Our research program seeks answers to a fundamental biological question:
How does an organism know when, where and for long to turn a gene on or off?
We address this question by investigating bacterial species
that establish intimate interactions with animal hosts.
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- PmrA-Regulated Lipid A Modifications, Regulation of and by the PmrA/PmrB System, and Control of Fe3+ Availability by PmrA-Dependent LPS Modifications
H. Deborah Chen, et al. PLoS Genet. 2011 July;7(7):e1002184
- Limited distribution of Y. pestis and S. enterica PhoP-activated genes across the Enterobacteriaceae family.
A–B. Matrices of conservation scores (CS) of proteins encoded by the genes directly activated by PhoP in Y. pestis (A) and S. enterica (B). CS is the BlastP score of the closest homologue in a particular species divided by the BlastP score of the protein against itself. CS values (represented by colors) can range from 0 when no homolog or ortholog is detected in another species, to 1 when the closest homolog exhibits 100% amino acid identity. The phylogenetic relationships shown to the left of the figures are based on orthologous housekeeping genes present in all species. Note that branch lengths do not represent phylogenetic distances.
- Differential control mediated by orthologous transcription factors.
Depiction of three related bacterial species (termed A, B and C) sharing an ancestral transcription factor, which regulates variable gene sets in the three organisms. Only two target genes (yellow and orange arrows) are shared among the three species. The remaining target genes are regulated by the transcription factor in only one of the species because the target gene(s) is species-specific (green and lavender arrows) or because only one of the species harbors binding sites for the transcription factor in the promoter region of genes shared across species (brown and blue arrows.) The shared target genes, constituting the core regulon, have two main roles: to cope with the environmental change that activates the regulon, and to control the amount of the active form of the transcription factor. By contrast, the species-specific targets aid each species to proliferate in the particular niches in which they live.
- Genetic regulatory architectures with positive feedback.
(a) Prototypic two-component signal transduction system. X – regulator protein, Y – sensor protein; x and y denote the corresponding genes, which are part of the same operon. Phosphorylated regulator binds with the genes’ autoregulated promoter and activates transcription. (b) The modular model of two-component signal transduction (redrawn from Ref. 6 with modifications). The phosphorylation module determines the concentration of X-P (phosphorylated regulator) as a function of the total sensor and regulator concentrations and the intensity of the activating stimulus. The autoregulation module defines the total sensor and regulator concentrations given the concentration of phosphorylated regulator. (c) A dynamic model of positive autoregulation introduced in Ref. 4. The regulator X (in phosphorylated form) can directly activate expression of its own gene.
- Expression of the Salmonella Mg2+ Transporter Gene mgtA Is Regulated by the PhoP/PhoQ System, the Rob Protein and by the mgtA LR.
When the sensor PhoQ detects low extracytoplasmic Mg2+, acid pH or antimicrobial peptides, it promotes phosphorylation of the PhoP protein, which binds to the mgtA promoter resulting in transcription initiation. Rob promotes mgtA transcription in response to a yet unidentified signal. Transcription elongation into the mgtA CR is regulated by the mgtA leader via a Mg2+-sensing riboswitch and by translation of an 18-codon proline-rich ORF designated mgtL. The mgtL ribosome binding site is denoted by RBS adjacent to a black line. Positions and sequences of stop codon mutations in the strains used in the experiments presented in Figure 4 are denoted below the linear mgtL RNA sequence. High Mg2+ and high proline conditions promote formation of stem-loop B, hindering transcription elongation into the mgtA CR. Low Mg2+ and/or low proline favor formation of stem-loop C, resulting in transcription of the mgtA CR. See also Figure S1.
- Table 1; Fig. S3) as described in Harari et al. (2010) and Zwir et al. (2005), where one sequence can belong to more than one cluster, and a subset of sequences can be hierarchically organized based on their specificity and sensitivity. A. Submotifs corresponding to the canonical direct repeat consensus sequence (S1). Three different subpatterns were identified within this class. B. Submotif S2 corresponding to a conserved variant in the first repeat sequence. C. Submotif S3 corresponding to a conserved variant in the second repeat sequence.