PROJECT SUMMARY/ABSTRACT PILOT PROJECT CORE The Center for Systems Neurogenetics of Addiction (CSNA) will offer pilot project opportunities to support the development of future CSNA-affiliated projects. Pilot projects will create critical opportunities for new investigators to generate key preliminary data for future systems genetic studies of addiction and will enable established investigators to test new hypotheses and migrate their research into the use of novel mouse genetic platforms for the assessment of biobehavioral addiction risk. In the initial phase of the program, we have selected three pilot projects. The first uses the phenomenal genetic diversity in the CC/DO inbred founders to test for modifiers of a new cocaine sensitization quantitative trait gene recently discovered by QTL analysis in closely related mouse strains, Cyfip2, and makes use of the CSNA Behavioral Phenotyping Core to extrapolate the effects of this polymorphism from cocaine sensitization to behavior in drug self-administration paradigms. The second pilot project comes from an established human geneticist. This is a translational genetics project, aimed to model and characterized methamphetamine use-related variants discovered in human genetic studies of addiction. Candidate variants will be engineered into the laboratory mouse using BAC transgenic strategies. These induced variants will be evaluated through a series of behavioral and molecular experiments. A third pilot project will enable integration of the CSNA's transcriptomic and genetic findings with epigenetic analysis by evaluating open chromatin in cocaine treated and control mice from the CC/DO founder strains. Future pilot projects will be selected from an open solicitation to the addiction research community and will be selected by the Internal Advisory Board in consultation with the External Advisory Board through a process coordinated by the Administrative Core. Criteria for the projects include overall impact, innovation, investigator, approach and feasibility within the CSNA, significance and relevance to the center, and likelihood to develop into center-affiliated, funded projects.