The primary interest of our lab is to understand how developmental genes are regulated during the multicellular developmental program of the bacterium Myxococcus xanthus, and the role of interactions between cells in regulating and coordinating this process. Compared to other prokaryotic organisms, this bacterium has quite an unusual life cycle. When abundant nutrient is present, it grows by normal binary fission. However, when nutrient becomes limiting, a program of multicellular development is initiated. Cells begin by migrating to aggregation foci, in which they form fruiting bodies, compact spherical structures about 0.1 mm in diameter, each containing a few hundred thousand bacterial cells. Within the fruiting body, a portion of the cells differentiate into dormant, environmentally resistant spores; the fate of the remaining cells is uncertain. When nutrient is replenished, the spores germinate and resume their vegetative growth state. Since development is not essential to the viability of the cells under laboratory conditions, this process is amenable to genetic and molecular analysis.
There are currently two specific areas of investigation by our lab. First, we have discovered that all known developmental genes are dependent upon an intracellular protease for normal levels of their transcription. We are currently working to understand how this protease regulates gene transcription, and to identify the relevant protease substrate involved in this regulation. The gene encoding one substrate has been cloned that may act as a transcriptional repressor. We are also working to understand how proteolysis, or the effects of proteolysis, are regulated by the nutritional state of the cell. The protease itself is present throughout the life of the bacterium, yet the developmental effects are seen only upon nutrient limitation.
The second area of current study involves the determinants of cell fate within the fruiting body. Only about 20% of the cells that enter development are recovered as viable spores. We are trying to understand the factors that determine which cells will form spores, and whether the cells within the fruiting body that fail to sporulate have a specific role. We have learned that phase variation plays an essential role in establishing two populations of cells and that this is the basis of cell fate determination. We have isolated mutants that do not undergo phase variation, and so can establish only one of the two populations. These mutants are unable to complete sporulation, suggesting that each of the two populations of cells is required. We are currently asking whether the two populations have a different pattern of gene expression or a different spatial arrangement within the fruiting body.