Biomedical Engineering Reference
In-Depth Information
population genetics approaches. More recently differential equation-based mod-
els for the dynamics of regulatory systems following structural perturbation have
also been explored (61).
3.2. Feedback Control
Elementary feedback control systems have three components: a plant (the
system under control), a sensor (measuring the output of the plant) and a con-
troller (generating the plants input) (12). A measure of performance is often the
degree to which the output of a plant approximates some function of the input to
the controller. In biology a plant could be RNA or protein concentration, protein
kinase activation, immune effector cell abundance, or species abundance. Inputs
in each of these cases would be transcription factors, protease concentrations,
chemical agonists bound to receptors, antigen concentrations, and death rates.
The controllers are more often than not aggregates of several mechanisms.
Feedback is a mechanism of robustness as it enables plants to operate efficiently
over a range of exogenous input values. The question remains as to whether the
controller is robust to variations in the plant—does it provide robust stability ?
For example, in biology, can a single feedback controller regulate the concentra-
tions of several different proteins?
The theoretical literature in linear feedback control is very well developed
in engineering. Biology has borrowed extensively from this literature. Nonlinear
feedback control is another issue, and there are few canonical models (1).
3.3. Modularity
Repeated representations of functionally distinct character complexes capa-
ble of recombination or shuffling is an example of modularity. Modularity aims
to capture structures that balance autonomy and integration. Within a complex
there is strong integration, whereas populations of complexes are only weakly
coupled (55). This has also been called near decomposability (54). In genetics,
modularity involves a minimum of pleiotropy, in which sets of genes contribut-
ing to one complex or trait (for example, organ system) make little contribution
to other complexes or traits (16,49,50). These modular genetic systems are
found in different genomic contexts performing a similar function. Of course,
modularity can be defined at levels of organization above that of the gene (64)—
e.g., the extent to which organs operate independently during homeostasis. The
dissociability of modules provides one means of damage limitation through en-
capsulation.
There are no collectively agreed upon models for analyzing modularity in
biosystems. To date quantitative genetics models have been used to explore the
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