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, involved in signal transduction in mammalian cells and plant cells, are efficient regulation tools. For instance, in abscisic acid response pathway, ABF2 is tightly controlled through phosphorylation by SnRK2.2 and dephosphorylation by PP2CA[4].
Considering the functionality and significance of auto-regulation parts and kinases, this year, we, HUST-China, tries to build a fundamental toolkit for synthetic biology researchers, using positive feedback systems. The toolkit we designed can not only be adapted to various input and output, but also can change its threshold to satisfy the requirements of different projects. As the positive feedback regulation system can transform an input signal into stable states of outputs, it can be applied as a signal filter in gene circuits. Additionally, to make it a competent basic toolkit, 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.