Research
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.
Visit our Research page for more information.
Reducing ribosome biosynthesis promotes translation during low Mg2+ stress.
Reducing ribosome biosynthesis promotes translation during low Mg2+ stress.
A cell maximizes its translation capacity by matching the rate of ribosome synthesis to the levels of ATO available for consumption. Here, we uncover a stress response pathway that supersedes this regulation and, unexpectedly, aids translation by decreasing ribosome production.
Schematic of the regulation of arabinan and arabinose utilization genes in B. thetaiotaomicron.
Schematic of the regulation of arabinan and arabinose utilization genes in B. thetaiotaomicron. Arabinan is extracellularly bound by two SusD-like proteins and imported into the periplasm by two SusC-like transporters. Large arabinan polymers are broken down into polymers of six to eight subunits in chain length (oligoarabinose) and eventually smaller arabino-oligosaccharides, such as arabinobiose, which are transported into the cytoplasm by AraP. These oligosaccharides are broken down to arabinose in the cytoplasm by an unknown glycoside hydrolase. Oligoarabinose binds to and activates the transcriptional regulator BT0366, which, in turn, promotes transcription of the arabinan utilization genes BT0365 to - 60 , BT0366 , and BT0367 to - 69 . L-Arabinose is transported into the cell by an unknown mechanism. Cytoplasmic arabinose prevents binding of the transcriptional repressor AraR to the promoters of the arabinan utilization gene BT0365 and the arabinose utilization gene BT0356 ( araM ). The transcriptional regulator BT4338 is necessary for full activation of arabinan and arabinose utilization genes. The signal controlling the activity of BT4338 is at present unknown. OM, outer membrane; IM, inner membrane.
Activation of the PhoP/PhoQ system by different signals.
Acidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence.
Activation of the PhoP/PhoQ system by different signals. Under non-inducing conditions, PhoQ promotes dephosphorylation of PhoP-P, thereby hindering transcription of PhoP-activated genes. Under inducing conditions (low extracytoplasmic Mg2+ levels, and/or presence of particular AMPs, and/or mild acidic pH), PhoQ enhances the levels of PhoP-P, thereby promoting transcription of PhoP-activated genes. Whereas the periplasmic domain of PhoQ detects low Mg2+ and AMPs, mildly acidic pH is sensed via the cytoplasmic domain.
Gene regulation by the transcription termination factor Rho.
Learning from the leaders: Gene regulation by the transcription termination factor Rho.
The RNA helicase Rho triggers 20–30% of transcription termination events in bacteria. While Rho is associated with most transcription elongation complexes, it only promotes termination of a subset. Recent studies of individual Rho-dependent terminators located within the 5′ leader regions of bacterial mRNAs have identified novel mechanisms that govern Rho target specificity and have revealed unanticipated physiological functions for Rho. In particular, the multistep nature of Rho-dependent termination enables regulatory input from determinants beyond the sequence of the Rho loading site, and allows a given Rho-dependent terminator to respond to multiple signals. Further, the unique position of Rho as a sensor of cellular translation has been exploited to regulate the transcription of genes required for protein synthesis, including those specifying Mg2+ transporters.
When Too Much ATP Is Bad for Protein Synthesis.
When Too Much ATP Is Bad for Protein Synthesis.
Cell's energy and protein synthesis potentials depend on the availability of Mg2+.
Bacteria sense and respond to various degrees of Mg2+ limitation.
Non-physiological increase in ATP disrupts essential Mg2+-dependent processes.
Cell restores free Mg2+ levels by shutting down synthesis of ATP and ribosomes.
Reciprocal Control between a Bacterium's Regulatory System and the Modification Status of Its Lipopolysaccharide.
The PmrA/PmrB regulatory system promotes modification of the bacterial cell surface.
Some of these modifications limit access of an inducing signal for the sensor PmrB.
A decrease in active regulator PmrA lowers expression of modifying determinants.
The activity of a regulatory system can change dynamically under inducing conditions.
Reducing ribosome biosynthesis promotes translation during low Mg2+ stress.
Reducing ribosome biosynthesis promotes translation during low Mg2+ stress.
A cell maximizes its translation capacity by matching the rate of ribosome synthesis to the levels of ATO available for consumption. Here, we uncover a stress response pathway that supersedes this regulation and, unexpectedly, aids translation by decreasing ribosome production.
