I propose to develop tools, datasets and methods for the genome-wide identification of genes regulated by transcription factors during the embryonic development of Caenorhabditis elegans. During the career development phase, I will use methods we have developed in the Waterston lab to generate an initial map of transcription factor activity with cellular resolution in the C. elegans embryo. In parallel I will develop technology to facilitate the efficient identification of downstream targets of transcription factors in the embryo. Once in my own lab, I will extend these methods to identify and characterize functional targets of many transcription factors on a genomic scale and to explore how transcription factors combine to regulate gene expression. The career development phase will be critical for this effort because of the need for development of methods, and because the transcription factor expression map I propose to produce will provide a critical integrating platform to use when choosing factors for genome-wide analysis and when interpreting the resulting data. Relevance to public health: Knowledge of how transcription factors act in development may provide information about how the same transcription factors function in cancers when inappropriately activated. Furthermore, human orthologs of genes identified in this study as regulated by developmentally important transcription factors may play roles in both normal development and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Career Transition Award (K99)
Project #
5K99GM083145-02
Application #
7534784
Study Section
Special Emphasis Panel (ZGM1-BRT-9 (KR))
Program Officer
Carter, Anthony D
Project Start
2007-12-01
Project End
2009-11-30
Budget Start
2008-12-01
Budget End
2009-11-30
Support Year
2
Fiscal Year
2009
Total Cost
$88,289
Indirect Cost
Name
University of Washington
Department
Biochemistry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Burdick, Joshua; Walton, Travis; Preston, Elicia et al. (2016) Overlapping cell population expression profiling and regulatory inference in C. elegans. BMC Genomics 17:159
Zacharias, Amanda L; Walton, Travis; Preston, Elicia et al. (2015) Quantitative Differences in Nuclear ?-catenin and TCF Pattern Embryonic Cells in C. elegans. PLoS Genet 11:e1005585
Walton, Travis; Preston, Elicia; Nair, Gautham et al. (2015) The Bicoid class homeodomain factors ceh-36/OTX and unc-30/PITX cooperate in C. elegans embryonic progenitor cells to regulate robust development. PLoS Genet 11:e1005003
Churgin, Matthew A; He, Liping; Murray, John I et al. (2014) Construction of a system for single-cell transgene induction in Caenorhabditis elegans using a pulsed infrared laser. Methods 68:431-6
Burdick, Joshua T; Murray, John Isaac (2013) Deconvolution of gene expression from cell populations across the C. elegans lineage. BMC Bioinformatics 14:204
Churgin, Matthew A; He, Liping; Murray, John I et al. (2013) Efficient single-cell transgene induction in Caenorhabditis elegans using a pulsed infrared laser. G3 (Bethesda) 3:1827-32
Abdus-Saboor, Ishmail; Stone, Craig E; Murray, John I et al. (2012) The Nkx5/HMX homeodomain protein MLS-2 is required for proper tube cell shape in the C. elegans excretory system. Dev Biol 366:298-307
Murray, John Isaac; Bao, Zhirong (2012) Automated lineage and expression profiling in live Caenorhabditis elegans embryos. Cold Spring Harb Protoc 2012:
Abdus-Saboor, Ishmail; Mancuso, Vincent P; Murray, John I et al. (2011) Notch and Ras promote sequential steps of excretory tube development in C. elegans. Development 138:3545-55
Bao, Zhirong; Murray, John I (2011) Mounting Caenorhabditis elegans embryos for live imaging of embryogenesis. Cold Spring Harb Protoc 2011:

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