The alphaproteobacterial cell cycle lab
How do bacterial cells regulate cell cycle progression?
How are different cell types generated?
Our goal is to understand the cell cycle regulation design, using two powerful model species, Caulobacter crescentus and Sinorhizobium meliloti.
We aim to understand logic and principles of cell cycle regulation and asymmetrical cell division in different bacteria belonging to the alpha subdivision of proteobacteria, such as Caulobacter and Sinorhizobium (see figure below).
We are intensively working on these model systems as they asymmetrically divide and are sharing the same regulatory circuit however with significant differences (check Pini et al., 2013, Mol Micro and Pini et al., 2015, PLOS Genetics).
Several levels of regulation have been described, mostly in Caulobacter crescentus. The master regulator is CtrA (response regulator of Two-Component systems) that controls many important functions (motility, DNA methylation, cell division, chemotaxis, stalk and pili biogenesis) and blocks directly the origin of DNA replication.
Multiple regulatory levels that are important for CtrA control:
- phosphorylation by CckA and ChpT (Biondi et al., 2006, Nature) blocked by the DivJ-(PleC)-DivK module and c-di-GMP
- ClpXP-mediated degradation controlled by RcdA, PopA, CpdR activated by the DivJ-(PleC)-DivK module and c-di-GMP
- transcriptional regulation by CcrM-dependent DNA methylation, DnaA, GcrA (Fioravanti et al., 2013, PLOS Genetics)