Integration of Substrate Oxidation with Protein Synthesis and Cellular Signaling in a Complex Biological System
EMSL Project ID
48606
Abstract
These investigations will explore the complex interactions involved in cellular metabolism, protein synthesis, and cell signaling. We will use complex models to link intra-cellular regulatory networks that control the response of cells to their environment. First, we will perform studies on the neonatal pig heart and brain in vivo. The neonatal heart in particular provides an excellent model for all cell systems as it undergoes rapid growth through cell proliferation and expansion and adapts to quickly to physiological changes. The neonatal brain is also undergoing rapid development but is extremely vulnerable to insults. Secondly, we will explore the interactions between cellular metabolism and protein posttranslational modifications by O-GlcNAc in stressed hearts. Emerging evidence shows that cellular metabolism can directly affect cellular function by providing substrate for O-GlcNAc protein modifications. This aim includes the development of cutting edge techniques to identify and quantify O-GlcNAc modified proteins in the heart. These studies will have broad applications to protein synthesis, cellular signaling and metabolomics extending past our mammalian heart model. Regulation of these pathways is relatively conserved through evolution. Therefore, the defined principles and techniques will be applicable to metabolomics, protein synthesis and cellular signaling in microbes with specific EMSL interest.
Project Details
Start Date
2014-11-13
End Date
2015-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Co-Investigator(s)
Team Members
Related Publications
Kajimoto M., D.R. Ledee, A. Olson, N.G. Isern, I. Robillard Frayne, C. Des Rosiers, and M.A. Portman. 2016. "Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion." Journal of Cerebral Blood Flow and Metabolism 36, no. 11:1992-2004. PNNL-SA-118083. doi:10.1177/0271678X16666846