Our Research

The Microbial Development group studies development in the model organism Bacillus subtilis, which involves metamorphosis of the rod-shaped vegetative cell into a dormant, highly resistant spore.

At its onset, the cells abandon medial (symmetrical) cell division, and switch to a mode of polar (asymmetric) division, which gives rise to a dissimilar progeny, the mother cell and the smaller prespore (figure below).

The prespore will differentiate into the mature spore, whereas the mother cell eventually lysis to release the spore (see figure). Polar division is served by a specialized mode of chromosome segregation that ensures that one of the replicated chromosomes is partitioned into the prespore, while the other stays in the mother cell (see the figure below), and one project in the laboratory deals with the coordination between asymmetric division and chromosome segregation.

Gene expression in the prespore and the mother cell is then orchestrated by a cascade of RNA polymerase sigma subunits, which are activated in a cell type-specific manner, in response to the course of morphogenesis and as the result of cell-cell signaling pathways that link the two lines of gene expression.

The group is also investigating a pathway by which the mother cell induces activation of the late prespore-specific sigma factor. It functions only after the complete engulfment of the prespore by the mother cell (see figure), and involves a novel type of synapse-like complex that connects the two cells, as well as a new mechanism for maintaining the polymerase in the prespore inactive until the appropriate signal is perceived.

Keeping the programs of gene expression in the two cells in close register with the course of morphogenesis allows the temporal differentiation of classes of gene expression, whose proper deployment is important for the fidelity of morphogenesis. In a dramatic example, heterochronic mutants, in which an early morphogenetic gene (cotE) is transplanted to late classes of expression, show suppressed morphogenesis of a spore protective layer.

In addition, and importantly, much of the differentiation process relies on the sub-cellular localization of proteins, and the group is also interested on the mechanisms by which proteins are targeted to their final addresses. An example is the localization of an integral membrane protein required for cortex biogenesis, a layer of peptidoglycan that confers heat resistance to the spore (see figure). Lastly, knowledge is also being translated into research with a more applied angle, from the use of spores as display systems for bioactive molecules, to the characterization of spore-formers with a potential use as probiotics.