Yale/NIDA Neuroproteomics Center

耶鲁大学/NIDA 神经蛋白质组学中心

• 批准号: 10646378
• 负责人: ANGUS C. NAIRN
• 金额: $ 161.61万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646378
• 关键词: Address; Affinity; Alleles; Area; Behavioral; Bioinformatics; Biological Assay; Biological Markers; Biology; Biometry; Biophysics; Biotechnology; Biotinylation; Brain; Brain Chemistry; Brain region; Cannabis; Cells; Central Nervous System; Cocaine; Collaborations; Communication; Country; Data; Development; Drug Addiction; Drug abuse; Environment; Epigenetic Process; Exposure to; Faculty; Fluorescence-Activated Cell Sorting; Fostering; Foundations; Future; Gene Expression; Genomics; Goals; Group Affiliation; Heterogeneity; High Performance Computing; Individual; Institution; Kinetics; Laboratories; Lasers; Ligands; Lipids; Medical Libraries; Mentors; Methodology; Methods; Microscopy; Molecular; Monitor; National Institute of Drug Abuse; Neurobiology; Neurologic; Neurons; Nicotine; Opioid; Organelles; Peptides; Pharmaceutical Preparations; Phosphatidylinositols; Pilot Projects; Play; Post Translational Modification Analysis; Post-Translational Protein Processing; Postdoctoral Fellow; Process; Program Research Project Grants; Property; Proteins; Proteome; Proteomics; Psychiatry; Puromycin; Reaction; Reagent; Records; Regulation; Research; Research Personnel; Research Project Grants; Resources; Rewards; Scientist; Signal Pathway; Signal Transduction; Signaling Protein; Specificity; Structure; Substance abuse problem; Substance of Abuse; System; Techniques; Technology; Thermodynamics; Training; Translations; Work; addiction; biological systems; biophysical analysis; career; cell type; combinatorial; comparative; design; drug action; drug of abuse; histone modification; improved; in vitro Assay; innovation; insight; interest; method development; neural; neuropathology; neuroproteomics; neurotransmission; novel; novel strategies; optogenetics; programs; protein expression; protein profiling; response; synergism; technology development; therapeutically effective; tool; transcriptomics; translatome; virtual

We propose to continuously improve the Yale/NIDA Neuroproteomics Center that brings exceptionally strong Yale programs in proteomics and signal transduction in the brain together with neuroscientists from 8 other institutions across the U.S. to create a national resource that will collaborate to identify adaptive changes in protein signaling that occur in response to substances of abuse. Twenty-three faculty with established records of highly innovative research into the molecular actions of psychoactive addictive drugs, as well as of other basic aspects of neurobiology, will work together in a unique synergy with the Keck Foundation Biotechnology Laboratory to create the Center, whose theme is “Proteomics of Altered Signaling in Addiction”. The Center will use cutting edge proteomic technologies to analyze neuronal signal transduction mechanisms and the adaptive changes in these processes that occur in response to drugs of abuse. With Co-Directors Angus Nairn (Psychiatry) and Kenneth Williams (Mol. Biophys. & Biochem.) in the Administrative Core, the Center includes Discovery Proteomics (DPC) and Targeted Proteomics (TPC) Cores. Biophysical technologies from the DPC will extend protein profiling analyses into the functional domain while lipid analyses from the DPC will leverage proteome level analyses to provide an increasingly biological systems level approach. A Biostatistics and Bioinformatics Core (BBC) that includes high performance computing and the Bioinformatics Support Program in the Yale Medical Library will provide essential support that will leverage the value of each of the proteomic technology cores. A Pilot Research Project Core is a cornerstone in our efforts to encourage strong mentoring relationships that will help attract and train future outstanding scientists. Behavioral adaptations that accompany drug addiction are believed to result from both short and long-term adaptive changes in brain reward centers. Thus, exposure to drugs of abuse regulates intracellular signaling processes that alter gene expression, protein translation, and protein post-translational modifications. Repeated exposure to drugs of abuse leads to stable alterations in these signaling systems that are critical for the changes in brain chemistry and structure of the addicted brain. The Center's research goals include analysis of the actions of cannabis, cocaine, nicotine, and opioids on these intracellular signaling pathways in brain reward areas and development of methods that enable proteomic analysis of the single types of neurons that define the circuits that underlie the actions and addictive properties of drugs of abuse. Targeted and data- independent MS analyses of signaling proteins implicated in the actions of drugs of abuse will be used to analyze the impact of substance abuse on the neuroproteome with motif-based, “Middle-down” MS/MS, and other novel approaches being used to study protein post-translational modifications and to uncover the interactomes of key proteins. A major initiative of the BBC will be to develop novel methods for deep integration of genomic, transcriptomic, and proteomic data with brain region, cell type and allele-specificity.

我们建议继续改进耶鲁大学/NIDA神经蛋白质组学中心，带来卓越的成就

项目成果

Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity.

• DOI: 10.1097/fpc.0b013e328318b21a
• 发表时间: 2009-01
• 期刊: Pharmacogenetics and genomics
• 影响因子: 2.6
• 作者: Hirunsatit R;George ED;Lipska BK;Elwafi HM;Sander L;Yrigollen CM;Gelernter J;Grigorenko EL;Lappalainen J;Mane S;Nairn AC;Kleinman JE;Simen AA
• 通讯作者: Simen AA

Granulocyte-Colony-Stimulating Factor Alters the Proteomic Landscape of the Ventral Tegmental Area.

• DOI: 10.3390/proteomes6040035
• 发表时间: 2018-09-23
• 期刊: Proteomes
• 影响因子: 3.3
• 作者: Mervosh NL;Wilson R;Rauniyar N;Hofford RS;Kutlu MG;Calipari ES;Lam TT;Kiraly DD
• 通讯作者: Kiraly DD

Glutathione and redox signaling in substance abuse.

• DOI: 10.1016/j.biopha.2014.06.001
• 发表时间: 2014-07
• 期刊: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
• 作者: Uys JD;Mulholland PJ;Townsend DM
• 通讯作者: Townsend DM

WNK2 kinase is a novel regulator of essential neuronal cation-chloride cotransporters.

• DOI: 10.1074/jbc.m111.222893
• 发表时间: 2011-08-26
• 期刊: The Journal of biological chemistry
• 作者: Rinehart J;Vázquez N;Kahle KT;Hodson CA;Ring AM;Gulcicek EE;Louvi A;Bobadilla NA;Gamba G;Lifton RP
• 通讯作者: Lifton RP

Nonenzymatic domains of Kalirin7 contribute to spine morphogenesis through interactions with phosphoinositides and Abl.

• DOI: 10.1091/mbc.e13-04-0215
• 发表时间: 2014-05
• 期刊: Molecular biology of the cell
• 影响因子: 3.3
• 作者: Ma XM;Miller MB;Vishwanatha KS;Gross MJ;Wang Y;Abbott T;Lam TT;Mains RE;Eipper BA
• 通讯作者: Eipper BA