Kinetic modeling of complex biological systems
Ph.D. Student: Rob Leighty
Metabolic flux analysis (MFA) based on stable-isotope labeling experiments is an important quantitative method to assess metabolic control within biological networks. A precondition of current flux analysis methods is metabolic steady state, that is, all fluxes must be constant over the course of the tracer experiment. Although experiments can be set up to meet this requirement, continuously changing environments are a biological reality. Another restriction of the available tools is that the evaluated metabolic fluxes remain disconnected from enzyme kinetics. Therefore, development of methods for dynamic flux analysis is an obvious necessity. The goal of this project is to fully develop dynamic metabolic flux analysis (DMFA) as the unifying theory linking short time-scale kinetic studies and long time-scale monitoring of cellular physiology.
Specific aims of this research are: (i) develop efficient algorithms for simulating metabolic and isotopic dynamics in complex biological networks and quantifying kinetic control; (ii) apply these methods in combination with high-throughput genomic and proteomic techniques to monitor changes in physiology during fed-batch fermentation, and during cell differentiation; (iii) perform short time-scale perturbation studies to elucidate kinetic control of metabolic pathways in model organisms used for biofuels production.
Young JD, Walther JL, Antoniewicz MR, Yoo H, Stephanopoulos G.