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February 19, 2004
James C. Liao
Chemical Engineering Department University of California at Los Angeles 5531 Boelter Hall
Los Angeles, CA 90095
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"Intracellular Regulatory Networks"
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Abstract
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Self-regulation (or self-control) is one of the key features which distinguish biological reaction systems from others. The regulatory action is achieved through multiple levels of intracellular regulatory networks, which receive inputs from the environment and "compute" a proper output to guide cellular behavior. Our research focuses on two aspects of intracellular regulation: 1) deducing the genome-wide transcriptional regulatory networks from DNA microarray data, and 2) re-wiring gene-metabolic regulatory network for a desired purpose. The former sets the foundation for understanding intracellular regulation, whereas the latter aims to design novel gene-metabolic circuits. Using Bayesian statistics and a large amount of DNA microarray data, we developed methods for deducing the basic units of transcriptional regulation, namely operons and regulons. We further developed a method for reconstruction the dynamics of transcription regulator activities using network-enabled decomposition. We demonstrated the applicability of this approach to eukaryotes by determining the transcription factor activities during Saccharomyces cerevisiae cell cycle and by identifying the direction and magnitude of their regulatory effects on each gene.
Aided by the knowledge of transcriptional regulation and metabolism, we developed a strategy for building novel gene-metabolic circuits. The first example is the artificial transcriptional feedback regulation which directs the metabolic flux to a non-native pathway. This artificial regulatory loop senses intracellular states and use this signal for feedback control. A more complicated loop results in a coupled gene-metabolic oscillator, which is potentially synchronizable between cells and tunable by extracellular conditions. Finally, the application of these strategies on cell-based biosensing for space exploration will be discussed.
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Room: 1064 Duncan Hall . Time: 2:30 PM For more information contact: |
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