Richard H. Kessin, Ph.D.

Our laboratory studies the evolution and development of Dictyostelium discoideum, which is a soil ameoba 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.

We have taken advantage of insertional mutagenesis techniques to create mutants that are blocked at various stages of development. One of our mutants is blocked at the tight aggregate stage and is defective in a gene called nosA, for no spores. We have recovered this gene, sequenced it and showed that it is involved in proteolysis. In the absence of nosA, patterns of ubiquitination are disturbed. We are currently using suppressor analysis to find genes with which nosA interacts, and biochemical methods to define its role in the proteolytic pathway. Our first results indicate that NosA is involved with the regulation of ubiquitin-like proteins, and not ubiquitin itself. NosA is a poorly defined element of regulated proteolysis and the severe defect that it causes in these cells offers a means to study its role. How regulated proteolysis affects growth and development is one of our major interests.

For a long period we have been interested in the genes that control the chemotactic process that these cells use to aggregate. The cells aggregate toward sources of cAMP. After development starts, the cells synthesize a series of enzymes which are responsible for the synthesis, detection and degradation of cAMP. Almost all of the important genes involved in chemotaxis have been cloned. Our laboratory has been responsible for the cloning and examination of the cAMP phosphodiesterase gene and an unusual gene that codes for a glycoprotein that inhibits the phosphodiesterase. Both of these are essential to normal development. We are now using genetic methods to recover the genes that regulate the early developmental induction of the phoshodiesterase and its inhibitor.

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.

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. Devel. Biol., 171:149-158, (1995).
   
3. R.H. Kessin, G.G. Gundersen, M. Grimson, and R. L. Blanton. How slime molds evade nematodes. Proc. Nat'l. Acad., 93: 4857- 4861, (1996).
   
4. R.H. Kessin. The evolution of the cellular slime molds, Proceedings of the Yamada Foundation Symposium, XLVI edu: Y. Maeda, K. Inouye, I. Takeuchi, (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 Vol. 94, 13710-13723, (1997).
   
6. Stefan Pukatzki, Nelson Tordilla, Jakob Franke, and Richard H. Kessin. A Novel Component Involved in Ubiquitination is Required for Development of Dictyostelium discoideum. Journal of Biological Chemistry, in press (1998).