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Synthetic gene oscillators and their applications

Abstract

Synthetic biology seeks to understand and engineer biological networks that perform a quantitative dynamic function in organisms. Since the original toggle switch (Gardner et al., 2000a) and oscillator designs (Elowitz and Leibler, 2000a), genetic circuits have been constructed that control cellular population growth (You et al., 2004b), detect edges in an image (Friedland et al., 2009), and count discrete cellular events (Friedland et al., 2009). In this thesis, we focus on synthetic gene circuits that produce oscillations. Oscillations are important in a vast range of natural contexts such as circadian rhythms, cardiac function, cell division, and hormonal regulation, as well as key to building synthetic control systems that rely on precise timing. Here we discuss modeling, designing, constructing, and characterizing synthetic gene oscillators. In Chapter One, we give an overview and introduction to the field of synthetic biology and how our research area fits into this discipline. In Chapter Two, I discuss a network design which produces synchronized oscillations in a growing population of cells. In Chapter Three, I discuss an introduction to modeling simple genetic networks. In Chapter Four, we look at a scenario where synthetic gene circuits that produce an overabundance of tagged components lead to unexpected correlations. In Chapter Five, I discuss modeling genetic networks and further go into detail about spatial modeling of networks that produce patterns in mammalian cells. These parts combine to illustrate how to design, model, construct, and characterize synthetic gene networks in bacteria and mammalian systems

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