The cells of multicellular organisms are different from each other, but they all derive from identical progenitor cells, which transform into different cell types during the development of the organism. This process of “cellular differentiation” is responsible for the formation of all our body parts, of our bones, our skin, our brain, our blood. Cellular differentiation depends on the production of specific “differentiation” machineries in the cell that mediate these transformations. Cells also need to maintain general “housekeeping” machineries for the metabolic functions that are necessary for survival, such as the acquisition of nutrients, the production of energy, and the maintenance of their genetic material. How “differentiation” machineries and “housekeeping” machineries interact to mediate the transformation of one cell type into another is not well understood. This is due largely to the fact that it is difficult to interfere with housekeeping machineries in complex organisms without killing the cells, so studies have typically focused on differentiation-specific machineries only.
Bacteria provide terrific systems for studying the interplay between housekeeping metabolism and differentiation. They have streamlined and easily manipulated cellular machineries and a minimal number of essential genes. Many bacterial species embark upon relatively simple differentiation processes that culminate in the formation of specific cell types. In this project, we aim to provide a comprehensive analysis of the role of housekeeping metabolism during endospore formation in the bacterium Bacillus subtilis. Sporulation is a simple differentiation process that entails the interaction between two cells arising from a single cell division: the forespore, which becomes a metabolically dormant spore that is virtually immortal, and the mother cell, which dies after sporulation. We have developed a system to eliminate specific housekeeping machineries in only the mother cell or the forespore during sporulation. This system enables us to define which housekeeping functions are important during sporulation, and in which cell. We are using this system, in combination with a variety of cutting-edge technologies, to obtain a detailed understanding of the role of housekeeping metabolism in sporulation. We expect that our results will provide insights into the metabolic processes that underpin cellular differentiation.
