gene at a time research towards
network biology. These network
biology methods include genetic
interaction networks (e.g. QTL
genetics, see work from Vivian
Cheung or Eric Schadt), physical
interaction networks (e.g. protein
protein interaction, see work from
Marc Vidal or Mark Gerstein), gene
regulatory networks (e.g. RNA
expression and ChIP-seq methods, see
work from Klaus Kaestner, Rick
Young, Bing Ren), and many others.
These approaches have not only
identified causal relationships between
gene networks and physiology and
behavior, but also captured these
fashion rather than through the lens
of a "master gene". (These master
genes exist, but a consequence of
their celebration in the literature and
through their funding in NIH grants
is that more than half of the human
genome goes unstudied (Su and
Hogenesch, 2007).)
done at a static time point. As Einstein
or my two-year-olds would attest,
most interesting things happen when
something moves. Objects at rest tend
to stay at rest (and boring). Over the
past several years, our lab has been
developing methods to perturb
analytical biochemistry coupled with the
development of high accuracy mass
spectrometers have uncovered and in part
quantified tissue and cellular proteomes.
While these technological advances have
enabled the undertaking of broad, global,
ambitious projects, have also challenged us to
creatively use these inventories to construct
and advance novel biological paradigms. As
such we consider proteomics as a continuum
of activities that has permitted investigations
on the structural elements that govern the
formation and function of post-translational
modifications mediated by nitric oxide (1, 2).
Furthermore, within this continuum, we
used functional proteomics to discover
proteins secreted by astrocytes that
independently or interactively modulate
physiological and pathological responses in
the central nervous system (3, 4). Below I
briefly describe these two areas of
investigation that define the core
commitments of recent efforts in the
laboratory.
Dennis Alter Research Professor of Pediatrics
and Pharmacology