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Integrative Neuroscience Initiative on Alcoholism

关于酗酒的综合神经科学倡议

基本信息

批准号：
9242459
负责人：
Robert A Harris
金额：
$ 48.1万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-01 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9242459
关键词：
Address Alcohol consumption Alcohol dependence Alcoholism Animals Basic Science Behavioral Behavioral Assay Biological Biological Assay Brain Brain imaging Candidate Disease Gene Clinical Collaborations Communication Data Data Set Databases Development Drug Targeting Electrophysiology (science)Ensure Evaluation FDA approved Gene Expression Gene Targeting Genes Genetic Genomics Goals Heavy Drinking Human Immune Immune signaling Interdisciplinary Study Laboratories Laboratory Study Leadership Link Measures Modeling Mutation National Institute on Alcohol Abuse and Alcoholism Neurobiology Neuroimmune Neurosciences Pathway interactions Pharmaceutical Preparations Pharmacology Pharmacotherapy Phase Privatization Progress Reports Publications RNA Splicing Reproducibility Research Research Design Research Personnel Research Project Grants Resource Sharing Resources Rodent Rodent Model Role Scientist Stress Structure System Testing Texas Time Translating Translations Untranslated RNA Update Validation Variant alcohol abuse therapy alcohol research alcohol use disorder base behavior test computerized tools computing resources conflict resolution data access data management data sharing design drinking drug candidate drug testing genome wide association study meetings multidisciplinary neural circuit neuroadaptation neuroinflammation new technology nonhuman primate novel research study response sex small molecule symposium transcriptome sequencing treatment strategy web site

项目摘要

PROJECT SUMMARY This is a competing renewal application for the Integrative Neuroscience Initiative on Alcoholism (INIA)- Neuroimmune consortium (Notice# RFA-AA-16-004/005/006) to identify drug targets based on the genomic, cellular, and behavioral neuroadaptations related to excessive alcohol consumption. INIA-Neuroimmune (INIA- N) will address several NIAAA goals, including: 1) understanding the genomics, electrophysiology, and pharmacology of brain immune pathways and their role in alcohol use disorders (AUDs); 2) using new technologies to study neural circuits involved in excessive alcohol drinking; 3) promoting data reproducibility and translation through testing in multiple species (including humans), multiple laboratories, and multiple assays; 4) using emerging computational resources that connect gene networks to drugs to identify compounds with potential to reduce excessive drinking. A key goal for INIA-N is to probe cross-species genomic datasets, together with novel computational approaches, to predict FDA-approved drugs that can be repurposed to treat AUDs. The overall hypothesis for INIA-N is that excessive alcohol consumption causes genetic changes and neuroadaptations in immune-related pathways that are conserved across multiple species (including humans), allowing for the systematic selection and testing of drug targets from the computational to the clinical level. Ten Research Components, two Scientific Cores, and an Administrative Core comprise the consortium. INIA-N will be directed by the Administrative Core in cooperation with the Executive and Steering Committees and guided by a distinguished Scientific Advisory Board. The Administrative Core will provide leadership, oversight of scientific projects, authentication of study drugs, and integration and translation of project data. INIA-N has four goals: 1) Expand our rodent and human genomic studies to include non-human primates (in collaboration with INIA-Stress) and new rodent models, and integrate these with existing datasets. We will also integrate genetic (genome-wide association studies) and genomic analyses (new human RNA-Seq datasets) to facilitate drug target identification, with an emphasis on neuroimmune targets and the unexplored role of novel non-coding RNAs and splice variants in alcohol consumption; 2) Combine extensive genomic resources with new computational approaches to identify candidate drugs that may be repurposed to treat AUDs. These drugs will be tested in several animal drinking models; 3) Apply systems-level approaches (electrophysiology and live brain imaging) to understand how excessive drinking changes brain function, with an emphasis on our top neuroimmune targets; 4) Select leading candidates that emerge from rigorous behavioral and functional testing to study in the new human laboratory component. INIA-N research encompasses a unique `gene network to pharmacotherapy' approach to apply cutting-edge computational tools to nominate gene targets and drugs from our extensive genomic databases and systematically test these candidates in functional and behavioral assays.

项目总结