This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This core consists of four driving biological projects. They represent the beneficiaries and catalysts of the computational science and computational tools proposed in Cores 1 and 2, respectively. They represent a wide army of neuroscience, including modeling the brains of healthy developing children (DBP 1), mapping the degenerative processes of Alzheimer''s disease and those at risk (DBP 2), charting the progression of multiple sclerosis in humans and animal models (DBP 3) and relating the genetics and morphology of Schizophrenia (DBP 4). These four projects were carefully chosen to provide not only a wide range of applications with which to test and push the developments of Cores 1 and 2 but also because these are critical, exciting scientific problems that cannot be addressed with existing and conventional methodology. Furthermore, the computational science and tools will pull the sophistication of the biological queries by relating previously independent observations into comprehensive, integrative representations. Genotype and phenotype will be related within a computational atlas and changes over time will be modeled multidimensionally. Our DBP''s include translational research. There are both animal and human studies. There is cross sectional and longitudinal data. Some data comes from existing databases other data will be acquired. Three of the four are relatively mature efforts where immediate benefits will be realized once the computational science and tools of Cores 1 and 2 become available. Preliminary data is provided in each DBP with clear evidence for collaborative enthusiasm. The principal investigator of each DBP already has a strong track record of productivity, a deep understanding of the biological science and considerable knowledge of the computational strategies proposed in our CCB. On a more practical note, these are driving biological projects with considerable potential. They will lead to additional investigation and will be continued beyond the 3 years described in this proposal by extending them with additional applications for independent grant support. That in no way suggests that their relationship with the CCB will cease at the end of the 3-year budget period in the CCB. We have a plan and procedure to encourage, support and select additional DBP''s (see Core 7) to maintain the ''pipeline'' of these projects. We have a plan to support junior investigators to help mature fledgling DBP efforts into competitive DBP worthy of support by the CCB and eventually to stand on their own as independently funded yet collaboratively linked efforts. The four DBP''s that follow were written in NIH R01 format and hence each is described individually. It should be noted however, that there is considerable potential for and expectation of cross-fertilization of ideas and approaches in these projects.
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