The main objective of the Chromatin and Gene Analysis Core is to create the technical and bioinformatic infrastructure to generate and mine the vast amounts of genome-wide gene expression and chromatin data that result from the PPG's work. In this way, the Core provides a crucial foundation for research in each of our four Projects, which explore molecular, cellular, and circuit mechanisms that underiie addiction-related behavioral abnormalities. PPG investigators have led the field in several aspects of genome-wide chromatin analyses, including pioneering these approaches in brain, which offers several unique technical challenges. We have defined optimal methods of chromatin immunoprecipitation (ChIP) for rodent and human brain. As well, the Core has established expertise in analyzing the rich ChlP-Seq and RNA-Seq datasets obtained, and will work to continually improve the tools available. Much ofthe new genome-wide data obtained by our PPG will be generated by some ofthe individual Projects and analyzed by the Core. In parallel, the Core is running more routine genome-wide assays and thereby offering a groundwork for the more specific measures in the Projects. Additionally, the Core is piloting several novel technologies and approaches, including methods to target a particular chromatin modification at an individual gene selectively within a given brain region in vivo. The Core is also testing whether any potent trans-generational transmission of behavioral abnormalities might be mediated via epigenetic changes in sperm or ova from drug-exposed mice. By consolidating the analytical work and some routine genome-wide analyses within a centralized Core, we ensure rigorous control over the data and facilitate comparisons of experimental findings across the individual Projects. This consolidation also makes financial sense, since we concentrate and maximize efficient use of the required expertise. Finally, the Core is responsible, with the Administrative Core, for developing and maintaining the multiple ways in which these highly complex and large datasets, and analytical tools, are safely stored and then shared across the multiple Projects and laboratories that comprise the PPG as well as with the scientific community and lay public at large.
Addiction remains one of the worid's greatest public health problems, yet its pathophysiology remains incompletely understood and available treatments for addictions to various drugs of abuse are inadequately effective for most people. We believe that the most effective way of eventually developing definitive treatments and cures for addiction rests in part in a better understanding of its underlying neurobiology.
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