Abstract: One of the key objectives of synthetic biology is to design artificial biological systems in order to better understand their natural counterparts. Through the use of known biological components, the complexities of the regulatory network can be simplified dramatically during the reconstruction process. In this dissertation, I will present my contribution on the understanding of biological oscillation through the creation of a synthetic oscillator designed to be integrated within the central metabolism in Escherichia coli. To achieve transcriptional and metabolic integration characteristic of natural oscillators, the synthetic gene circuit in designed to be integrated within the central metabolic path-way of Escherichia coli K12. Glycolytic flux is the main driving force to generate oscillation through a signaling metabolite, acetyl phosphate (AcP). By placing two enzymes inter-converting two metabolite pools under the transcriptional control by AcP, the system oscillates when the glycolytic rate exceeds a critical value. Bifurcation analysis revealed the boundaries of oscillation, which were verified experimentally. This work demonstrates the possibility of utilizing metabolic flux as a control factor in system-wide oscillation and the predictability of de nova designed gene-metabolic circuit using nonlinear dynamic analysis. The resulting gene-metabolic circuit is an example of a nano-sensor that responds to intercellular concentration of acetate as well as metabolic flux in E. coli at a single cell level. From a biological standpoint, the synthetic gene-metabolic oscillator can he considered as one model system to further our understanding of natural biological oscillators. The simplicity of the design enables detail examination of the molecular mechanisms which give rise to oscillation. The effect of transcriptional dynamics is examined through the generation of variants of the synthetic oscillator. While retaining the same topology, these variants differ by the promoters strengths. In addition, based on observation of the cells containing a non-native gene circuit, incompatibility issues sometimes arise. The design principle and approach gained through the characterization of the synthetic oscillator can be extended and applied for measuring biological signals and the production or consumption of other biochemicals.