Genomics has rapidly developed as a new area of bioscience. Functional genomics evaluates gene expression with the hope of identifying new genes or pathways involved in a developmental system. Hematopoiesis involves a complex differentiation scheme in which changes in gene expression accompany formation of stem cells, selection of lineages, and subsequent differentiation. Recent progress suggests that developmental hematopoiesis should be fertile territory for application of functional genomic strategies. Several NIH initiatives have been launched recently to characterize the mouse and zebrafish genomes. These programs will provide a wealth of new data for investigators. As described here, we are beginning to develop the infrastructure and technical expertise to deal with this new information as it may relative to hematopoiesis. The new CORE proposed here, a CORE for Functional Genomics and Bioinformatics, constitutes a major component of our efforts within the Center. Part of the foundation on which this effort is based is a recent initiative by the NIH in the area of the Zebrafish Genome. Recently, Dr. Zon's laboratory was awarded a new grant, specifically aimed at placing 5,000 genes or EST sequences on the zebrafish genome map. The project includes a supervisor, 3-4 technicians, and a data Hospital. With this genomics lab as a base, we propose to add a functional genomics effort, as detailed below. An informatics component of this CORE will define common and evolutionarily conserved molecular cascades utilized at hematopoiesis. The comparative evaluation of gene expression and function during normal hematopoiesis and several vertebrate systems will add to our understanding of diseases, such as anemias and leukemia, and will have importance for the development of novel, molecularly-based therapies in the future:
Specific Aims : 1. Establish developmental and activated gene expression profiles for the hematopoietic program of several vertebrates and utilize comparative genetics/genomics to find common themes regulating hematopoiesis during vertebrate ontogeny and phylogeny. 2. Provide high density arrays of genomic libraries for experiments involving gene targeting, positional cloning and regulatory element analysis. 3. Establish high throughput genotyping for studies that characterize known mutants or for gene mapping of new mutants.
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