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Core 1: Functional Genomics and Proteomics

核心1：功能基因组学和蛋白质组学

基本信息

批准号：
10704617
负责人：
Nevan J Krogan
金额：
$ 33.22万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-14 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10704617
关键词：
Affinity Affinity Chromatography Atlas of Cancer Mortality in the United States Bioinformatics Biological Assay Biological Sciences Breast CRISPR/Cas technology Cancer Model Cancer cell line Cell Line Cell model Cells Clustered Regularly Interspaced Short Palindromic Repeats Collaborations Complex Computational Biology Core Facility Coupled Cryoelectron Microscopy Data Dependence Disease Education Generations Genes Genetic Genetic Screening Genomic medicine Genomics Goals Head and Neck Squamous Cell Carcinoma Head and neck structure Infrastructure Knock-in Knock-out Lead Mali Malignant Neoplasms Malignant neoplasm of lung Maps Mass Spectrum Analysis Measures Mentors Modeling Molecular Mutate Mutation Outcome PIK3CG gene Pathogenesis Pathology Pathway Analysis Pathway interactions Phenotype Physiological Point Mutation Protein Binding Domain Protein Complex Subunit Protein-Protein Interaction Map Proteins Proteomics Recurrence Reproducibility Research Personnel Research Project Grants Research Support Specificity Squamous Cell Lung Carcinoma Structure Systems Biology TP53 gene Technical Expertise Technology Tertiary Protein Structure Training Variant cancer cell cancer type cell type combinatorial comparative crosslink experimental study fitness functional genomics gain of function insight interest loss of function migration mutant network models novel outreach patient stratification protein complex protein expression protein function protein protein interaction protein purification protein structure reverse genetics software infrastructure stoichiometry targeted cancer therapy targeted treatment tumor progression tumorigenesis

项目摘要

CCMI v2.0 Core 1: Functional Genomics and Proteomics Core Core Lead: Nevan Krogan; Co-Investigator: Prashant Mali SUMMARY Systematic characterization of protein-protein interactions (PPIs) and genetic interaction networks of cancer drivers is critical for the identification of functional complexes for patient stratification and targeted cancer therapies. Proteomic approaches that determine PPIs and protein complex stoichiometry and topology can provide strategic insight into the dynamic cancer landscape and help guide tailored genetic screens to assess functional relevance of newly characterized PPIs. The Functional Genomics and Proteomics Core (Core 1) will provide the infrastructure and technical expertise essential to the completion of the overall CCMI objectives. With support of two Core facilities, the Functional Genomics and Proteomics Core will provide its expertise in CRISPR genetic screens (Institute for Genomic Medicine (IGM) Genomics Center, UCSD) and proteomic technologies (Thermo Fisher Scientific Proteomics Facility for Disease Target Discovery, UCSF, Quantitative Biosciences Institute (QBI), Gladstone Institute) for the generation of high-quality protein-protein (Aim 2; in support of Project 1) and genetic (Aim 1; in support of Project 2) interaction data, which will be integrated using systems biology approaches in Project 3 and Core 2. Our goal is to provide functional and structural characterization of cancer driver networks, model their functional interactions in three different cancers (breast, head and neck, lung cancer), and determine consequences of introducing point mutations. Finally, we will use a unique platform for Endogenous Network/Dynamic Structure (EN/DS) determination (Aim 3) that will use CRISPR-based genetics to introduce point mutations and FLAG-affinity tags into the endogenous loci of selected genes to study endogenous protein complex stoichiometry and structure using mass spectrometry and cryo-EM (in support of Project 1).

CCMI v2.0