Professor

E-mail:rhk2@columbia.edu


Our laboratory studies the evolution and development of Dictyostelium discoideum, which is a soil amoeba that is capable of extraordinary multi-cellular development. These amoebae remain solitary as they feed on bacteria in the soil, but when the food is removed, they shut down their cell cycle and initiate a complex series of gene inductions that leads to the aggregation of the amoebae and eventually, to the formation of a fruiting body. The genetic and biochemical advantages of the organism make it attractive for a number of problems in cell and developmental biology.

The main focus of the lab is currently on a pathway called macroautophagy, the non-specific turnover of bulk protein. It is a system well studied in Saccharomyces cerevisiae and is activated by starvation. Additional studies have been done in mammalian cells and the plant, Arabidopsis thaliana. Because Dictyostelium has a more complicated endolysosomal system (or at least more similar to mammalian cells) than yeast and offers a genetically tractable system, we are currently working to knock out Dictyostelium orthologues of the Autophagy genes identified in Saccharomyces. So far, we have been successful in knocking out atg1, atg5, atg6, atg7, and atg8. Mutations in the Autophagy pathway block development, but do not affect growth. Various studies of these mutants have confirmed the molecular details of autophagy elucidated in yeast and add to our knowledge of the role of particular autophagy genes including atg1. Preciously unknown autophagy genes have been recovered using new methods derived for Dictyostelium We hope to understand how the autophagosomes are formed and how they interact with the lysosomal pathway.

Besides the study of Dictyostelium development, we are investigating the utility of this organism as a host or model for the study of microbial pathogens. One strategy to study the interactions between a pathogen and its host is the use of genetically tractable host models to study infections by identifying resistant host mutants. With this in mind, we tested whether Dictyostelium could be used as a host model for the opportunistic pathogen Legionella pneumophila.

In addition to these projects, the laboratory is involved in deriving a system of genetic analysis and maintains a strong interest in the evolution of these organisms.


[nematode]

A C. elegans dauer larva in a D. Discoideum fruiting body. See ref. 3.


Bibliography:

  1. R.H. Kessin, and M.M. Van Lookeren Campagne. The development of a social amoeba. American Scientist 80: 556-565 (1992).
  2. L. Wu, D. Hansen, J. Franke, R.H. Kession, and G.J. Podgorski. Regulation of Dictyostelium early development genes in signal transduction mutants. Dev. Biol. 171:149-158 (1995).
  3. R.H. Kessin, G.G. Gundersen, M. Grimson, and R. L. Blanton. How slime molds evade nematodes. PNAS 93: 4857-4861 (1996).
  4. R.H. Kessin. The evolution of the cellular slime molds: Dictyostelium - A model system for cell and developmental biology. Universal Academy Press (1997).
  5. E. Palsson, K. J. Lee, R.E. Goldstein, J. Franke, R.H. Kessin and E. C.Cox. Selection for spiral waves in the social amoebae Dictyostelium. PNAS 94:13710-13723 (1997).
  6. S. Pukatzki, N. Tordilla, J. Franke, and R.H. Kessin. A novel component involved in ubiquitination is required for development of Dictyostelium discoideum. J. Biol. Chem. 273:24131-24138 (1998).
  7. S. H.L. Ennis, D.N. Dao, S.U. Pukatzki, R.H. Kessin. Dictyostelium amoebaelacking an F-box protein form spores rather than stalk in chimeras withwild type. PNAS 97:3292-3297 (2000). http://www.pnas.org/cgi/content/abstract/050005097
  8. D.N. Dao, R.H. Kessin, H.L. Ennis. Developmental cheating and the evolutionary biology of Dictyostelium and Myxococcus. Microbiology 146 ( Pt 7):1505-12 (2000).
  9. Pukatzki S, Ennis HL, Kessin RH. A genetic interaction between a ubiquitin-like protein and ubiquitin-mediated proteolysis in Dictyostelium discoideum(1). Biochim Biophys Acta. 1499(1-2):154-163. (2000).
  10. Otto GP, Wu MY, Kazgan N, Anderson OR, Kessin RH. Macroautophagy is required for multicellular development of the social amoeba Dictyostelium discoideum. J Biol Chem. 278(20):17636-45. (2003). For full article
  11. Tekinay T, Ennis HL, Wu MY, Nelson M, Kessin RH, Ratner DI. Genetic Interactions of the E3 Ubiquitin Ligase Component FbxA with Cyclic AMP Metabolism and a Histidine Kinase Signaling Pathway during Dictyostelium discoideum Development. Eukaryot Cell. 2(3):618-26. (2003).
  12. Ennis HL, Dao DN, Wu MY, Kessin RH. Mutation of the Dictyostelium fbxA gene affects cell-fate decisions and spatial patterning. Protist, 154, in press (2003).
  13. Otto GP, Wu MY, Clarke M, Lu H, Anderson OR, Hilbi H, Shuman HA, Kessin RH. Macroautophagy is dispensable for intracellular replication of Legionella pneumophila in Dictyostelium discoideum. Mol Microbiol. 51(1):63-72. (2004). For full article
  14. Otto GP, Wu MY, Kazgan N, Anderson OR, Kessin RH. Dictyostelium macroautophagy mutants vary in the severity of their developmental defects. J Biol Chem. 279(15):15621-9. (2004). For full article
Richard Kessin's Medline citations

Books:


Dictyostelium: The Evolution, Cell Biology, and Development of a Social Organism

Author: Richard H. Kessin, Columbia University

Bibliography by Jakob Franke, Columbia University

Cambridge University Press, 2001.
Available at Amazon.com




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Last modified on May 25, 2004