Monday, February 6th, 2012
9:30am - 10:30am, in McCormack 2-145

Kourosh Zarringhalam

Boston College

Mathematical determination of metabolic remodeling specificities of choline and ethanolamine glycerophospholipids

Abstract: The regulation and maintenance of the cellular lipidome through biosynthetic, remodeling, and catabolic mechanisms are critical for biological homeostasis during development, health and disease. These complex mechanisms control the molecular architectures of lipid molecular species, which have diverse yet highly regulated fatty acid chains at both the sn1 and sn2 positions. Here we present a mathematical dissection of the mechanisms influencing phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecular architectures and remodeling from high-throughput shotgun lipidomic data. Using a novel statistical approach based on Fisher's exact test and Markov Chain Monte Carlo sampling, we first determine the degree of association among the chain types at the sn1 and sn2 positions in PC and PE. We then use the inferred associations to describe the dynamical system of ODE that govern the kinetic reactions in the remodeling pathway. We reduce the complexity of the dynamical system and infer the unknown kinetic parameters using a novel optimization technique and a network inference algorithm. Simulations show that our model is in close agreement with experimental data.