Bringing Computers Into Biology
Image: Adapted with permission from
AJP - Cell Physiol
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The explosion of data from
gene sequencing projects has left biologists scrambling to make
sense of it all. Help comes from the field of bioinformatics, whose
scientists organize and examine masses of data to reveal and extract
new information.
Other scientists explore the vast, intertwined
networks of factors that sculpt the behavior of whole cells, tissues,
or organisms. These complex studies overwhelm traditional"reductionist"
techniques that hammer out the roles of individual molecules. The
solution is to use an entirely new method — computer modeling,
which harnesses approaches from computer science, math, physics,
and engineering.
To support such computer-based strategies, NIGMS
launched its newest component, the Center for Bioinformatics and
Computational Biology (CBCB). This Center supports theoretical and
quantitative studies of biological networks and dynamic processes.
Fields that already have a strong quantitative
backbone — such as population biology, biophysics, biophysical
chemistry, structural biology, and drug design — are supported
within the NIGMS scientific divisions. The new Center focuses instead
on recruiting investigators with mathematical and computational
expertise to study processes like cell division, cell motility and
mechanics, the assembly and dynamics of macromolecular complexes,
signal transduction, metabolism, gene expression, and pattern formation
in embryogenesis.
The Center supports multidisciplinary collaborations,
sponsors workshops and meetings, defines the Institute's needs for
database development and applications, and collaborates with other
NIH components and Federal agencies in developing policies in this
area.
Mining and Modeling Biology's Complexities
The research supported by CBCB focuses on a wide
variety of systems, organisms, and biological processes. One example
is work led by Douglas Lauffenburger of the Massachusetts Institute
of Technology. His research team borrows an approach from electrical
engineering to examine how a cell's behavior is governed by biochemical
reactions on its surface. Using a signal processing circuit model,
the scientists are able to explain, predict, and intentionally alter
the behavior of cells.
Another
researcher, Garrett Odell of the University of Washington, uses
computer simulation to study the molecular gymnastics required for
cells to move and change shape. His group focuses on protein molecules
called actin and tubulin that assemble into long filaments, and
myosin molecules, which chug like railcars along actin filaments.
The team's goal is to understand how all these
molecules work together to mold cells into tissues in developing
embryos. Because errors in early development underlie a variety
of cancers and birth defects, understanding molecular details of
the process may help treat or prevent these disorders.
Physicist Stanislas Leibler of Rockefeller University
seeks to capture mathematically how myriad factors, including genes,
interacting molecules, and environmental signals, weave together
to control a cell's behavior. He and his collaborators focus on
how bacteria respond to chemical changes in their environment —
a process called bacterial chemotaxis that allows the bacteria to
move toward food and away from noxious chemicals. Their models are
designed to predict the bacteria's behavior under different conditions.
To complement and refine this theoretical approach, they conduct
laboratory experiments in which they alter the internal biochemistry
of E. coli bacteria and examine how these changes affect
the speed or accuracy of the bacteria's movement. Surprisingly,
even genetically identical bacteria behave very differently. Leiber's
group seeks to figure out why.
The researchers expect that their studies will
reveal the connections between, and relative influence of, the network
of factors that control bacterial chemotaxis. These "design
principles" will in turn advance our understanding of many
other biological signaling pathways.
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