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Cluzel, P.

Publications and source records attributed to Cluzel, P..

2 recordsLinked to original sources

Pulsating transcriptional dynamics generates cell-to-cell variability in E. coli flagellum synthesis

The classic picture of flagellum biosynthesis in E. coli, inferred from population measurements, describes a tightly controlled, deterministic transcriptional program. In individual E. coli cells, we discover that flagellar promoters are in fact stochastically activated in pulses. Such pulses comprise coordinated on and off states of promoter activity, each of which can span multiple generations. We demonstrate that this pulsing program obeys the regulatory logic of flagellar assembly, which dictates whether some promoters skip pulses. Remarkably, pulses in this transcriptional network appear to be actually governed by a post-translational circuit. Our results suggest that even topologically simple transcriptional networks can generate unexpectedly rich temporal dynamics and phenotypic heterogeneities.

microbiology

Codon-dependent noise dictates cell-to-cell variability in nutrient poor environments

Under nutrient-rich conditions, stochasticity of transcription drives protein expression noise. However, by shifting the environment to amino acid-limited conditions, we identified in E. coli a source of noise whose strength is dictated by translational processes. Specifically, we discovered that cell-to-cell variations in fluorescent protein expression depend on codon choice, with codons yielding lower mean expression after amino acid downshift also resulting in greater noise. We propose that ultra-sensitivity in the tRNA charging/discharging cycle shapes the strength of the observed noise by amplifying fluctuations in global intracellular parameters, such as the concentrations of amino acid, synthetase, and tRNA. We hypothesize that this codon-dependent noise may allow bacteria to selectively optimize cell-to-cell variability in poor environments without relying on low molecular numbers.

systems biology