Biochemistry & Molecular Biology
Functional genomics of the social amoeba Dictyostelium
Drs. Kuspa and Gad Shaulsky received the award for their research on Functional Genomics in the social amoeba Dictyostelium discoideum. Dr. Kuspa initiated the Dictyostelium genome-sequencing project and was responsible for its completion, while Dr. Shaulsky participated in the genome annotation effort and initiated global gene expression analyses. Drs. Kuspa and Shaulsky also pioneered methods for mutating most of the genes in the Dictyostelium genome and developed global gene expression profiles as surrogate phenotypes for gene function discovery. They have also used expression profiling to determine influences between genes by means of genetic epistasis, providing an important proof of principle for the utility of expression profiles as phenotypes. Since Dictyostelium is a close relative of the animals and fungi it provides a system in which gene function can be explored in the context of a simple eukaryote and the results applied to understanding human gene function. The tools and concepts developed by Drs. Kuspa and Shaulsky provide a unique contribution to the effort to identify the function of all the genes in this interesting organism.
Drs. Kuspa and Shaulsky’s nomination was based on the following publications:
Van Driessche N, Shaw C, Katoh M, Morio T, Sucgang R, Ibarra M, Kuwayama H, Saito T, Urushihara H, Maeda M, Takeuchi I, Ochiai H, Eaton W, Tollett J, Halter J, Kuspa A, Tanaka Y, Shaulsky G. A transcriptional profile of multicellular development in Dictyostelium discoideum.
Development. 2002 Apr;129(7):1543-52.
Chen G, Shaulsky G, Kuspa A. Tissue-specific G1-phase cell-cycle arrest prior to terminal differentiation in Dictyostelium. Development. 2004 Jun;131(11):2619-30.
Xu Q, Ibarra M, Mahadeo D, Shaw C, Huang E, Kuspa A, Cotter D, Shaulsky G. Transcriptional transitions during Dictyostelium spore germination. Eukaryot Cell. 2004 Oct;3(5):1101-10.
Eichinger L, et al. The genome of the social amoeba Dictyostelium discoideum. Nature. 2005 May 5;435(7038):43-57.
Drs. Kuspa and Gad Shaulsky have extended their earlier work on the evolution of the soil amoeba Dictyostelium discoideum and related it to the field of social evolution. In times of starvation, the free-living Dicty cells merge into multicellular organisms made up of a non-reproductive stalk and spores. The spores give rise to the next generation, whereas stalk cells die in an altruistic process benefitting the spores. In most cases, the contributions to stalk and spore are in proportion to the populations of dicty cells that form the organisms. However, the existence of "cheater" cells has been known since 2000. "Cheaters" produce spores but do not contribute to the stalk, and it was previously thought that their spread was limited by such factors as developmental defects. However, Shaulsky and Kuspa found over 100 mutations in cheaters demonstrating that the genetic possibility of "cheating" in the system is great and without an evident cost.
Drs. Shaulsky and Kuspa followed up this work with studies on the mechanisms by which natural populations may resist cheaters. They found "cheater-resistant" mutants that can protect other dicty cells from those that cheat. Moreover, these mutants were noble, not using their resistance to exploit other strains but even at times protecting others from the cheater. In a third finding, Drs. Shaulsky and Kuspa found that dicty have a form of immune system that can help them discriminate "self" from "nonself", segregating different strains of the organisms as kin and non-kin. This finding suggests that self-recognition may have evolved as a response to social cheaters.
Drs. Shaulsky and Kuspa's nomination was based on the following publications:
Santorelli, L.A., Thompson, C.R., Villegas, E., Svetz, J., Dinh, C., Parikh, A., Sucgang, R., Kuspa, A., Strassmann, J.E., Queller, D.C., Shaulsky, G. (2008) "Facultative cheater mutants reveal the genetic complexity of cooperation in social amoebae." Nature (451), 1107-1110.
Khare, A., Santorelli, LA., Strassmann, J.E., Queller, D.C., Kuspa, A., & Shaulsky, G. (2009) "Cheater resistance is not futile" Nature, (7266), 980-982.
B Benabentos, R., Hirose, S., Sucgang, R., Curk, T., Katoh, M., Ostrowski, E.A., Strassman, J.E., Queller, D.C., Zupan, B., Shaulsky, G., & Kuspa, A. (2009) "Polymorphic members of the lag gene family mediate kin discrimination in Dictyostelium." Curr Biol, 19(7), 567-572.