Thesis (M.S.)--University of North Carolina Wilmington, 2007. / Includes bibliographical references (Leaves: 62-68)

Thesis (Ph. D.)--University of Sydney, 2002. / Title from title screen (viewed Apr. 28, 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Molecular and Microbial Biosciences, Faculty of Science. Includes bibliographical references. Also available in print form.

Thesis (M.C.S.)--Carleton University, 2001. / Includes bibliographical references (p. 87). Also available in electronic format on the Internet.

Thesis (Ph.D.)--Aberdeen University, 2009. / Title from web page (viewed on July 14, 2009). Includes bibliographical references.

The goal of Synthetic Biology is to engineer systems from biological parts. One class of systems are those whose purpose is to process information. My work seeks to build transcription-based devices for use in combinational digital logic. Preliminary characterization experiments show that existing devices fall short of desired device behavior. I propose to develop a novel implementation of transcription-based logic by designing synthetic transcription factors from well-characterized DNA binding and dimerization domains. Initial modeling work serves to inform design of these devices. / Poster presented at the 2005 ICSB meeting, held at Harvard Medical School in Boston, MA.

The goal of Synthetic Biology is to engineer systems from biological parts. One class of systems are those whose purpose is to process information. My work seeks to build transcription-based devices for use in combinational digital logic. Preliminary characterization experiments show that existing devices fall short of desired device behavior. I propose to develop a novel implementation of transcription-based logic by designing synthetic transcription factors from well-characterized DNA binding and dimerization domains. Initial modeling work serves to inform design of these devices. / Poster presented at the 2005 ICSB meeting, held at Harvard Medical School in Boston, MA.

The engineering of biological systems with predictable behavior is a challenging problem. One reason for this difficulty is that engineered biological systems are embedded within complex and variable host cells. To help enable the future engineering of biological systems, we are studying and optimizing the interface between an engineered biological system and its host cell or ``chassis''. Other engineering disciplines use modularity to make interacting systems interchangeable and to insulate one system from another. Engineered biological systems are more likely to work as predicted if system function is decoupled from the state of the host cell. Also, specifying and standardizing the interfaces between a system and the chassis will allow systems to be engineered independent of chassis and allow systems to be interchanged between different chassis. To this end, we have assembled orthogonal transcription and translation systems employing dedicated machinery, independent from the equivalent host cell machinery. In parallel, we are developing test systems and metrics to measure the interactions between an engineered system and its chassis. Lastly, we are exploring methods to``port'' a simple engineered system from a prokaryotic to a eukaryotic organism so that the system can function in both organisms. / Poster presented at the 2005 ICSB meeting, held at Harvard Medical School in Boston, MA.

As an emerging area, systems biology provides a new paradigm not only for studying the cellular organization and regulation, but also for investigating how the systemic behaviors emerge in biological systems. One of the main objectives of systems biology is to understand mechanism and principle of the strategy that is applied in the metabolic network response to the environment and resources availability. Mass spectrometry (MS) was employed as the high-throughput technique tools to collect reliable data to obtain a quantitative understanding of the regulation of metabolic network in different cases. A LC-MS based method was developed and optimized for the measurement of central carbon metabolites in Escherichia coli. It could avoid the leakage problem and the "false high level" caused by the metabolites excreted to the medium, and provides better coverage as well as more accurate quantitative results of intracellular metabolites from different conditions. The developed method was employed to investigate the metabolic response to the nutrition stress. Intracellular concentrations of central carbon metabolites were measured under different nutrition conditions. The FBP concentration revealed the carbon influx because it served as a sensor of glycolytic flux and the α-ketoglutarate served as a coordinator of carbon and nitrogen flux response to the nutrient availabilities. A scenario was made that cell coordinated the catabolic and anabolic metabolism under different conditions by α-ketoglutarate and cAMP signaling. The overflow metabolism of E. coli was studied. A robust linear relation between acetate excretion rate and growth rate was observed. Gene expression level and quantitative proteomics approach were employed under perturbations such as mutants and increased energy demand (drained the energy by DNP). Acetate overflow in E. coli results from the tradeoff between efficient utilization of carbon resources by respiration and efficient utilization of proteome resources by fermentation. The physiology-driven approach was employed to investigate the potential targets of sRNA RyhB and the function of chaperon Hfq. Construction of a truncated RyhB mutant (RyhBt) was performed to confirm the necessity of hfq to RyhB. The expression of RyhB and RyhBt can both slow the growth rate. However, after the deletion of hfq, the growth defects induced by RyhB disappeared but still existed in the RyhBt strain without Hfq. It indicated that RyhB played its function by binding with Hfq at the special regions. Proteomics approach discovered some target genes of RyhB and RyhBt in both TCA cycle and nitrogen assimilation pathway. The relative abundance of proteins reflected that the RyhB and RyhBt affected the target differently because they had different binding sites with chaperons or targets. It will provided valuable information for revealing the inner mechanism of the physiology changes caused by sRNAs. GC-MS method was developed to identify and quantify the metabolites in E.coli cells. Three different derivatization methods for GC-MS were compared and optimized. The pool size of glutamine and glutamate was stable in the wild type strain at certain conditions but changed significantly in the GOGAT- strain especially the nitrogen was limited.

Circadian rhythms exist in almost all of living species, and they occupy an important role in daily biological activities of these species. This thesis deals with reduction of measurements in circadian models, and recovery of circadian phases. Two mathematical models of circadian rhythms are considered, with a 3rd order model for Neurospora, and a 7th order model for Mammals. The reduction of measurements of circadian models is shown by the proposals of observer designs to the two mathematical models of circadian rhythms. Both mathematical models contain strong nonlinearities, which make the observer design challenging. Two observer designs, reduced-order and one-sided Lipschitz, are applied to the circadian models to tackle the nonlinearities. Reduced-order observer design is based on a state transformation to make certain nonlinearities have no impact on the observer errors, and the design of one-sided Lipschitz observer is based on systems with one-sided Lipschitz nonlinearities. Both observer designs are based on the existing methods in literature. The existing method of reduced-order observer has been applied to a class of multi-output nonlinear systems. A new reduced-order observer design which extends the existing one in literature is presented in this thesis. In this new reduced-order observer method, the observer error dynamics can be designed by choosing the observer gain, unlike the existing one, of which the observer error dynamics depend on the invariant zeros under certain input-output map. The recovery of circadian phases is carried out to provide a solution to phase shifts occurred in circadian disorders. The restoration of circadian phases is performed by the synchronizations of trajectories of a controlled model with trajectories of a reference model. The reference model and the controlled model have phase differences, and both these models are based on a given 3rd order model of Neurospora circadian rhythms. The phase differences are reflected by different initial conditions, and by parameter uncertainty. The synchronizations of the two models are performed by using back-stepping method for the case of different initial conditions, and by using adaptive back-stepping method for the remaining case. Several simulation studies of the proposed observer designs and the proposed schemes of synchronizations are carried out with the results shown in this thesis.

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