This Program Project is aimed at understanding the mechanisms that control growth and multicellular development in Dictyostelium. By examining the functions of a large number of genes we will begin to formulate a global view of the regulatory networks In this organism. In the previous project period we took a functional genomics approach to high-throughput mutant phenotyping, using molecular barcodes, that has allowed us to draw functional inferences for hundreds of genes. We will revolutionize our parallel phenotyping platform using Next Generation Sequencing technologies that should yield dramatic improvements in barcode quantification so that more information can be gleaned from every new experiment. Over the next five years we will focus our efforts on understanding bacterial recognition in Dictyostelium, both during the growth of solitary amoebae and in the context of an innate immune response during development. We will define innate immune recognition of bacteria by amoebae in molecular terms by characterizing the genes and pathways involved. We will intersect the transcriptional profiling data from Project II with the physiological data provided by this project to uncover links between gene function and patterns of gene expression. The data we produce will also be used by Project 111 for extracting information about the genetic networks that coordinate bacterial recognition in Dictyostelium

Public Health Relevance

This work will help establish the amoeba as a model system for the study of innate immunity, leading to the development of tools and techniques that can be applied to understanding the response of eukaryotic cells to bacteria. Studying the response of amoebae to bacteria has a relation to infections in humans because the work will reveal conserved pathways used by eukaryotes to defend themselves against bacteria.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
2P01HD039691-11
Application #
8252937
Study Section
Special Emphasis Panel (ZHD1-DSR-N (50))
Project Start
2011-10-01
Project End
2017-04-30
Budget Start
2012-05-15
Budget End
2013-04-30
Support Year
11
Fiscal Year
2012
Total Cost
$377,469
Indirect Cost
$136,275
Name
Baylor College of Medicine
Department
Type
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Cai, Huaqing; Katoh-Kurasawa, Mariko; Muramoto, Tetsuya et al. (2014) Nucleocytoplasmic shuttling of a GATA transcription factor functions as a development timer. Science 343:1249531
Zitnik, Marinka; Zupan, Bla┼ż (2014) Gene network inference by probabilistic scoring of relationships from a factorized model of interactions. Bioinformatics 30:i246-i254
Zitnik, Marinka; Zupan, Blaz (2014) Matrix factorization-based data fusion for gene function prediction in baker's yeast and slime mold. Pac Symp Biocomput :400-11
Weirauch, Matthew T; Yang, Ally; Albu, Mihai et al. (2014) Determination and inference of eukaryotic transcription factor sequence specificity. Cell 158:1431-43
Miranda, Edward Roshan; Rot, Gregor; Toplak, Marko et al. (2013) Transcriptional profiling of Dictyostelium with RNA sequencing. Methods Mol Biol 983:139-71
Miranda, Edward Roshan; Zhuchenko, Olga; Toplak, Marko et al. (2013) ABC transporters in Dictyostelium discoideum development. PLoS One 8:e70040
Nasser, Waleed; Santhanam, Balaji; Miranda, Edward Roshan et al. (2013) Bacterial discrimination by dictyostelid amoebae reveals the complexity of ancient interspecies interactions. Curr Biol 23:862-72
Huang, Eryong; Talukder, Shaheynoor; Hughes, Timothy R et al. (2011) BzpF is a CREB-like transcription factor that regulates spore maturation and stability in Dictyostelium. Dev Biol 358:137-46
Sucgang, Richard; Kuo, Alan; Tian, Xiangjun et al. (2011) Comparative genomics of the social amoebae Dictyostelium discoideum and Dictyostelium purpureum. Genome Biol 12:R20
Loomis, William F; Shaulsky, Gad (2011) Developmental changes in transcriptional profiles. Dev Growth Differ 53:567-75

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