Over the years my research focused on the molecular mechanism of essential processes that take place in the bacterial cell envelope. In particular we studied the membrane-bound enzymes involved in the lipoprotein modification pathway in great detail. We addressed questions on membrane topology, enzymatic activity, substrate specificity and the mechanism of the reactions. Our work contributed to a better understanding of how proteins become fatty-acid acylated and led to research projects on the development of vaccine candidates and screening for novel antibacterial agents.
CELL SHAPE DYNAMICS
My second project involves the bacterial cell wall that is essential for bacterial viability and that gives bacteria their shape. The cell wall is a dynamic macromolecular structure. During cell elongation and cell division, new building blocks are incorporated and old components are recycled to allow cells to grow and replicate. Cell shape itself is also highly dynamic. Depending on the growth conditions and the environment bacteria can undergo shape transitions, both on short-term and on evolutionary time scale. We are interested in understanding how the cell wall contributes to these shape transitions and how cell shape influences virulence. We use the bacterium Helicobacter pylori as a model system. The lab demonstrated that H. pylori undergoes a morphological transition from spiral-rod to coccoid as a mechanism to escape the innate immune system and that maintenance of the spiral-rod shape is essential for its survival in its unique niche, the stomach. The involvement of various cell wall hydrolases was demonstrated. We use a combination of bacterial genetics, biochemistry and cellular microbiology to identify protein networks and their regulation implicated in cell shape dynamics.