Current molecular biological techniques allow us to visualize semi-quantitative levels of gene expression in situ. For example, autoradiographical image data from in situ hybridization histochemistry (ISHH) provides a wealth of information, which if made readily available could be beneficial for neuroscience researchers. However, in most cases due to the scope of their particular research interests this ISHH data has been widely overlooked by many researchers. Thus, much of the gene expression data tends to get discarded or at best becomes unavailable for future review by other researchers. For example, one researcher may have vested interests in the gene expression of brain type nitric oxide synthase (bNOS) in cholinergic nuclei, and other researchers may have interests in the serotonergic nuclei. Until this proposal, there has been no considerable effort to facilitate the sharing of such bNOS gene expression data amongst researchers. In essence, for their particular research interests, these investigators will need to repeat the same bNOS ISHH for their publications, time and time again. In order to eliminate such progress-retarding redundancy, we propose a data sharing system (interactive Multiple Gene Expression Map, IMGEM) that will be available as an interactive brain map of gene expression. This interactive tool will provide benefits essential for continuing to make great strides in discovery and mapping of gene expression by neuroscientists. We will employ the technological advantages of electronic databasing by creating a series of brain atlases as follows: 1) IMGEM will contain 2D images of all brain sections with multiple levels of resolution, 2) by the 2D and 3D image analysis, IMGEM will facilitate the comparison of multiple gene expressions and morphological structures (Niss1-stain), 3) by three dimensional reconstruction of the image data, IMGEM will allow for free rotation of the 3D image and virtual-sectioning of the brain will be possible in any desired plane, 4) IMGEM will include a server-side, graphical interface discussion board (or discussion forum) capability, which will be capable of receiving responses or input from IMGEM users in real-time; and as an additional benefit, IMGEM will be readily edited and updated to reflect the real-time input of online users, 5) IMGEM will be seamlessly integrated with other currently available online databases and hyperlinks to other data resources on the Internet will be highlighted and easily accessible via IMGEM's user-friendly design and navigation. The long-term goal of this current proposal is to gain further insights from the information available (data in the present and future) for brain gene expression mapping; and in so doing, to seek to better apply this collective knowledge for our continued understanding of normal and diseased human brain function. Our laboratory has been providing prominent ISHH data in serial brain sections with special expertise in the combination of ISHH and immunohistochemistry techniques in the same brain section. The applicant has exhibited skilled experience in creation of a commercial software package for multi dimensional data analysis, construction of relational database system on network, computer aided manipulation of imaging data and in programming of HTML, DHTML, VRML, JAVA, CGI and Perl scripts, languages necessary to accomplish the scope of the IMGEM project. Thus, we believe that our laboratory is uniquely, qualified to pursue this current proposal.
