Team:Newcastle/Bistability in B.Subtilis

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Bistability in B.subilis

The positive feedback in comK regulation provides the bistability in B. subtilis. we can either knock out the competence system in B. subtilis or use a homolog system from another bacteria.

[http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2041856&blobname=NIHMS25553-supplement-01.pdf ClustalW aligment of comK genes] (Figure 2)

  • Streptococcus pneumoniae:

There is no evidence of bistability in in pneumococcal competence so we can not use the genes from S.pneumoniae (http://dx.doi.org/10.1038/nrmicro1613 )

  • H. influenzae

Again, nearly all the cells become competent. (http://dx.doi.org/10.1016/0168-9525(96)10014-7)

  • B. cereus

It has two homologues of B. subtilis comK gene. comK1(BC1134, 62%), comK2(BC5250, 48%). But the regulation and function of these two comK genes are unknown. B. cereus showd competence when comK gene from B. subtilis is placed into B. cereus (http://gbb.eldoc.ub.rug.nl/root/2008/MicrobBiotnMironczuk/)

Mathematical Modelling of comK

-[http://www.nature.com/nature/journal/v440/n7083/full/nature04588.html An excitable gene regulatory circuit induces transient cellular differentiation]

-[http://www.nature.com/nature/journal/v440/n7083/extref/nature04588-s1.pdf And its supplementary information with math equations and parameters]

  • Related Links:
  1. [http://www3.interscience.wiley.com/cgi-bin/fulltext/118659803/HTMLSTART Bistability using positive autoregulation of ComK]
  2. [http://www.ncbi.nlm.nih.gov/pubmed/8878039 Regulatory inputs for the synthesis of ComK]
  3. [http://mic.sgmjournals.org/cgi/content/full/152/2/473 Functional analysis of the competence transcription factor ComK of Bacillus subtilis by characterization of truncation variants]

[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2041856#SD2 ClustalW aligment of comK genes]

Sigma D

It was porposed that perhaps sigma D could be used to make a stochastic switch however perhaps not enough is known about how it is regulated?

The factors that are responsible for the stationary-phase elevation in sigD levels are unknown. sigD-dependent transcription declines after the onset of sporulation, and inactivation of sigD itself causes no overt defect in sporulation, therefore sigD’s contribution to sporulation, if any, is modest. Present evidence demonstrates that sigD is primarily involved in the expression of flagellar, motility, and autolysin genes and their regulators.

The Sigma Factors of Bacillus subtilis, WILLIAM G. HALDENWANG MICROBIOLOGICAL REVIEWS, Mar. 1995, p. 1–30

Synthetic Switches

Synthetic bistable toggle switches constructed from LacI and Cl repressors can also be used. Theese repressors repress each other creating a bistable switch with two negative feedback loops. Bistable switch with two positive feedback can also be considered.

Some useful links for bistability

  • [http://dx.doi.org/10.1016/S0955-0674(02)00314-9 Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability]
  • [http://www3.interscience.wiley.com/cgi-bin/fulltext/118630112/HTMLSTART Bistability in Bacteria]
  • [http://www3.interscience.wiley.com/journal/118659872/abstract?CRETRY=1&SRETRY=0 Initiation of sporulation]
  • [http://www.sciencemag.org/cgi/content/full/320/5872/65 Stochasticity and Cell Fate]



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