Biology is moving from describing phenomena to understanding the design principles and dynamic operation of cellular modules, entire cells, and even organisms. This new approach, which has been termed systems biology, aims to holistically understand biological processes by employing mathematical analysis and computational tools to integrate the information content obtained in experimental biology and engineering.
In this project, experimental and theoretical studies will be integrated to achieve a better understanding of the dynamic operation of glucose repression signalling pathways in yeast for design of glucose de-repressed strains. Such strains are industrially attractive as cell factories for improving baker's yeast production from molasses, bioethanol production for sugar mixtures, and heterologous protein therapeutic production. Moreover, since glucose repression in yeast serves as a model for nutrient sensing in eukaryotic cells, the development of algorithms for this system may be applied to mapping of signa transduction pathways in higher eukaryotes - including humans.
This will ultimately facilitate drug discovery and drug target identification for complex diseases. To achieve this goal, genome-scale models will be combined with DNA array and metabolite profiling data of several glucose repression mutants. Detailed characterization of these mutants by model guided analysis of global cellular function will allow mapping of all pleotrophic effects, identification of co-regulated metabolic patterns, and subsequent engineering of the desired strains. This study will have a broad impact on the field of systems biology and yeast physiology/genetics.
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