Investigating signaling mechanisms in Caulobacter crescentus

How bacteria control their shape and division was one of the first topics investigated with molecular biology, and many unanswered questions remain today. This dissertation research used the model organism Cualobacter crescentus to investigate how phospho-signaling controls asymmetric cell division, and how those signals are initiated and regulated. Most signaling in bacteria is achieved through two component systems (TCS), which are comprised of a histidine kinase and a response regulator. The downstream effects of response regulator activation have been well documented and can affect gene transcription, protein interactions or enzyme activity. However, very little is known about how histidine kinases are activated. Caulobacter uses TCS to control its asymmetric cell division and differentiation, but the events that initiate the cell cycle and the ability of an outside signal to impinge upon cell cycle progression remain unknown.Using three different methods, I have been able to shed light on signaling and cell cycle progression in Caulobacter crescentus. I have developed a tool to determine which proteins and conditions activate histidine kinases. I have shown that an outside environmental signal can feed into the TCS controlling cell cycle progression. I have also shown that a protein similar to a eukaryotic tyrosine phosphatase controls membrane integrity and morphology and is essential for viability in Caulobacter