Biology Reference
In-Depth Information
a catalogue. The protein species contained in a cell under certain conditions
could thus be made visible as soon as protein analytical methods allowed for
high enough resolution. In a sense, then, proteomics began with the first series
of experiments that could resolve most of the proteins of a cell, presented
by Patrick O'Farrell in a seminal methodological paper on two-dimensional
gel electrophoresis of proteins. He resolved 1100 proteins from
E. coli
and
estimated a maximal resolution of the method of 5000 proteins (O'Farrell,
1975). His method allows to detect many mutations and, of course, changes
in the protein expression pattern. Less resolution was needed initially in the
analysis of the proteomic subset of heat shock proteins in
Drosophila
, in which
early genomic and proteomic data were already combined (Tissières et al.,
1974; Ashburner & Bonner, 1979). However, this 'early proteomic project'
was not primarily interested in the dynamics of a proteomic network as is
systems biology. The structural data that could be obtained were mainly used
within the framework of analysis of already known functions of individual
proteins.
6. THE BRANCHES OF SYSTEMS BIOLOGY: MERGERS OF THE
DIFFERENT ROOTS
Systems biology aims to model biological systems in ways that combine aspects
that we have addressed in the discussion of its three roots: (i) detailed models of
genetic and metabolic networks that are built from molecular components in the
tradition of bottom-up pathway modeling; (ii) models that describe the overall
dynamics of large networks and divide large (sometimes cell-encompassing)
networks into modules (nearly separable regulatory subunits), a modeling strat-
egy related to cybernetic top-down modeling; and (iii) grounding of many of
its models in 'omic' data sets, which is clearly the case with the top-down
approach, but to some extent also with cases from the bottom-up tradition. The
availability of high-throughput methods and the 'omic' data sets gathered by
using them can be seen as crucial for the transformation of pathway modeling
and biological cybernetics into systems biology. The new richness of structural
data allowed the refinement of models that were based on kinetic data of only
a few components, leading to detailed models of the dynamics of complex
networks.
6.1. The first branch of systems biology: Detailed bottom-up
regulatory models
A fairly continuous development leads from the tradition of modeling regulatory
networks to more recent models of similar networks that run under the unifying
