Our long-term objective is to understand the complex network of genetic interactions that underlies the processes of normal development, disease and evolution. For this, we need to determine gene expression profiles for the full complement of genes in an organism. At the Berkeley Drosophila Genome Project (BDGP), we have established a gene expression resource for Drosophila development that contains spatial and temporal embryonic expression patterns as well as annotations of the patterns using a standardized, controlled vocabulary, based on Gene Ontology (GO). Our database currently contains 75,000 annotated images showing expression patterns generated using in-situ hybridization of staged whole-mounted embryos for approximately 45% (6,000) of the protein-coding genes in the Drosophila genome. The spatial expression data are integrated with our developmental microarray data. We propose to extend these studies to: (1) the remaining 55% of the protein-coding genes, (2) alternatively-spliced transcripts, and (3) non-coding RNA candidate genes The primary resource for generation of RNA probes is our Drosophila Gene Collection (DGC) which currently contains cDNA clones corresponding to 80% of the annotated genes. To capture expression patterns for genes that do not have a representative cDNA clone (20%), we used gene-specific PCR products to generate RNA probes in 96-well format. The gene expression data produced by our study will provide fundamental information for elaborating the function of the 13,664 genes in Drosophila and will aid in elucidating the function of the homologous genes in other eukaryotes, including humans. In addition, the integration of the gene expression data with gene, transcript and protein sequences will promote research to discover networks of regulatory interactions. Using the standardized vocabulary allows cross-species descriptions of gene expression and tissue differentiation. Elucidating the mechanisms responsible for genome-wide gene expression and regulation in Drosophila development will aid in understanding normal growth and differentiation of tissues in humans, prerequisites for understanding human disease. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM076655-02
Application #
7279298
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Haynes, Susan R
Project Start
2006-09-01
Project End
2010-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
2
Fiscal Year
2007
Total Cost
$401,865
Indirect Cost
Name
Lawrence Berkeley National Laboratory
Department
Genetics
Type
Organized Research Units
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
Kudron, Michelle M; Victorsen, Alec; Gevirtzman, Louis et al. (2018) The ModERN Resource: Genome-Wide Binding Profiles for Hundreds of Drosophila and Caenorhabditis elegans Transcription Factors. Genetics 208:937-949
Booth, Benjamin W; McParland, Charles; Beattie, Keith et al. (2018) OpenHiCAMM: High-Content Screening Software for Complex Microscope Imaging Workflows. iScience 2:136-140
Wu, Siqi; Joseph, Antony; Hammonds, Ann S et al. (2016) Stability-driven nonnegative matrix factorization to interpret spatial gene expression and build local gene networks. Proc Natl Acad Sci U S A 113:4290-5
Stoiber, Marcus; Celniker, Susan; Cherbas, Lucy et al. (2016) Diverse Hormone Response Networks in 41 Independent Drosophila Cell Lines. G3 (Bethesda) 6:683-94
Brown, James B; Celniker, Susan E (2015) Lessons from modENCODE. Annu Rev Genomics Hum Genet 16:31-53
Gerstein, Mark B; Rozowsky, Joel; Yan, Koon-Kiu et al. (2014) Comparative analysis of the transcriptome across distant species. Nature 512:445-8
Brown, James B; Boley, Nathan; Eisman, Robert et al. (2014) Diversity and dynamics of the Drosophila transcriptome. Nature 512:393-9
Hammonds, Ann S; Bristow, Christopher A; Fisher, William W et al. (2013) Spatial expression of transcription factors in Drosophila embryonic organ development. Genome Biol 14:R140
Fisher, William W; Li, Jingyi Jessica; Hammonds, Ann S et al. (2012) DNA regions bound at low occupancy by transcription factors do not drive patterned reporter gene expression in Drosophila. Proc Natl Acad Sci U S A 109:21330-5
Thomas, Sean; Li, Xiao-Yong; Sabo, Peter J et al. (2011) Dynamic reprogramming of chromatin accessibility during Drosophila embryo development. Genome Biol 12:R43

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