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Center for Systems Neurogenetics of Addiction

成瘾系统神经遗传学中心

基本信息

批准号：
9151757
负责人：
Elissa J Chesler
金额：
$ 258.71万
依托单位：
JACKSON LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-15 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9151757
关键词：
Accounting Acute Adolescent Adopted Affect Awareness Behavior Behavioral Behavioral Genetics Bioinformatics Biological Biological Factors Chromosome Mapping Circadian Dysregulation Circadian Rhythms Cocaine Cocaine Dependence Collaborations Communities Complex Computing Methodologies Core Facility Data Data Analyses Data Set Dependence Deposition Development Diagnostic Disease Drug Addiction Drug Exposure Drug abuse Drug usage Early Intervention Early treatment Education Environment Exhibits Family Fostering Funding Future Gene Expression Profiling Gene Targeting Genes Genetic Genetic Crosses Genetic Variation Genetic study Genomics Genotype Goals Human Human Genetics Impulsivity In Vitro Individual Individual Differences Informatics Institution Intervention Knowledge Laboratories Laboratory mice Lead Link Maps Methodology Mission Modeling Molecular Genetics Molecular Profiling Mus Mutant Strains Mice Mutation Neurosciences Research Nicotine Pathway interactions Pattern Pharmaceutical Preparations Phenotype Population Population Genetics Population Heterogeneity Predisposition Prevention Preventive measure Public Health Quantitative Trait Loci Research Research Activity Research Personnel Research Support Resource Informatics Resources Rewards Risk Risk Factors Sampling Self Administration Self-Administered Services Source Staging Structure Substance Use Disorder System Techniques Testing The Jackson Laboratory Therapeutic Training Validation Variant Work addiction base behavioral study biobank biobehavior cost experience functional genomics genetic analysis genetic variant genome editing holistic approach illicit drug use in vivo in vivo Model innovative technologies insight model development mouse model neurobehavioral neurobiological mechanism neurogenetics novel novel strategies phenomics prevent programs psychostimulant relating to nervous system response sex stimulant abuse symposium tool trait

项目摘要

PROJECT SUMMARY OVERALL COMPONENT The Center for Systems Neurogenetics of Addiction (CSNA) synergizes the expertise and effort of behavioral neuroscientists, computational biologists and geneticists, who each bring state-of-the-art approaches to an integrated research program that will identify and model the common underlying biological mechanisms of biobehavioral risks for stimulant self-administration. Drug addiction is a devastating and highly complex neurobehavioral phenomenon, characterized by multiple etiological factors, stages and behaviors that have proven difficult to study in combination. Advanced mouse genetic populations provide a platform for evaluating the relationships among these behaviors, finding genetic variants responsible for their variation and identifying their associated biological mechanisms and pathways. We will make use of the new Collaborative Cross genetic reference population and Diversity Outbred mapping population to identify the biological mechanisms by which predisposing traits predict the tendency to self-administer the psychostimulant drug cocaine. Each predisposing trait, including impulsivity, acute and sensitized drug responses, reward-seeking, adolescent nicotine exposure and circadian variation, is studied in one of the Center's five scientific projects. Our approach is unprecedented in that we will evaluate these traits simultaneously in a mouse population exhibiting extreme genetic and phenotypic variation, enabling a holistic and extensible assessment of the common and distinct biological mechanisms of addiction vulnerability. We will definitively and directly identify sources of trait correlation in the population. We will produce functional genomics and phenomics datasets, which will be deposited in widely accessed and highly functional informatics resources, where they may be expanded upon by the global research community. Our Center will also generate novel, validated mouse mutants and complex models for mechanistic studies of addiction-related phenomena. In addition to aiding the scientific mission of our five scientific projects, our three research support cores will provide proven, state-of-the-art and innovative technologies to the broader field, including: 1) a sophisticated, large-capacity Behavioral Phenotyping Core, 2) an Integrative Genetics and Genomics Core for statistical genetics, molecular profiling, biobanking and data dissemination, and 3) a Mouse Resource and Validation Core for delivering novel mouse resources for systems genetics, in vitro and in vivo mutation induction and validation. The Administrative Core will oversee the effective coordination, integration and dissemination of the Center's research activities and deliver our findings through The Jackson Laboratory (JAX)'s well-established educational programs. The Pilot Core will offer additional investigators the opportunity to initiate collaborative work with the Center. Through its combined efforts, the CSNA will enable discovery of the mechanisms linking multiple susceptibility phenotypes to the propensity to seek and take drugs, opening up new opportunities for both prevention in those at risk for addiction and intervention in those already afflicted.

项目总结性