William F. Loomis

Distinguished Professor
Section of Cell and Developmental Biology, UCSD

e-mail: wloomis@ucsd.edu
Lab Homepage: Loomis Lab

Temporal and spatial patterns of gene expression underlie development in all organisms but are more easily analyzed in those systems where high resolution genetic techniques can be applied. We focus on cell differentiation in Dictyostelium discoideum where a complete physical map is available and we expect to have the complete sequence of the 34 Mb genome in the next few years (Loomis and Kuspa, 1997; Loomis, 1998). Aggregates of 10⁵ cells are formed within the first 12 hours following the initiation of development and fruiting bodies complete with spores and a cellular stalk are formed in the next 12 hours. This relatively simple developmental sequence can be subdivided into over 10 stages by cell-type specific molecular markers. Using random plasmid insertion mutagenesis (REMI) we have discovered over 150 developmental genes many of which function during development of flies, worms, and mammals while others are novel. The genetic networks that regulate expression of these genes can be recognized by generating complex genotypes using homologous recombination. A combination of biochemical and genetic techniques are used to understand the mechanisms responsible for orderly progression through the stages as well as proper proportioning of the cell types. Saturation screens for suppressor mutations can uncover surprising connections between genes in different parts of the networks (Shaulsky et al., 1998). 

     We are analyzing a two component system that is essential for signal transduction in both prestalk and prespore cells (see Figure). A peptide signal, SDF-2, is released from prestalk cells in a processes dependent on the tagB and tagC genes that are expressed exclusively in prestalk cells. These genes encode serine proteases coupled to ATP driven transporters of the MDR family.  SDF-2 activates a histidine kinase, DhkA, in prespore cells that inhibits the cAMP specific phosphodiesterase, RegA. cAMP can accumulate when the phosphodiesterase is inhibited and activate the cAMP dependent protein kinase PKA. When PKA is activated, prespore vesicles rapidly fuse with the plasma membrane releasing the spore coat proteins that had previously accumulated (Loomis, 1998). The two component system of DhkA and RegA also functions in prestalk cells to gate terminal differentiation. We feel that a conceptual framework is beginning to emerge in which signal transduction pathways can be shown to be connected by intercellular signals. 

Anjard, C. and Loomis, W.F. (2006) GABA induces terminal differentiation of Dictyostelium through a GABAB type receptor. Development 113:2253-2261.

Song, L., Nadkarni, S., Bodeker, H., Beta, C., Bae, A., Frank, C., Rappel, W-J., Loomis, W. F. and Bodenschatz, E. (2006) Dictyostelium discoideum chemotaxis: threshold for directed motion. Eur. J. Cell Biol. 85:981-989.

Cabral, M., Anjard, C., Loomis, W.F., and Kuspa, A. (2006) Genetic evidence that the acyl-CoA binding protein AcbA and the serine protease/ABC transporter TagA function together in  Dictyostelium discoideum cell differentiation. Eukaryotic Cell 5:2024-2032.

Kinseth, M., Anjard, C., Fuller, D., Guizzunti, G., Loomis, W.F. and Malhotra, V. (2007) The Golgi associated protein GRASP is required for unconventional protein secretion during development. Cell 130:524-534.

Anjard, C. and Loomis, W.F. (2008) Cytokinins induce sporulation in Dictyostelium Development  135:819-827.

Loomis, W.F. (2008) cAMP oscillations during aggregation of Dictyostelium. Adv. Exp. Med. Biol.  641:39-48.

    Bill Loomis received his Ph.D. from the Massachusetts Institute of Technology. He received an NIH Senior Research Scientist Fellowship and was named an American Cancer Society Scholar. Professor Loomis is a Fellow of the American Association for the Advancement of Science.