TITLE: Small Systems Biology

SPEAKER: Professor Eberhard O. Voit

ABSTRACT:

The combination of high-throughput methods of molecular biology with advanced mathematical and computational techniques has propelled the emergent field of systems biology into a position of prominence. Unthinkable only a decade ago, it has become possible to screen and analyze the expression of entire genomes, simultaneously assess large numbers of proteins and their prevalence, and characterize in detail the metabolic state of a cell population. While very important, the focus on comprehensive networks of biological components is only one side of systems biology. Complementing large-scale assessments, and sometimes at risk of being forgotten, are more subtle analyses that rationalize the design and functioning of biological modules in exquisite detail. This intricate side of systems biology aims at identifying the specific roles of processes and signals in smaller, fully regulated systems by computing what would happen if these signals were lacking or organized in a different fashion. I will exemplify this type of approach with two examples. The first is a detailed analysis of the regulation of glucose utilization in /Lactococcus lactis/. This organism is exposed to alternating periods of glucose availability and starvation. During starvation, it accumulates an intermediate of glycolysis, which allows it to take up glucose immediately upon availability. This notable accumulation poses a non-trivial control task that is solved with an unusual, yet ingeniously designed and timed feedforward activation system. The elucidation of this control system required high-precision /in vivo/ data on the dynamics of intracellular metabolite pools, combined with methods of nonlinear systems analysis, and may serve as a paradigm for multidisciplinary approaches to fine-scaled systems biology. The second example describes our attempts to understand signal transduction in the human brain, along with perturbations in diseases like Parkinson’s disease and Schizophrenia.


*/References:/*

Voit, E.O.: /Computational Analysis of Biochemical Systems. A Practical Guide for Biochemists and Molecular Biologists/, xii + 530 pp., Cambridge University Press, Cambridge, U.K., 2000.

Voit, E.O., A.R. Neves, and H. Santos. The Intricate Side of Systems Biology. /PNAS/, 103(25), 9452-9457, 2006.

Qi, Z., G. W. Miller, and E. O. Voit: Computational analysis of determinants of dopamine dysfunction. /Synapse/* 63*: 1133-1142, 2009.

Wu, Jialiang, Z. Qi, and E.O. Voit: Investigation of delays and noise in dopamine signaling with hybrid functional Petri nets. In Silico Biol. 10, 0005 (2010).