ROD-SHAPING PROTEINS · Discovery and characterization of factors coupling the cytoskeleton to cell wall biogenesis in Bacillus subtilis

The bacterial cell wall is a crucial structure designed to provide physical integrity to the cell. The cell wall (CW) defines the shape of most bacterial cells and it must be a dynamic structure, being continuously synthesized and remodeled to enable several physiological and morphological changes. A number of genes involved in cell shape control have been identified in rod-shaped bacteria, including genes implicated in cell wall synthesis or assembly. It has been recently discovered that the mreB family of genes encode structural and functional homologues of eukaryotic actin (Jones, et al. 2001; van de Ent, et al. 2001). Bacillus subtilis contains three MreB family members, MreB, Mbl and MreBH, which undergo ATP-dependent polymerization into helical structures co-localized around the cell periphery, close to the inner surface of the cytoplasmic membrane. These filamentous structures play a direct role in determining cell shape in non-spherical bacteria (Carballido-López and Errington, 2003; Jones, et al. 2001) and also in a range of various other important cell processes, including chromosome segregation and cell polarity. However, the different functions of the MreB isoforms and their effector proteins remained unknown. There are several kind of proteins that they could interact with in order to exert spatial and temporal control over CW synthesis. The main goals of this research proposal are the following: 1. Identification of new genes involved in lateral cell wall synthesis in B. subtilis and their relationships with the MreB homologues. 2. To characterize biochemical and genetically the interactions of MreB isoforms with the different effector proteins. 3. To investigate the functional significance of those interactions on cell processes including cell wall elongation and cell division.