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School of Chemical Engineering,
Purdue University
Date: October 13, 2009
Time: 4:00 p.m.
Location: ESB 1001
Metabolic networks feature a multitude of chemical reactions involving uptake of external nutrients and transforming them to various intracellular metabolites, fermentation products which are released into the surrounding medium, and biomass. These reactions are catalyzed by highly specific enzymes whose levels and activities are subject to control within a metabolic regulatory system dictated by the genomic background of the organism. Dynamic modeling of metabolic systems is essential to develop quantitative understanding of biological systems and to facilitate design, optimization and control of biotechnological processes.
While the methodology of chemical reaction engineering with its armory of stoichiometry, kinetics, transport and thermodynamics uniquely befits the analysis of metabolic networks, the complexity of regulatory processes has challenged dynamic modeling of metabolism. Consequently, steady or quasi-steady state methods have prevailed with their limited capacity to be predictive as they seek to incorporate regulatory effects through measured fluxes.
This presentation will discuss dynamic modeling of metabolic systems from our cybernetic approach that is based on viewing regulatory processes as being inspired by survival of one form or another. It postulates optimal investment of the organism’s resources for selective synthesis of enzymes that will drive reactions favoring the organism’s survival. The theory features the usual concentration variables associated with reaction kinetics as well as cybernetic variables that are control variables shown to depend only on reaction kinetics from optimal control theory. These control variables concern both enzyme syntheses and enzyme activities.
In applying the foregoing ideas to metabolic networks, we draw on the concept of elementary modes, which represent a convex basis for the null space of the metabolic stoichiometric matrix. Elementary modes are viewed as pathway options for metabolic function by which the organism manipulates its response to its environment so that survival is promoted one way or another. The approach reveals metabolic systems as a hotbed of nonlinear phenomena with hysteresis, steady state multiplicities and complex oscillatory transients.
Successful applications of cybernetic models to metabolism of bacteria and yeast are presented. The cybernetic models represent the most promising tool for metabolic engineering as they have a means to account for metabolic burden imposed by pathway changes. Thus they make available a mechanism for any effect that a specific change in the pathway may have on reactions in the network far removed.
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Biographical Sketch - Doraiswami Ramkrishna
Dr. Doraiswami Ramkrishna is an H.C. Peffer Distinguished Professor of Chemical Engineering at Purdue University since 1994. Since receiving his B.(Chem).Eng. from the University of Bombay in 1960, he obtained his PhD from the University of Minnesota in 1965. After two years of being an Assistant Professor at the University of Minnesota, he joined the faculty at the Indian Institute of Technology at Kanpur, India where he served until 1974. Following two years of visiting appointments at the Universities of Wisconsin and Minnesota, he joined as a Full Professor of Chemical Engineering at Purdue University in 1976.
Dr. Ramkrishna’s research interests are in the application of mathematics to chemical and biochemical reaction engineering, particulate processes and biomedical engineering His research in the biological area encompasses applications of population balances, cybernetic modeling of metabolic systems, metabolic engineering, and modeling of cancer therapy. He has published over 200 papers, two books, and directed close to 40 PhDs and numerous post-docs.
He has won awards from the AIChE: Alpha Chi Sigma (1987), Wilhelm Reaction Engineering (1998) and Thomas Baron (2004). From elsewhere: Germany: the Senior Humboldt (2000), India: UDCT Diamond Award (1994) and Platinum Award (2009) from Bombay University. Fellows of Professional Societies, AIMBE (1996), IIChE (Honorary; 2001), AIChE (2007), Honorary Doctor of Science from the University of Minnesota in 2004, He has held Distinguished Visiting Professorships at the University of Minnesota (George T. Piercy: Fall 1988) and at the University of Notre Dame (Melchor; Fall 1994) and given numerous distinguished lectures. He was elected to the NAE in 2009.
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