Biomedical Engineering Reference
In-Depth Information
1.
INTRODUCTION
:
MOLECULAR BIOLOGY AND
COMPLEX SYSTEM SCIENCES
A major goal of the study of complex systems is to formally describe and
understand how a large number of different
parts
interact and "self-organize"
into a
whole system
that exhibits properties that cannot be understood by study-
ing the components in isolation (2). This goal transcends various levels of de-
scription and is of particular importance in biomedical research because higher
organisms extend over multiple levels of organization. They are hierarchical
systems that integrate their smallest constituent parts—individual molecules
including DNA, proteins, and lipids—across multiple levels of organization, to
organelles, cells, tissues, organs, and the organism (Figure 1). Thus, in order to
understand the whole living system at the "macro" level in terms of molecular
parts of the "micro" level, it is necessary to traverse multiple levels of descrip-
tion and size scales through many iterations of integration.
The advent of recombinant DNA technology, almost four decades ago, and
the concomitant progress in protein biochemistry have led to great advances in
our understanding of the lowest level of organization, the genes and molecular
parts that comprise living systems. Analysis of how these components interact
has led to elucidation of the fundamental principles of living cells, such as the
genetic code, the transcription of genes into mRNA, and the translation of
mRNA into proteins. Since then the unfathomable complexity of other molecu-
lar processes of living systems, such as the cell's growth cycle and regulation of
its behavior by external signals, has attracted most attention in biology. Most
molecular biologists now almost entirely focus their efforts on the identification
of new genes and proteins and the characterization of their role in these proc-
esses.
However, it has recently become clear that, rather than studying individual
proteins and pathways separately, an integrative approach is necessary. This is
reflected in the burgeoning area of "Systems Biology," which seeks not only to
systematically characterize and categorize all the molecular parts of living or-
ganisms using massively parallel analytic techniques, but also to understand the
functional interactions between the molecules using computational approaches.
However, despite these efforts, most researchers use the new high-throughput
technologies of genomics simply to accelerate, and expand to the genome-scale,
the discovery of new molecular pathways. In contrast, the importance of vertical
integration across different levels of organization is still largely neglected.
Moreover, in molecular as well as systems biology, it is still often assumed
that the ability to describe mechanistic details through experimentation or the
use of mathematical models is equivalent to "understanding" the behavior of a
complex system. For instance, a cell is typically thought to enter cell division
because a growth factor binds to a cell surface receptor, activates a biochemical
cascade (e.g., ras-raf-MEK-Erk), and triggers expression of the protein
