Modeling Sterol Regulatory System
Disorders in human cholesterol regulation can lead to heart disease, the leading cause of death in the United States. We seek to better understand the cholesterol regulatory system by studying the homologous system in fission yeast (Schizosaccharomyces pombe). Using biochemical experiments and the principles of control engineering and dynamical system theory, we are developing, analyzing, and validating a mathematical model of the yeast sterol regulatory pathway. Our goal is to understand how the components of this pathway work together to achieve several performance objectives, including the maintenance of sterol levels under changing environmental conditions. We expect that this knowledge will lead to improvements in the treatment of cholesterol-related human diseases.
Sre1 (X) binds to Scp1 (W) to form a complex (Y). Blockage of the sterol production pathway (A-Q-N-L-S) leads to this complex being transported from the ER to the Golgi, cleaved, and transported to the nucleus (XN). XN serves as a transcription factor for enzymes (E) that restore flux through the sterol production pathway. At high levels of oxygen (U), XN levels are kept low through degradation mediated by Ofd1 (F).
Disorders in human cholesterol regulation can lead to heart disease, the leading cause of death in the United States. We seek to better understand the cholesterol regulatory system by studying the homologous system in fission yeast (Schizosaccharomyces pombe). Using biochemical experiments and the principles of control engineering and dynamical system theory, we are developing, analyzing, and validating a mathematical model of the yeast sterol regulatory pathway. Our goal is to understand how the components of this pathway work together to achieve several performance objectives, including the maintenance of sterol levels under changing environmental conditions. We expect that this knowledge will lead to improvements in the treatment of cholesterol-related human diseases.
Sre1 (X) binds to Scp1 (W) to form a complex (Y). Blockage of the sterol production pathway (A-Q-N-L-S) leads to this complex being transported from the ER to the Golgi, cleaved, and transported to the nucleus (XN). XN serves as a transcription factor for enzymes (E) that restore flux through the sterol production pathway. At high levels of oxygen (U), XN levels are kept low through degradation mediated by Ofd1 (F).