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 III for extracting information about the genetic networks that coordinate bacterial recognition in Dictyostelium.
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.
|Li, Cheng-Lin Frank; Santhanam, Balaji; Webb, Amanda Nicole et al. (2016) Gene discovery by chemical mutagenesis and whole-genome sequencing in Dictyostelium. Genome Res 26:1268-76|
|Katoh-Kurasawa, Mariko; Santhanam, Balaji; Shaulsky, Gad (2016) The GATA transcription factor gene gtaG is required for terminal differentiation in Dictyostelium. J Cell Sci :|
|Zhang, Xuezhi; Zhuchenko, Olga; Kuspa, Adam et al. (2016) Social amoebae trap and kill bacteria by casting DNA nets. Nat Commun 7:10938|
|Chen, Xinlu; KÃ¶llner, Tobias G; Jia, Qidong et al. (2016) Terpene synthase genes in eukaryotes beyond plants and fungi: Occurrence in social amoebae. Proc Natl Acad Sci U S A 113:12132-12137|
|Zitnik, Marinka; Zupan, Blaz (2016) COLLECTIVE PAIRWISE CLASSIFICATION FOR MULTI-WAY ANALYSIS OF DISEASE AND DRUG DATA. Pac Symp Biocomput 21:81-92|
|Å½itnik, Marinka; Zupan, BlaÅ¾ (2015) Gene network inference by fusing data from diverse distributions. Bioinformatics 31:i230-9|
|Santhanam, Balaji; Cai, Huaqing; Devreotes, Peter N et al. (2015) The GATA transcription factor GtaC regulates early developmental gene expression dynamics in Dictyostelium. Nat Commun 6:7551|
|Brdar, Sanja; CrnojeviÄ‡, Vladimir; Zupan, Blaz (2015) Integrative clustering by nonnegative matrix factorization can reveal coherent functional groups from gene profile data. IEEE J Biomed Health Inform 19:698-708|
|Hirose, Shigenori; Santhanam, Balaji; Katoh-Kurosawa, Mariko et al. (2015) Allorecognition, via TgrB1 and TgrC1, mediates the transition from unicellularity to multicellularity in the social amoeba Dictyostelium discoideum. Development 142:3561-70|
|Rosengarten, Rafael D; Beltran, Pamela R; Shaulsky, Gad (2015) A deep coverage Dictyostelium discoideum genomic DNA library replicates stably in Escherichia coli. Genomics 106:249-55|
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