The NIDA P30 "Center for Molecular and Epigenetic Research of Cell Types Mediating Addictive Behaviors" proposed here will provide to NIH investigators state of the art resources, technologies and expertise that will significantly enhance the programs of each of the participating laboratories, and enable development of additional advanced methodologies that are of general utility for the investigation of mechanisms of drug abuse. To meet these objectives, the Center will be organized into four Cores: The Administrative Core will organize and manage all programmatic and fiscal operations of the Center, including outreach to each of the Center investigators, management of quarterly online meetings of the External Advisory Committee, and hosting of Center investigators or their staff during the conduct of on-site experiments. The BAC Recombineering and Transgenic Targeting Core will generate, characterize and distribute specialized transgenic lines for advanced molecular studies of cell types contributing to addiction circuitry;The Molecular and Epigenetic Profiling Core will provide specialized behavioral and experimental services for the conduct of TRAP translational profiling and epigenetic mapping studies in the context of chronic drug treatment, drug self-administration, and drug withdrawal;The Molecular Informatics Core will provide facilities and expertise to help investigators collect, store and analyze the very large amounts of data that will result from their microarray, TRAPseq, epigenome mapping and ChlPseq studies. The Center will also support a small number of Pilot Projects aimed at developing new technologies that will advance discovery of molecular mechanisms that contribute to drug abuse, or extension of existing approaches to mammalian model systems that have been refractory thus far to modern molecular genetic approaches The outstanding scientists participating in the Center share the belief that: it is beyond the capacity of any participating laboratory to generate the large number of specialized transgenic lines required for comprehensive genetic, molecular and epigenetic analysis of addiction circuits;and that a Center in which their laboratories can apply advanced methods for analysis of addiction circuits will significantly advance their research programs.
Molecular genetic studies of addictive behaviors in animal models have shown that long term adaptations to neural circuits that occur in the context of substance abuse involve alterations gene expression and engage epigenetic mechanisms that mediate cell specific responses to addictive drugs. This center will provide new resources and cutting edge technologies for development of new therapeutic approaches for drug abuse.
|Broms, Jonas; Antolin-Fontes, Beatriz; Tingström, Anders et al. (2015) Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates. J Comp Neurol 523:359-80|
|Fishell, Gord; Heintz, Nathaniel (2013) The neuron identity problem: form meets function. Neuron 80:602-12|