lee pang - Academia.edu (original) (raw)
Papers by lee pang
Molecular Systems Biology, 2010
Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nu... more Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations-this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of c rays.
Nature, 2008
We monitor the response of S. cerevisiae metabolic gene regulation to periodic changes in the ext... more We monitor the response of S. cerevisiae metabolic gene regulation to periodic changes in the external carbon source. We find that the system acts as a low-pass filter that reliably responds to a slowly changing environment, while effectively ignoring fluctuations that are too fast for the cell to efficiently respond. We use computational modeling to determine that frequency selection in the system is controlled by the interaction of coupled positive feedback networks governing the signal transduction of alternative carbon sources. Our findings establish a framework for probing organisms to reveal the mechanisms that mediate cellular responses to unpredictable environments.
Molecular Systems Biology, 2005
Recent progress in reconstructing gene regulatory networks has established a framework for a quan... more Recent progress in reconstructing gene regulatory networks has established a framework for a quantitative description of the dynamics of many important cellular processes. Such a description will require novel experimental techniques that enable the generation of time-series data for the governing regulatory proteins in a large number of individual living cells. Here, we utilize microfabrication to construct a Tesla microchemostat
Molecular Systems Biology, 2010
Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nu... more Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations-this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of c rays.
Nature, 2008
We monitor the response of S. cerevisiae metabolic gene regulation to periodic changes in the ext... more We monitor the response of S. cerevisiae metabolic gene regulation to periodic changes in the external carbon source. We find that the system acts as a low-pass filter that reliably responds to a slowly changing environment, while effectively ignoring fluctuations that are too fast for the cell to efficiently respond. We use computational modeling to determine that frequency selection in the system is controlled by the interaction of coupled positive feedback networks governing the signal transduction of alternative carbon sources. Our findings establish a framework for probing organisms to reveal the mechanisms that mediate cellular responses to unpredictable environments.
Molecular Systems Biology, 2005
Recent progress in reconstructing gene regulatory networks has established a framework for a quan... more Recent progress in reconstructing gene regulatory networks has established a framework for a quantitative description of the dynamics of many important cellular processes. Such a description will require novel experimental techniques that enable the generation of time-series data for the governing regulatory proteins in a large number of individual living cells. Here, we utilize microfabrication to construct a Tesla microchemostat