Introduction: Changes in protein expression and post-translational modifications (PTMs) are essential mechanisms for biological regulation in normal physiology and numerous diseases, including those of the cardiovascular disease [1-4]. Characterizing these changes can provide valuable information for the elucidation of disease etiology, identification of clinically useful biomarkers, and development of novel therapeutics. Thus, methods for the identification of proteins and characterization of protein PTMs are essential to modern biomedical research. In recent years, mass spectrometry (MS)-based proteomics has become the technology of choice for these purposes. MS-based proteomics takes advantage of the modern mass spectrometer's superior resolution power and accuracy in peptide sequencing [5]. It allows for the rapid, large-scale identification and quantification of proteins and their PTMs in multiprotein complexes, whole cells, tissues and organisms with sub-femto mole level sensitivity (100-1000 times more sensitive than traditional technologies). Recently, MS combined with stable isotope labeling technologies (i.e. quantitative proteomics) has emerged as a powerful tool to quantitatively assess dynamic changes in protein expression, subcellular compartmentalization and PTMs on a proteome-wide scale [6]. Therefore, MS-based proteomics is unequaled as a tool for studying complex biological systems and disease in the post-genomic era. All these various tools are particularly applicable to cardiovascular research and should allow us to carry out the goals of this PPG. The ability to deliver genes efficiently to cultured cardiomyocytes and in vivo to the rodent heart is critical to many of the experiments described in the three PPG projects. Viral vectors offer greater transduction efficiency to cultured cardiomyocytes than nonviral methodology such as plasmid DNA delivery via liposomal reagents, electroporation or nucleofector techniques [7]. Similarly, viral vectors are more efficient than non-viral gene delivery methods in mediating gene delivery in vivo to the heart [8]. The Viral Vector Core will provide adenoviral and adeno-associated viral vector development, manufacturing, purification, and validation services to this PPG.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL075443-07
Application #
8323339
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
7
Fiscal Year
2011
Total Cost
$462,052
Indirect Cost
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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