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Department of Biochemistry and Molecular Biology

Houston, Texas

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Verna and Marrs McLean Department of Biochemistry and Molecular Biology
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Adam Kuspa, Ph.D.

Dr. Adam Kuspa

Professor
Department of Biochemistry & Molecular Biology
Department of Molecular & Human Genetics
Department of Pharmacology

Vice President for Research

Salih J. Wakil Endowed Chair

Email: akuspa@bcm.edu

Functional Genomics of Dictyostelium

Education and Awards

  • Ph.D., 1989, Biochemistry, Stanford University
  • Postdoctoral, University of California, San Diego
  • American Cancer Society Junior Faculty Research Award, 1995-1999
  • Kinship Foundation, Searle Scholar, 1995-1998
  • BCM, Michael E. DeBakey, M.D., Faculty Excellence in Research Award, 2005

Molecular Genetics of Development in Dictyostelium

Codevelopment of tagB mutant cells
The codevelopment of tagB mutant cells and wild-type Dictyostelium cells reveals the capacity of the mutant to contribute to the various cell types found in migrating slugs (A) and in the final fruiting body (B). The tagB mutant cells contain a prestalk-specific reporter gene so that only prestalk cells produced by tagB cells can be seen (dark pigment). Normally the prestalk cells sort out to the anterior 20% of the slug by 16 hours of development, but the tagB cells are unable to do so when allowed to develop on their own or when mixed with wild-type cells as shown in (A). The cells in the anterior 10% of the slug give rise to the stalk cells, but since the tagB mutant cells do not make these cells, they do not contribute to the final stalk (B).

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 seventy percent prespore cells and thirty percent 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.

Dictyostelium Genomics: 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.

"A Slimy Start to Immunity?" - Kuspa group's research in Science Immunology News.


Publications by Dr. Kuspa

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