc[1]. In nature, prokaryotic cells mostly employ negative feedback regulation to ensure their physiological homeostasis[2]. While in eukaryotic cells, they commonly regulate their homeostasis with both negative and positive feedback[3]. The positive feedback systems, on the basis of bi-stable or binary response in cells, are very important and powerful parts for synthetic biology research and development. In bi-stable systems, transition between two stable states could occur when the systems’ input parameters change. For example, the feedback system of cI/cro in bacteria phage λ triggers a binary switch that decides 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 control of signaling in Mammalian cells and plant cells are efficient regulation methods to response to the environment. For instance, in abscisic acid response pathway, ABF2 is tightly controlled through phosphorylation by SnRK2 and dephosphorylation by PP2CA[4].
Considering the functionality and significance of positive feedback and Kinases signal control to universal synthetic biology applications in bi-stable or even multi-stable systems, this year, HUST-China team tries to build a set of positive feedback fundamental tool kits for synthetic biology engineers. The systems we design will not only be adaptable to any input and output, but also can change its threshold to meet the requirement from different project purpose. As the positive feedback regulation system can transform an input pulse into stable states or outputs, it can also be applied as signal filter in circuits. Additionally, to make it a competent basic tool kits, we tries to provide both prokaryotic and eukaryotic versions, for synthetic biology engineers 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.