Kartik Subramanian to give the GBCB Seminar

Kartik Subramanian to give the GBCB Seminar

PhD student Kartik Subramanian will give the Genetics, Bioinformatics, and Computational Biology  (GBCB) seminar on Thursday September 19th at 4pm at the Virginia Bioinformatics Institute (VBI) Conference Center. The image is from Kartik’s paper (see Ref. 3 below).

caulobacter2

Here are more details:

Potential Role of a Bistable Histidine Kinase Switch in the Asymmetric Division Cycle of Caulobacter crescentus

Unlike other bacteria, Caulobacter crescentus exhibits distinct G1 and S phases during its asymmetric cell division cycle. A protein that plays an important role in the Caulobacter G1-to-S transition is PleC. PleC belongs to a class of bifunctional enzymes that can act as both phosphatase and kinase. In vitro experimental evidence indicates that the change in PleC function from phosphatase to kinase is brought about by none other that its own response regulator, DivK. Despite this interesting observation, PleC is believed to be primarily a phosphatase, while its kinase function is considered to have no in vivo significance. We have proposed a theoretical framework to explain the shift in PleC from a phosphatase to kinase. Our model is consistent with principles of detailed balance, allostery and enzyme-substrate interactions, and it is in reasonable agreement with experimental observations. We show that the change in PleC function from phosphatase to kinase is a bistable switch that lies at the heart of the G1-to-S transition. Furthermore, we use our model to tease out the differences between in vitro and in vivo experimental results and to propose that the kinase function of PleC is important for the proper progression of Caulobacter cells through the division cycle.

References:
1. Matroule J-Y, Lam H, Burnette DT, Jacobs-Wagner C (2004) Cytokinesis monitoring during development; rapid pole-to-pole shuttling of a signaling protein by localized kinase and phosphatase in Caulobacter. Cell 118: 579–590.

2. Paul R, Jaeger T, Abel S, Wiederkehr I, Folcher M, et al. (2008) Allosteric regulation of histidine kinases by their cognate response regulator determines cell fate. Cell 133: 452–461.

3.Subramanian K, Paul MR, Tyson JJ (2013) Potential Role of a Bistable Histidine Kinase Switch in the Asymmetric Division Cycle of Caulobacter crescentus. PLoS Comput Biol 9(9): e1003221.