Gad Shaulsky

Developmental genetics in Dictyostelium

• Functional genomics
  
  In the past we have used microarrays to discover gene function in development, de-differentiation, spore germination, drug resistance, and chemotaxis (e.g. Booth et al., 2005; Van Driessche et al., 2007). We also showed that the microarray is a good phenotyping tool for discovering epistatic relationships between genes in the cAMP-dependent Protein Kinase regulatory pathway (Van Driessche et al., 2005). Recently, we started to use RNA-sequencing as our main platform for transcriptional profiling. We compared the developmental transcriptomes of D. discoideum and D. purpureum, two Dictyostelium species whose genomes are as different from each other as the genomes of humans and jawed fish, but whose developmental morphologies are very similar. We found vast similarities between the two transcriptomes (Parikh et al., 2010). The data are available for interactive exploration on dictyExpress. In collaboration with Dr. Adam Kuspa at BCM we are generating thousands of mutant Dictyostelium strains and we are analyzing them using transcriptional profiling. We are currently focusing on ABC transporters and on several transcription factors.
  
  
• 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 and 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 with Dr. Adam Kuspa at BCM, we found over 100 genes that participate in social interactions (Santorelli et al., 2008). We are using genetic tools to characterize mechanisms that determine social interactions and test how cooperators resist cheating (Khare and Shaulsky, 2006; Khare et al., 2009; Khare and Shaulsky, 2010).
  
  
• Allorecognition in Dictyostelium
  
  Multicellular organisms can distinguish self from non-self through various mechanisms. We have found that D. discoideum cells preferentially cooperate with their relatives (Ostrowski et al., 2008), possibly reducing their exposure to strains that can cheat on them. We are now investigating the molecular mechanisms that underlie kin discrimination. We found two cell-cell adhesion genes, tgrB1 and tgrC1, that are highly polymorphic in natural populations and are required for allorecognition (Benabentos et al., 2009). Recent gene replacement experiments have shown that the sequence polymorphism in these genes is sufficient to explain allorecognition in this system. We are investigating the cellular and genetic mechanisms that regulate allorecognition.
  
  
• 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. Previously we have developed a tool that performs automated epistasis analysis, GenePath. We also developed dictyExpress, a web tool that can access and analyze our transcriptional profiling data. We are in the process of developing a tool for automated analysis of RNA-sequencing data.

Selected Publications

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.

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.

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.

Benabentos R, Hirose S, Sucgang R, Curk T, Katoh M, Ostrowski EA, Strassmann JE, Queller DC, Zupan B, Shaulsky G, Kuspa A (2009) Polymorphic members of the lag gene family mediate kin discrimination in Dictyostelium. Current Biology 19:567-572.

Khare A, Santorelli LA, Strassmann JE, Queller DC, Kuspa A, Shaulsky G (2009) Cheater-resistance is not futile. Nature 461:980-982.

Khare A, Shaulsky G (2010) Cheating by exploitation of developmental prestalk patterning in Dictyostelium discoideum. PLoS Genetics 6:e1000854.

Parikh A, Miranda ER, Katoh-Kurasawa M, Fuller D, Rot G, Zagar L, Curk T,Sucgang R, Chen R, Zupan B, Loomis WF, Kuspa A, Shaulsky G (2010) Conserved developmental transcriptomes in evolutionarily divergent species. Genome Biology 11:R35.

Shigenori H, Benabentos R, Ho H-I, Kuspa A, Shaulsky G (2011) Self-recognition in social amoebae is mediated by allelic pairs of tiger genes. Science 333:467-470.

Contact Information

Gad Shaulsky, Ph.D.

Department of Molecular and Human Genetics

Baylor College of Medicine

One Baylor Plaza S930

Houston, Texas 77030, U.S.A.

Tel: (713) 798-8082

Fax: (713) 798-5386

E-mail: gadi@bcm.edu