Professor, Baylor College of Medicine
Vice President for Research, Baylor College of Medicine
Salih J. Wakil Endowed Chair
B.A., University of California, San Diego, 1982
Ph.D., Stanford University, CA, 1989
Postdoc, University of California, San Diego, 1989-93
Signal transduction, cell differentiation, and genomics of Dictyostelium discoideum
One long-term goal of our laboratory is to define the cellular regulatory mechanisms that govern cell differentiation in eukaryotes using Dictyostelium discoideum as a model. Dictyostelium cells normally live as solitary amoebae in the soil, consuming other microbes by phagocytosis. Upon starvation, ~50,000 cells aggregate into a mound and become an integrated multicellular organism with distinct tissue types. Each organism consists of about 70% prespore cells and 30% prestalk cells. When conditions are favorable, they form a fruiting body, the terminal developmental structure that is made up of a sorus of dormant spores held aloft on a cellular stalk. This system can be used to provide a complete picture of the regulation of a significant biological problem: the integration of individual cells into a multicellular tissue with the proper form and function. Previously, we had studied two ABC transporters, RhT and TagA, that operate very early in development and which control aspects of initial cell differentiation. We have also characterized several components of the regulatory network that governs the growth to development transition itself: a novel putative receptor/kinase GdtB, a conserved protein kinase YakA and a conserved translational regulator PufA. These five regulators form critical links in the regulatory network that controls growth, the decision to initiate development and initial establishment of specific cell types- regulation that is common to all eukaryotes that undergo development. The function of these signaling pathways in Dictyostelium are being studied by genetic, physiological and genomic methods.
Functional genomics holds the promise that we can define most of the significant functions of cells and organisms by using genome-scale techniques to obtain a global view of biological systems. Genomics approaches will provide a unique perspective of biological regulation by completing the “parts lists” for cellular functions and by outlining connections between regulatory systems that could not be obtained by other methods. Before we can fully exploit this information we must identify the genes, understand how the genes function and integrate this information into a comprehensive biological picture. We are involved in the international effort to sequence the 34 Mb genome of Dictyostelium together with the Genome Sequencing Center here. We are also planning to generate mutations in about 5,000 genes and phenotype the resulting strains using a variety of traditional and genomic methods. This work will allow us to make testable predictions of gene function and to propose regulatory networks. We are interested in those aspects of Dictyostelium biology that are common to all eukaryotic organisms, and that will be informative for defining both the function of individual genes and the organization of regulatory hierarchies that operate in development. The relative simplicity and genetic tractability of organisms such as Dictyostelium should prove to be advantageous for genomic analyses of multicellular development.
Good JR, Cabral M, Sharma S, Yang J, Van Driessche N, Shaw CA, Shaulsky G, Kuspa A (2003) TagA, a putative serine protease/ABC transporter of Dictyostelium that is required for cell fate determination at the onset of development. Development 130:2953-2965.
Chen G, Shaulsky G, Kuspa A (2004) Tissue-specific G1-phase cell-cycle arrest prior to terminal differentiation in Dictyostelium. Development 131:2619-2630.
Chen G, Kuspa A (2005) Prespore cell fate bias in G1 phase of the cell cycle in Dictyostelium discoideum. Eukaryotic Cell 4:1755-1764.
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.
Cabral M, Anjard C, Loomis WF, Kuspa A (2006) Genetic evidence that the acyl coenzyme A binding protein AcbA and the serine protease/ABC transporter TagA function together in Dictyostelium discoideum cell differentiation. Eukaryotic Cell 5:2024-2032.
Chen G, Zhuchenko O, Kuspa A (2007) Immune-like phagocyte activity in the social amoeba. Science 317:678-681.
Katoh M, Chen G, Roberge E, Shaulsky G, Kuspa A (2007) Developmental commitment in Dictyostelium discoideum. Eukaryotic Cell 6:2038-2045.
Hirose S, Benabentos R, Ho HI, Kuspa A, Shaulsky G (2011) Self-recognition in social amoebae is mediated by allelic pairs of tiger genes. Science 333:467-470.
Khare A, Santorelli LA, Strassmann JE, Queller DC, Kuspa A, Shaulsky G (2009) Cheater-resistance is not futile. Nature 461:980-982.
Cabral M, Anjard C, Malhotra V, Loomis WF, Kuspa A (2010) Unconventional secretion of AcbA in Dictyostelium discoideum through a vesicular intermediate. Eukaryotic Cell 9:1009-1017.
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.
Adam Kuspa, Ph.D.
Department of Biochemistry and Molecular Biology
Baylor College of Medicine
One Baylor Plaza T321
Houston, Texas 77030, U.S.A.
Tel: (713) 798-8278
Fax: (713) 798-9438