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The Heart Biology Core is
based on ongoing collaborative work among the Project Leaders and
will have the following individual components to ensure the support
and rapid advance of the projects: 1. High Resolution Confocal
Imaging (subcellular localization of mitochondrial signaling
molecules). 2. Mitochondrial Function (changes of mitochondrial
function and modulation by signaling cascades). 3. Systems Biology
(analysis of hemodynamics and cardiac function), and 4. Molecular
Genetics and Molecular Biology (transgenic animal models and viral
constructs for cardiomyocyte transfection). The Core will host the
following four functions:
First, the Heart Biology Core
will support maintenance and supervision of costly shared
instruments, including training of PPG members that will use the
Core instruments under the supervision of the responsible PPG member
(e.g. Mouse Physiology laboratory for ischemia/reperfusion injury
analysis; one and two photon laser-scanning confocal microscopy).
Second, the Heart Biology Core
will provide continuous service of standard procedures for daily use
of the Project Leaders. In this case, the Core will have personnel
in a dedicated space for the procedures. The personnel will be
responsible for this work and will provide daily service to all PPG
members (e.g. transgenic animal models and viral constructs for
cardiomyocyte transfection).
Third, the Heart Biology Core
will establish and develop sophisticated techniques and provide
assistance to the various Project Leaders to perform experiments
they cannot do in their own laboratories. In this case, the core has
the role to train members of the Project Leaders' laboratories in
the acquisition and analysis of the data. The Core member will
either directly perform the procedures or will supervise and discuss
the work done by members of the Project Leaders' laboratories (e.g.
analysis of mitochondria function and structure, including
experiments with isolated mitochondria or permeabilized
cardiomyocytes; high resolution laser confocal and two photon
microscopy).
Finally, the Heart Biology
Core will collaborate with the Proteomic Core and provide support on
target validation at the organelle and systems level. Studies to
identify and quantitate proteins and phosphorylation events
conducted by the Proteomic Core will generate lists of candidate
subproteome members that will require validation. The Heart Biology
Core will support the validation of these proteins with respect to
their mitochondrial compartmentalization and co-localization with
MPT pore components, their functional roles in mitochondrial
metabolism and MPT, and their affects to regulate cardiac function.
Findings from these studies will feed back to the bioinformatic
model of the signaling network in the Proteomic Core and will
suggest further subproteome mapping studies on the basis of
functional data. The robust interactions between the Heart Biology
and Proteomic Cores will facilitate the progression of the Aims of
the individual Projects and will support the overall goal of the PPG
to link subproteome analyses to organelle, cell and systems
phenotype.
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