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Developmental genetics in Dictyostelium
- Functional genomics
We have used microarrays to discover gene function in development (Booth et al., 2005), de-differentiation (Katoh et al., 2004), spore germination (Xu et al., 2004),
and in drug resistance (Van Driessche et al., 2007). We also showed that the microarray is a good phenotyping tool for discovering epistatic relationships between six genes in the
cAMP-dependent Protein Kinase regulatory pathway (Van Driessche et al., 2005). In collaboration with Dr. Kuspa, we are generating insertional mutations in most Dictyostelium genes and
using the mutants to discover gene function by parallel phenotyping and by expression analysis.
- The evolution of social behavior in Dictyostelium
Social organisms must deal with cheaters – individuals that reap the benefits of sociality without paying the costs. In Dictyostelium, some cells sacrifice themselves to benefit
other cells that may be genetically different, providing a fertile ground for cheating. In collaboration with Drs. Strassmann and Queller at Rice University and Dr. Kuspa at BCM we found over 100
genes that participate in social interactions (Santorelli et al., 2008). We are using genetics to find and characterize additional genes that determine social decisions, find whether they
are involved in rapid-evolutionary arms races, and test how cooperators resist cheating (Foster et al., 2004; Khare and Shaulsky, 2006).
- Data mining
We are collaborating with Dr. Blaz Zupan and his group at the University of Ljubljana in Slovenia to develop new concepts in genetic analysis. Together we have developed a tool that performs
automated epistasis analysis (http://genepath.org/). We also developed a tool that analyzes regulatory sequences in eukaryotic promoters
(http://dictybase.org/). We are currently developing a web tool that would access and analyze all of our microarray data.
- bZIPs and the regulation of gene expression
A central signaling molecule in Dictyostelium is the Differentiation Inducing Factor (DIF-1) – a chlorinated alkylphenone. The mechanism of DIF signal reception is unknown. We isolated
several strains that are insensitive to DIF-1 and identified dimA, which encodes a bZIP transcription factor (Thompson et al., 2004). We found another bZIP, dimB, that has
overlapping functions with dimA (Huang et al., 2006). We are now mutating the remaining 17 bZIPs in the Dictyostelium genome to investigate their functions.
Selected Publications
Foster KR, Shaulsky G, Strassmann JE, Queller DC, Thompson CR (2004) Pleiotropy as a mechanism to stabilize cooperation. Nature 431:693-696.
Eichinger L, et al., Shaulsky G, et al. (2005) The genome of the social amoeba Dictyostelium discoideum. Nature 435:43-57.
Van Driessche N, Demsar J, Booth EO, Hill P, Juvan P, Zupan B, Kuspa A, Shaulsky G (2005) Epistasis analysis with global transcriptional phenotypes. Nature Genetics
37:471-477.
Juvan P, Demsar J, Shaulsky G, Zupan B (2005) GenePath: from mutations to genetic networks and back. Nucleic Acids Research 33:W749-752.
Booth EO, Van Driessche N, Zhuchenko O, Kuspa A, Shaulsky G (2005) Microarray phenotyping in Dictyostelium reveals a regulon of chemotaxis genes. Bioinformatics
21:4371-4377.
Huang E, Blagg SL, Keller T, Katoh M, Shaulsky G, Thompson CR (2006) bZIP transcription factor interactions regulate DIF responses in Dictyostelium. Development
133:449-458.
Khare A, Shaulsky G (2006) First among equals: competition between genetically identical cells. Nature Reviews Genetics 7:577-583.
Van Driessche N, Alexander H, Min J, Kuspa A, Alexander S, Shaulsky G (2007) Global transcriptional responses to cisplatin in Dictyostelium discoideum identify potential drug
targets. Proceedings of the National Academy of Sciences U.S.A. 104:15406-15411.
Santorelli LA, Thompson CR, Villegas E, Svetz J, Dinh C, Parikh A, Sucgang R, Kuspa A, Strassmann JE, Queller DC, Shaulsky G (2008) Facultative cheater mutants reveal the genetic
complexity of cooperation in social amoebae. Nature 451:1107-1110.
Contact Information
- Gad Shaulsky, Ph.D.
- Department of Molecular and Human Genetics
- Baylor College of Medicine
- One Baylor Plaza S430
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-8082
- Fax: (713) 798-5386
- E-mail: gadi@bcm.tmc.edu
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