Low-input profiling of brain-region and cell-type specific epigenomic dynamics to understand gene-environment interactions in opioid addiction

对大脑区域和细胞类型特异性表观基因组动力学进行低输入分析，以了解阿片类药物成瘾中的基因与环境的相互作用

• 批准号: 10605801
• 负责人: Julie A Blendy
• 金额: $ 73.23万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605801
• 关键词: 3-Dimensional; Address; Adolescence; Adolescent; Adult; Affect; Animals; Behavior; Behavioral; Bioinformatics; Biological Assay; Biology; Brain; Brain region; Cell Nucleus; Cells; Chromatin Structure; Code; Complex; Cre driver; DNA Sequence; Data; Development; Disease; Drug Addiction; Drug Exposure; Drug Targeting; Drug abuse; Drug usage; Enhancers; Environmental Risk Factor; Epidemic; Epigenetic Process; Exhibits; Exons; Exposure to; Future; Genes; Genetic; Genetic Risk; Genomics; Histones; Human; Incidence; Individual; Knowledge; Life; Life Experience; Link; Literature; Long-Term Effects; Maps; Mediating; Mediation; Morphine; Mus; Mutation; Neuronal Plasticity; Neurons; Opiate Addiction; Opioid; Oxycodone; Pathology; Pharmaceutical Preparations; Phenotype; Physiological Processes; Play; Predisposition; Process; Property; Regulatory Element; Resolution; Rewards; Risk; Risk Factors; Role; Sampling; Self Administration; Single Nucleotide Polymorphism; Specificity; Stimulus; Substance Addiction; Technology; Testing; Therapeutic; Validation; Variant; Work; addiction; bioinformatics tool; cell type; drug development; drug of abuse; drug seeking behavior; enhancing factor; epigenomics; gene environment interaction; genetic variant; genome wide association study; genome-wide; genome-wide analysis; improved; insight; interest; molecular phenotype; mu opioid receptors; opioid exposure; opioid use disorder; promoter; protective allele; response; reward circuitry; risk variant; transcription factor; transcriptome; transcriptome sequencing; transcriptomics

Project Summary Addiction is a physiological process that involves changes in neural plasticity in response to drugs of abuse. Although genetic factors have been recognized as a strong influence on the susceptibility to addition, environmental stimuli and life experiences also form important risk factors. There has been increasing evidence that epigenetic mechanisms mediate the influence of environmental factors on gene activities in the CNS and therefore are likely involved in brain development and pathology of drug abuse. Furthermore, DNA sequence variation is known to impact epigenetic landscape, chromatin structures and molecular phenotypes via influencing the cis-regulatory elements such as promoters and enhancers. In this project, we are interested in probing how epigenomic mechanisms mediate environmental factors such as adolescent drug exposure during addiction development and how a genetic variant affects such mediation. We will use the state-of-the-art omic and bioinformatic technologies to decipher the links among genetics, epigenetics and environmental factors involved in opioid addiction. The low-input approaches will allow us to characterize epigenomic and transcriptomic dynamics with cell-type and brain-region specificity.

项目摘要 成瘾是一个生理过程，涉及神经可塑性的变化，以响应滥用药物。 虽然遗传因素已被认为是一个强大的影响易感性的增加， 环境刺激和生活经历也是重要的风险因素。人们越来越 证据表明，表观遗传机制介导环境因素对基因活动的影响， 因此可能参与大脑发育和药物滥用的病理学。此外，DNA 已知序列变异影响表观遗传景观、染色质结构和分子表型 通过影响顺式调节元件如启动子和增强子。在这个项目中，我们感兴趣的是 在探索表观基因机制如何介导环境因素，如青少年药物暴露， 以及遗传变异如何影响这种调节。我们将使用最先进的 利用组学和生物信息学技术，破译遗传学、表观遗传学和环境之间的联系， 阿片类药物成瘾的因素。低投入的方法将使我们能够表征表观基因组和 具有细胞类型和脑区域特异性的转录组学动力学。