Our overall objective is to develop a strategy to quantitatively measure protein-protein interactions in signaling networks identified in our phosphoproteome analysis of the Phencyclidine (PCP) Pre-Pulse Inhibition (PPI) model in rats. This research paradigm models a specific cognitive phenotype observed in human schizophrenia. Our previous studies observed perturbation to signaling networks and in this grant period we propose to develop methods to quantitatively measure specific protein-protein interactions of 30 proteins to create a network of proteins altered by PCP/PPI. By examining the interactions of rats treated with PCP to those not treated, we will gain an understanding of how the network is perturbed. We will exploit 15N labeling of rats for quantitative global analysis of the protein complexes comprising part of the signal transduction pathways identified during the previous grant period. Signal transduction is a key elicitor of a diverse array of functions in the brain that impacts different behaviors. The development of technology to analyze 15N labeled rat brain proteins to determine quantitative changes in the network involved in PCP treatment will advance our understanding of molecular changes occurring in this surrogate for the schizophrenia phenotype. In this project, we will develop methods for identifying and quantifying the protein complexes and develop a strategy to perform mixed bottom up and top down of the protein complexes to determine the isoforms and modified of the proteins involved in the complexes. Our hypothesis is that this approach will identify specific molecular processes disrupted by disease. The long term goal is to develop methods and technologies to determine the molecular basis of affective disorders, a health issue for roughly 20 million Americans (5-7% of the population).

Public Health Relevance

Approximately, 20 million Americans are stricken with affective disorders of some type. This research will help establish approaches for examining the molecular processes associated with these disorders. A fundamental understanding of these processes will help the development of therapeutics to alleviate the symptoms associated with affective disorders such as schizophrenia, psychosis, bipolar disorder, and depression.

National Institute of Health (NIH)
Research Project (R01)
Project #
Application #
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Nadler, Laurie S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Scripps Research Institute
La Jolla
United States
Zip Code
Brennand, K; Savas, J N; Kim, Y et al. (2015) Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia. Mol Psychiatry 20:361-8
Fonslow, Bryan R; Stein, Benjamin D; Webb, Kristofor J et al. (2014) Addendum: Digestion and depletion of abundant proteins improves proteomic coverage. Nat Methods 11:347-8
Firat-Karalar, Elif Nur; Rauniyar, Navin; Yates 3rd, John R et al. (2014) Proximity interactions among centrosome components identify regulators of centriole duplication. Curr Biol 24:664-70
Fonslow, Bryan R; Moresco, James J; Tu, Patricia G et al. (2014) Mass spectrometry-based shotgun proteomic analysis of C. elegans protein complexes. WormBook :1-18
Shen, Wanhua; Liu, Han-Hsuan; Schiapparelli, Lucio et al. (2014) Acute synthesis of CPEB is required for plasticity of visual avoidance behavior in Xenopus. Cell Rep 6:737-47
Park, Sung Kyu Robin; Aslanian, Aaron; McClatchy, Daniel B et al. (2014) Census 2: isobaric labeling data analysis. Bioinformatics 30:2208-9
Qin, Xiaoyan; Zheng, Chaoya; Yates 3rd, John R et al. (2014) Quantitative phosphoproteomic profiling of PINK1-deficient cells identifies phosphorylation changes in nuclear proteins. Mol Biosyst 10:1719-29
Bamberger, Casimir; Pankow, Sandra; Park, Sung Kyu Robin et al. (2014) Interference-free proteome quantification with MS/MS-based isobaric isotopologue detection. J Proteome Res 13:1494-501
Choi, Min Sik; Nakamura, Tomohiro; Cho, Seung-Je et al. (2014) Transnitrosylation from DJ-1 to PTEN attenuates neuronal cell death in parkinson's disease models. J Neurosci 34:15123-31
Magdeldin, Sameh; Yamamoto, Keiko; Yoshida, Yutaka et al. (2014) Deep proteome mapping of mouse kidney based on OFFGel prefractionation reveals remarkable protein post- translational modifications. J Proteome Res 13:1636-46

Showing the most recent 10 out of 96 publications