The overall goal of the Systems Biology Core (Core B) is to provide experience, training and facilities for high-throughput measurements, together with expertise in bioinformatics and systems analysis in order to help the project investigators of the PPG to generate and test new hypotheses on systems-level mechanisms of short- and long-term hypoxia tolerance and susceptibility. Specifically, Core B will provide expertise and resources to: (a) acquire and analyze high-throughput data in humans, mice and flies on gene expression and genetic sequence variations in the context of hypoxia and the signaling pathways of interest; (b)acquire and analyze metabolic profiles and activity under normal and hypoxic conditions by NMR metabolomics, metabolic network reconstruction, and computational modeling;(c) to perform specific phenotypic measurements in flies and mice and develop computational models of physiological dynamics; and (d) deployment and curation of a physiological database and a web site and web-based tools for timely dissemination of data and findings. Core B will bring expertise in microarrays and pathway analysis, metabolic biochemistry and metabolomics, bioengineering and systems biology to work with all three projects and Core C in a variety of measurements and data analysis. In addition. Core B will be responsible for the web-based deployment and maintenance of data dissemination resources for the program project.

Public Health Relevance

In the proposed PPG, the participating research projects will study adaptive mechanisms to hypoxia in cardiovascular and central nervous systems with the goal of identifying molecular signatures of hypoxia tolerance and susceptibility that will be relevant and useful clinically. The core will assist in these goals by providing systems biology tools and expertise to help the project to analyze gene expression, identify signaling pathways, determine molecular signatures and understand integrative mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL098053-03
Application #
8376860
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$413,898
Indirect Cost
$132,639
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Zanon, Alessandra; Kalvakuri, Sreehari; Rakovic, Aleksandar et al. (2017) SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila. Hum Mol Genet 26:2412-2425
Zarndt, Rachel; Walls, Stanley M; Ocorr, Karen et al. (2017) Reduced Cardiac Calcineurin Expression Mimics Long-Term Hypoxia-Induced Heart Defects in Drosophila. Circ Cardiovasc Genet 10:
Azad, Priti; Zhao, Huiwen W; Cabrales, Pedro J et al. (2016) Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge's disease. J Exp Med 213:2729-2744
Gan, Zhuohui; Fu, Zhenxing; Stowe, Jennifer C et al. (2016) A Protocol to Collect Specific Mouse Skeletal Muscles for Metabolomics Studies. Methods Mol Biol 1375:169-79
Hartley, Paul S; Motamedchaboki, Khatereh; Bodmer, Rolf et al. (2016) SPARC-Dependent Cardiomyopathy in Drosophila. Circ Cardiovasc Genet 9:119-29
Pamenter, Mathhew E; Powell, Frank L (2016) Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis. Compr Physiol 6:1345-85
Dewan, Sukriti; McCabe, Kimberly J; Regnier, Michael et al. (2016) Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation-An Integrated Multiscale Modeling Study. J Phys Chem B 120:8264-75
Díaz-Trelles, Ramón; Scimia, Maria Cecilia; Bushway, Paul et al. (2016) Notch-independent RBPJ controls angiogenesis in the adult heart. Nat Commun 7:12088
Song, Shanshan; Jacobson, Krista N; McDermott, Kimberly M et al. (2016) ATP promotes cell survival via regulation of cytosolic [Ca2+] and Bcl-2/Bax ratio in lung cancer cells. Am J Physiol Cell Physiol 310:C99-114
Basaran, Kemal Erdem; Villongco, Michael; Ho, Baran et al. (2016) Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans. PLoS One 11:e0146087

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