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STRUCTURAL COMPONENTS
Administrative Core
In consultation with the Advisory Committee, the Center is governed by the
Executive Committee, which will administer all operational aspects of the
SPC, including all major scientific (phase-in, phase-out of projects, new
directions), fiscal (resource allocation, subcontracts, salary review of
Center personnel) and strategic (industrial relations, commercialization of
Center IP, IP management, release of data) decisions. Initially, Ruedi
Aebersold and Elaine Raines will constitute the Executive
Committee. The Advisory Committee will consist of local and national experts whose
advice will be sought on an ongoing basis.
Executive Committe Profiles
High Throughput Facility Working Group
The objective of the HTPF working group is the maintenance and operation
of the current ISB HTPF, the implementation of new technologies developed as
technology modules of SPC or from other sources, and provision of an
efficient interface with the applied project of the BWGs. The modular nature
of the technology development program will allow the continuous updating of
the HTPF without major interruptions and incompatibilities. The HTPF group is
an interdisciplinary team of researchers at the ISB. In addition to their
stated roles, they educate colleagues at the ISB through a one-on-one project
management strategy where each biological project is 'hosted' by one of the
HTPF personnel who acquires and interprets data and through host non-ISB
scientist for training in the facility.
HTPF Staff
Proteome Technology Research Group
This group constitutes the heart of the SPC. Its activities will focus on
the development and the integration of specific "technology modules" into
high throughput platforms. Each platform will be designed to perform a
specific type of proteomic measurement, i.e., represent a particular
proteome-wide biological assay. This research will be carried out in the
highly interactive, interdisciplinary research environment of the Institute
for Systems Biology (ISB) in which scientists with backgrounds in biology,
chemistry, engineering, computer science, mathematics and physics
collaborate.
Technology Transfer/Dissemination
In addition to dissemination through applied projects that are part of the
Biology Working Groups, technologies developed in the Center will be
disseminated through technology transfer, training and commercialization. SPC
will train personnel from academic or private sector research institutions in
emerging proteome technologies through regular courses, talks and seminars
and a visiting scientist program. The Center will further disseminate new
technology by commercialization through licensing partnerships with private
sector partners and transfer emerging Center technologies to the main
research institutions in the Puget Sound area, the University of Washington
(UW), the Fred Hutchinson Cancer Research Center (FHCRC), and the Seattle
Biomedical Research Institute (SBRI).
Biology Working Groups
Three biology working groups (BWG) will address key questions of
contemporary heart, blood and lung research and provide the interface between
the technology development and applied activities of the Center. The groups
bring together distinguished researchers in the Puget Sound area with the
purpose of identifying novel approaches to address biological problems
utilizing proteomics. The focuses of the three working groups are:
Macrophage activation. This group recognizes the critical
protective role played by monocyte/macrophage as a primary means of defense
in an inflammatory response through its capacity as the scavenger cell of the
body and its fundamental importance in specific immunity. However,
inflammation also forms the basis of a series of life-threatening and
functionally crippling diseases that includes atherosclerosis and fibrotic
lung diseases. In particular, the activated macrophage can release an
incredible array of proteins that can induce tissue damage, promote the
influx of more leukocytes and cause extensive scarring and fibrosis that can
result in occlusion of blood vessels and lung alveoli. Although a number of
checks and balances prevent this destructive potential from being realized in
normal responses to injury, they are insufficient to block the progressive
destruction in chronic inflammatory diseases. Thus, defining the
comprehensive proteome of an activated macrophage is of primary importance to
identify strategies to regulate the destructive pathways without
significantly impairing protective mechanisms.
Cardiovascular and blood cell development. This group is based
on the insight that different cells in an organism are defined by the
complement of genes that they express. Cell fate choices reflect and require
the initiation of new programs of gene expression (and extinguishing of
others) that once initiated, must be faithfully passed from parental cells to
their progeny. Therefore, to appreciate the complex processes of mammalian
development and potentially apply this knowledge to gene therapy for genetic
disorders, it is essential to understand how a cell determines which genes it
will express. A major unresolved question is how these changes are initiated
and propagated at specific gene loci during development. The goal of this
area of investigation is to use mass spectrometry to interrogate these
changes during the differentiation of specific cardiac and hematopoietic cell
lineages. The development of technological approaches and general models
established from these studies should provide a basis for studying
tissue-specific gene expression at multiple loci, including those of the
macrophage that is the long-term focus of this program.
Signaling. The Signaling Working Group recognizes that changes
in signaling pathways and the composition of signaling complexes are critical
to the initiation of contraction, proliferation, activation, and
apoptosis ? processes involved in a variety of cardiovascular
diseases. Many of the same signaling pathways have been implicated in all of
these processes, and yet the stimuli and downstream effectors are distinct.
The proposed studies will focus on the signaling pathways in cardiac myocytes,
vascular smooth muscle, fibroblasts and endothelial cells whose signaling
pathways share many common themes. Hypothesis-driven analysis of signaling
complexes and more discovery-based approaches such as yeast two-hybrid
analysis have demonstrated that critical players in particular signaling
complexes interact directly with diverse groups of proteins, including
protein kinases, kinase anchoring proteins, scaffolding proteins and cell
adhesion molecules. However, definition of these complexes is far from
complete. Particular signaling pathways, such as those associated with
membranes, have been especially difficult to approach experimentally. The
goal of this working group is to try to expand our ability to probe signaling
pathways and complexes by using mass spectrometry to: 1) more completely
define the changes in cellular protein profiles associated with major
physiologic responses; 2) detail the components of specific signaling
complexes and determine how they dynamically change with different physiologic
stimuli; 3) determine the state of phosphorylation of signaling complexes and
changes in the protein phosphorylation profile of proteins in response to
physiologic stimuli; and 4) develop new approaches for examining protein
interactions in signaling pathways highly regulated by their membrane
interactions.
It should be noted that the projects of the BWGs are not directly funded
by the Center. The Center will, however, make capacity for sample processing
available via the HTPF.
BWG Staff
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