A major goal for post-genomic biology will be to understand how the one dimensional (1D) genome gives rise to the staggering 3D complexity of the mammalian brain. To address this problem, it will be necessary to spatially map transcripts, proteins, and the networks they form in the brain at a genome-wide level. In this Bioengineering Research Partnership, 3 groups with complementary expertise and an established history of collaboration will combine forces to achieve this goal. (1) At UCLA, Desmond Smith will map gene expression patterns at a genome-wide scale in the mouse brain at volumetric resolutions of 11 ul and 1 ul. This project will employ microarray technology in combination with voxelation, a method for rapid acquisition of expression patterns in the brain. (2) At PNNL, Dick Smith will use voxelation to map protein expression patterns at high throughput using mass spectrometry (FT-ICR MS), again at resolutions of 11 ul and 1 ul. (3) At USC, Richard Leahy will perform image analysis of the data produced by the first 2 aims to create 3D transcript and protein atlases and to extract meaning from the large multivariate data sets that will result. Thus, the first 2 aims will display the relationship between the transcriptome and the proteome in the 3D space of mammalian brain, while the third aim will display the relationships between the brain transcriptome and proteome in the conceptual ID space of the genome.
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