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Biology subjects

Kamino, K.

Publications and source records attributed to Kamino, K..

5 recordsLinked to original sources

E. coli do not count single molecules

Organisms use specialized sensors to measure their environments, but the fundamental principles that determine their accuracy remain largely unknown. In Escherichia coli chemotaxis, we previously found that gradient-climbing speed is bounded by the amount of information that cells acquire from their environment, and that E. coli operate near this bound. However, it remains unclear what prevents them from acquiring more information. Past work argued that E. colis chemosensing is limited by the physics of molecules stochastically arriving at cells receptors, without direct evidence. Here, we show instead that E. coli are far from this physical limit. To show this, we develop a theoretical approach that uses information rates to quantify how accurately behaviorally-relevant signals can be estimated from available observations: molecule arrivals for the physical limit; chemotaxis signaling activity for E. coli. Measuring these information rates in single-cell experiments across multiple background concentrations, we find that E. coli encode two orders of magnitude less information than the physical limit. Thus, E. coli chemosensing is limited by internal noise in signal processing rather than the physics of molecule diffusion, motivating investigation of what specific physical and biological constraints shaped the evolution of this prototypical sensory system.

biophysics↗

Sensory diversity and precise adaptation enable independent bet-hedging strategies for multiple signals at the same time

In uncertain environments, phenotypic diversity can be advantageous for survival. However, as the environmental uncertainty decreases, the relative advantage of having diverse phenotypes decreases. Here, we show how populations of E. coli integrate multiple chemical signals to adjust sensory diversity in response to changes in the prevalence of each ligand in the environment. Measuring kinase activity in single cells, we quantified the sensitivity distribution to various chemoattractants in different mixtures of background stimuli. We found that when ligands bind uncompetitively, the population tunes sensory diversity to each signal independently, decreasing diversity when the signal ambient concentration increases. However, amongst competitive ligands the population can only decrease sensory diversity one ligand at a time. Mathematical modeling suggests that sensory diversity tuning benefits E. coli populations by modulating how many cells are committed to tracking each signal proportionally as their prevalence changes.

systems biology↗

Optimal inference of molecular interactions in live FRET imaging

Intensity-based live-cell fluorescence resonance energy transfer (FRET) imaging converts otherwise unobservable molecular interactions inside cells into fluorescence time-series signals. However, inferring the degree of molecular interactions from these observables is challenging, due to experimental complications such as spectral crosstalk, photobleaching, and measurement noise. Conventional methods solve this inverse problem through algebraic manipulations of the observables, but such manipulations inevitably accumulate measurement noise, limiting the scope of FRET analysis. Here, we introduce a Bayesian inference framework, B-FRET, which estimates molecular interactions from FRET data in a statistically optimal manner. B-FRET requires no additional measurements beyond those routinely conducted in standard 3-cube FRET imaging methods, and yet, by using the information contained in the data more efficiently, dramatically improves the signal-to-noise ratio (SNR). We validate B-FRET using simulated data, and then apply it to FRET data measured from single bacterial cells, a system with notoriously low SNR, to reveal signaling dynamics that are otherwise hidden in noise.

biophysics↗

E. coli chemotaxis is information-limited

Organisms must acquire and use environmental information to guide their behaviors. However, it is unclear whether and how information quantitatively limits behavioral performance. Here, we relate information to behavioral performance in Escherichia coli chemotaxis. First, we derive a theoretical limit for the maximum achievable gradient-climbing speed given a cells information acquisition rate. Next, we measure cells gradient-climbing speeds and the rate of information acquisition by the chemotaxis pathway. We find that E. coli make behavioral decisions with much less than the 1 bit required to determine whether they are swimming up-gradient. However, they use this information efficiently, performing near the theoretical limit. Thus, information can limit organisms performance, and sensory-motor pathways may have evolved to efficiently use information from the environment.

biophysics↗

Generation And Attenuation Of Variability In A Bacterial Signalling Network Revealed By Single-Cell FRET

We present in vivo single-cell FRET measurements in the Escherichia coli chemotaxis system that reveal pervasive signaling variability, both across cells in isogenic populations and within individual cells over time. We quantify cell-to-cell variability of adaptation, ligand response, as well as steady-state output level, and analyze the role of network design in shaping this diversity from gene expression noise. In the absence of changes in gene expression, we find that single cells demonstrate strong temporal fluctuations. We provide evidence that such signaling noise can arise from at least two sources: (i) stochastic activities of adaptation enzymes, and (ii) receptor-kinase dynamics in the absence of adaptation. We demonstrate that under certain conditions, (ii) can generate giant fluctuations that drive signaling activity of the entire cell into a stochastic two-state switching regime. Our findings underscore the importance of molecular noise, arising not only in gene expression but also in protein networks.

systems biology↗