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The Psychiatric Cell Map Initiative: Connecting Genomics, Subcellular Networks, and Higher Order Phenotypes

The Psychiatric Cell Map Initiative: Connecting Genomics, Subcellular Networks, and Higher Order Phenotypes
精神病学细胞图谱计划:连接基因组学、亚细胞网络和高阶表型
批准号:
10447106
负责人:
Martin Kampmann
金额:
$370.18万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-05 至 2023-06-30
关键词:
ASCL1 geneAddressArchitectureBiologicalBiological ModelsBiologyBipolar DisorderBrainCRISPR interferenceCRISPR/Cas technologyCaliforniaCatalogingCell modelCellsChemicalsClinicalClustered Regularly Interspaced Short Palindromic RepeatsComplexComputer AnalysisComputer softwareComputing MethodologiesCoupledCryoelectron MicroscopyDNA sequencingDNA-Protein InteractionDataDatabasesDevelopmentDiseaseDockingEngineeringEpilepsyEukaryotic CellFutureGene CombinationsGene ProteinsGenesGeneticGenetic ScreeningGenomicsGenotypeGilles de la Tourette syndromeGoalsHealth ExpendituresHigh-Throughput Nucleotide SequencingHumanIn VitroIndividualIntellectual functioning disabilityKnowledgeLibrariesLigandsLinkMachine LearningMapsMass Spectrum AnalysisMeasuresMental disordersMethodologyMicroscopyModalityModelingMolecularMolecular BiologyMutationNetwork-basedNeurobiologyNeuronsOntologyOrganismPathway interactionsPatientsPhase TransitionPhenotypePoint MutationProductivityProteinsProteomicsResearchResearch PersonnelResolutionResourcesSan FranciscoSchizophreniaScientistSliceStructureSyndromeTadpolesTechnologyTherapeuticTherapeutic InterventionTissuesTrainingTranslatingUniversitiesVariantWorkXenopusautism spectrum disorderautomated image analysisbasebehavioral phenotypingcell typedeep neural networkexcitatory neuronexperimental studygene discoverygene networkin vivoinduced pluripotent stem cellinhibitory neuroninsightinterestlink proteinmolecular phenotypemultidisciplinaryneural networkneuropsychiatric disordernext generationnovelpersonalized medicineprecision medicineprotein complexprotein structurerare variantsingle-cell RNA sequencingsmall moleculesuccesstranscriptome

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SUMMARY The global burden of mental illness, including autism spectrum disorders (ASD), intellectual disability, epilepsy, Tourette disorder, schizophrenia and bipolar disorder, is enormous, whether measured in health care expenditures, lost productivity, or personal suffering. Unfortunately, there is a striking lack of insight into the underlying molecular biology of these syndromes. However, recent advances in gene discovery are setting the stage for a transformation in the understanding of these psychiatric disorders. Understanding pathobiology and developing novel treatments is becoming increasingly dependent on knowledge of biological networks of multiple types, including physical interactions among proteins and synthetic­lethal and epistatic interactions among genes. Here we seek support for a new effort, the Psychiatric Cell Map Initiative (PCMI, www.pcmi.ucsf.edu), aimed at comprehensively understanding these complex interactions in psychiatric disorders and how they differ between diseased and healthy states. While we will focus on ASD in this proposal, this work will establish a paradigm to investigate other psychiatric disorders in future work. The PCMI is a multi­campus initiative of the University of California, involving UC San Francisco, UC San Diego and UC Berkeley, which leverages genomics, proteomics, high­throughput sequencing, advanced network mapping, computational analysis, and research platforms developed by multiple PCMI investigators over the past decade. Thus primed, these platforms will be tuned to efficiently generate, assemble, and analyze molecular networks linked to ASD, in relevant cell types, with a view towards pathway and network­based personalized therapy. Specifically, over the next five years the PCMI will seek to catalyze major phase transitions in ASD research and therapy by (1) Comprehensively mapping the networks of physical interactions among proteins linked to ASD, revealing the protein complexes and higher­order molecular units underlying ASD in multiple cell types of the human brain; (2) Mapping the parallel networks of synthetic­lethal and epistatic interactions among ASD genes using CRISPR­based approaches; (3) Establishing the robust computational methodology, end­user software, and databases for assembly and use of ASD cell network maps in both basic and clinical modalities; (4) Translating molecular insights into an understanding of higher order phenotypes; (5) Building a critical mass of leading investigators focused on psychiatric disorders worldwide to expand PCMI into a global coordinated partnership; and (6) Training the current and next­generation of scientists in Network Biology and its applications to research focused on psychiatric disorders.
期刊论文(6)
专著(0)
科研奖励(0)
会议论文
Modeling Human Genetic Disorders with CRISPR Technologies in Xenopus.
利用 CRISPR 技术在爪蟾中模拟人类遗传疾病。
DOI: 10.1101/pdb.prot106997
发表时间: 2022
期刊: Cold Spring Harbor protocols
影响因子: --
作者: [Willsey HR]
通讯作者: Willsey HR
DOI: 10.1101/pdb.prot105635
发表时间: 2021-10-01
期刊: Cold Spring Harbor protocols
影响因子: --
作者: [Willsey HR]
通讯作者: Willsey HR
DOI: 10.1002/dvg.23405
发表时间: 2021-03
期刊: Genesis (New York, N.Y. : 2000)
影响因子: --
作者: [Exner CRT, Willsey HR]
通讯作者: Willsey HR
DOI: 10.21203/rs.3.rs-3270331/v1
发表时间: 2023-09-18
期刊: Research square
影响因子: --
作者: [Hu M, Alkhairy S, Lee I, Pillich RT, Bachelder R, Ideker T, Pratt D]
通讯作者: Pratt D
Systematic elucidation of endosomal trafficking as a therapeutic opportunity in AD using CRISPR-based functional genomics
Systematic elucidation of endosomal trafficking as a therapeutic opportunity in AD using CRISPR-based functional genomics
Systematic elucidation of endosomal trafficking as a therapeutic opportunity in AD using CRISPR-based functional genomics
Core D: CRISPRi/a Core
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