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Synthetic biologists seek to engineer
novel cellular functions that have a broad range of useful applications, such
as the treatment of human disease or the creation of a renewable energy source. In
order for engineered systems to behave predictably and specifically,
the
constituent components must be very well
characterized,
and such detailed knowledge is often lacking. Furthermore, it is
unclear how
effectively even well-understood parts can be combined into more
sophisticated
networks. These challenges are particularly acute in eukaryotic
systems, which
themselves are highly complex. With these scientific issues in mind, I
have concentrated on the role of transcriptional regulation in
synthetic networks in the
budding yeast Saccharomyces cerevisiae.

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Specifically, I have engineered a panel of novel
artificial transcription factors (see cartoon on left), quantitatively characterized their ability to
regulate gene expression, and re-configured a subset of these networks to build
a synthetic in vivo memory device. In
addition to these significant technological advances, I have addressed the degree to
which the behavior of synthetic networks can be predicted from comprehensive
characterization of the individual components. Thus, this work
provides a foundation for building transcriptional networks with variety of
topologies and functionalities in S.
cerevisiae. |
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