Validating mathematical models of the yeast sterol regulatory pathway.
Disorders in human cholesterol regulation can lead to heart disease, the leading cause of death in the United States. We seek to understand the cholesterol regulatory system better by studying the homologous system in fission yeast (Schizosaccharomyces pombe). Using biochemical experiments – done in collaboration with Peter Espenshade of the Department of Cell Biology, JH School of Medicine, and principles from control engineering and dynamical system theory, we are developing, analyzing and validating mathematical models 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.
Some publications related to this work are:
1. Porter JR, Burg JS, Espenshade PJ, Iglesias PA. Identifying a static nonlinear structure in a biological system using noisy, sparse data. J Theor Biol. 300:232-41, 2012.
2. Porter JR, Lee CY, Espenshade PJ, Iglesias PA. Regulation of SREBP during hypoxia requires Ofd1-mediated control of both DNA binding and degradation. Mol Biol Cell. 23:3764-74, 2012.
3. Porter JR, Burg JS, Espenshade PJ, Iglesias PA. Ergosterol regulates sterol regulatory element binding protein (SREBP) cleavage in fission yeast. J Biol Chem. 285:41051-61, 2010.