This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Subcellular localization and translation of mRNAs provides cells with a locally renewable source of proteins to autonomously respond to extracellular stimuli. For neurons, this is critical since the cytoplasm and membranes of neurons can extend for several hundred times the dimensions of the cell body. Work in developing neurons has shown that localized protein synthesis plays a role in axonal pathfinding, provides structural protection to the axon, and triggers anterograde and retrograde axonal transport. Studies from the PI's group have shown that axonal protein synthesis is triggered by injury in adult neurons and that regenerating axons show particularly robust intra-axonal protein synthesis. This localized protein synthesis represents a mechanism that could be modulated to facilitate the regenerative capacity of axons in the adult nervous system. Despite the obvious functional significance of and newly increased interests in axonal protein synthesis, we know of excessively few mRNAs whose local translation is regulated by extracellular stimuli. Our preliminary studies indicate that adult axons have the potential to synthesize a complex population of more than 200 different proteins. We hypothesize that axonal stimulation alters localized protein synthesis through both directing the transport of particular mRNAs into the axonal compartment and locally controlling the activity of the axonal translational machinery. The objective of this BioAMS project is to use the high sensitivity of AMS for quantifying how protein synthesis is regulated in regenerating axons.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR013461-12
Application #
8171686
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Project Start
2010-06-01
Project End
2011-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
12
Fiscal Year
2010
Total Cost
$42,480
Indirect Cost
Name
Lawrence Livermore National Laboratory
Department
Biology
Type
Organized Research Units
DUNS #
827171463
City
Livermore
State
CA
Country
United States
Zip Code
94550
Sahoo, Pabitra K; Smith, Deanna S; Perrone-Bizzozero, Nora et al. (2018) Axonal mRNA transport and translation at a glance. J Cell Sci 131:
Wang, Zhican; Fang, Ying; Teague, Juli et al. (2017) In Vitro Metabolism of Oprozomib, an Oral Proteasome Inhibitor: Role of Epoxide Hydrolases and Cytochrome P450s. Drug Metab Dispos 45:712-720
Wan, Debin; Yang, Jun; Barnych, Bogdan et al. (2017) A new sensitive LC/MS/MS analysis of vitamin D metabolites using a click derivatization reagent, 2-nitrosopyridine. J Lipid Res 58:798-808
Zimmermann, Maike; Wang, Si-Si; Zhang, Hongyong et al. (2017) Microdose-Induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice. Mol Cancer Ther 16:376-387
Stornetta, Alessia; Zimmermann, Maike; Cimino, George D et al. (2017) DNA Adducts from Anticancer Drugs as Candidate Predictive Markers for Precision Medicine. Chem Res Toxicol 30:388-409
Wang, Si-Si; Zimmermann, Maike; Zhang, Hongyong et al. (2017) A diagnostic microdosing approach to investigate platinum sensitivity in non-small cell lung cancer. Int J Cancer 141:604-613
Kim, Jeffrey; Stewart, Benjamin; Weiss, Robert H (2016) Extraction and Quantification of Tryptophan and Kynurenine from Cultured Cells and Media Using a High Performance Liquid Chromatography (HPLC) System Equipped with an Ultra-Sensitive Diode Array Detector. Bio Protoc 6:
Pan, Amy; Zhang, Hongyong; Li, Yuanpei et al. (2016) Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer. Nanotechnology 27:425103
Wang, Sisi; Zhang, Hongyong; Scharadin, Tiffany M et al. (2016) Molecular Dissection of Induced Platinum Resistance through Functional and Gene Expression Analysis in a Cell Culture Model of Bladder Cancer. PLoS One 11:e0146256
McCartt, A D; Ognibene, T; Bench, G et al. (2015) Measurements of Carbon-14 With Cavity Ring-Down Spectroscopy. Nucl Instrum Methods Phys Res B 361:277-280

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