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).