Fold-change detection in biological systems

Adler, Miri; Alon, Uri

doi:10.1016/j.coisb.2017.12.005

Cited by 90 publications

(117 citation statements)

References 64 publications

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“…In fact, the interconnections between the pr-AMG RNs and the AMPAR-expressing prRNs (black arrow Figure 8; see also sFig.1a), are suggestive of an incoherent feedforward loop [43]. We have already documented that Ciona larvae are able to phototax in a wide range of illumination conditions [17], and moreover, we have found that Ciona larvae show robust fold-change detection [44] behavior (manuscript in preparation). Together these observations suggest that the RN cluster plays a role in visual processing, rather than simply passing information to the MG.…”

Section: Figure 8 Models Showing Parallel Visuomotor Pathways For Nementioning

confidence: 66%

Parallel Visual Circuitry in a Basal Chordate

Kourakis¹,

Borba²,

Zhang³

et al. 2019

Preprint

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A common CNS architecture is observed in all chordates, from vertebrates to basal chordates like the ascidian Ciona. Currently Ciona stands apart among chordates in having a complete larval CNS connectome. Starting with visuomotor circuits predicted by the Ciona connectome, we used expression maps of neurotransmitter use with behavioral assays and pharmacology to identify two parallel visuomotor circuits that are responsive to different components of visual stimuli. The first circuit is characterized by glutamatergic photoreceptors and responds to the direction of light. These photoreceptors project to cholinergic motor neurons, via two tiers of cholinergic interneurons. The second circuit is responsive to changes in ambient light and mediates an escape response. This circuit starts with novel GABAergic photoreceptors which project to GABAergic interneurons, and then to cholinergic interneurons shared with the first circuit. Our observations on neurotransmitter use and the behavior of larvae lacking photoreceptors indicate the second circuit is disinhibitory.

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Section: Figure 8 Models Showing Parallel Visuomotor Pathways For Nementioning

confidence: 66%

Parallel Visual Circuitry in a Basal Chordate

Kourakis¹,

Borba²,

Zhang³

et al. 2019

Preprint

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“…Several biochemical circuit responses and many aspects of perception scale logarithmically 5 . A robust and generic pattern of this sort seems likely to depend on a robust and generic underlying design.…”

Section: Resultsmentioning

confidence: 99%

A biochemical logarithmic sensor with broad dynamic range

Frank

2018

F1000Res

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Sensory perception often scales logarithmically with the input level. Similarly, the output response of biochemical systems sometimes scales logarithmically with the input signal that drives the system. How biochemical systems achieve logarithmic sensing remains an open puzzle. This article shows how a biochemical logarithmic sensor can be constructed from the most basic principles of chemical reactions. Assuming that reactions follow the classic Michaelis-Menton kinetics of mass action or the more generalized and commonly observed Hill equation response, the summed output of several simple reactions with different sensitivities to the input will often give an aggregate output response that logarithmically transforms the input. The logarithmic response is robust to stochastic fluctuations in parameter values. This model emphasizes the simplicity and robustness by which aggregate chemical circuits composed of sloppy components can achieve precise response characteristics. Both natural and synthetic designs gain from the power of this aggregate approach.

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“…Our analyses to test for Weber-Fechner law assume that each cell performs baseline-normalization. This could give an extra benefit by reducing variability among cells 66,[75][76][77] . However, cells need time to establish a baseline between successive glucose-additions, since shortening the period between glucose additions no longer gave scaling of the cAMP peak height with the relative fold change (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…3B). Because systems that detect relative changes add up inputs with positive and negative responses 66 , we also tested the application of two such inputs simultaneously. First, we identified salt stress as a negative input as this reduced cAMP levels transiently (Fig.…”

Section: Engineering Of a Versatile Epac Sensor For Camp Quantificatimentioning

confidence: 99%

A yeast FRET biosensor enlightens cAMP signalling

Botman

O’Toole²,

Goedhart

et al. 2019

Preprint

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The cAMP-PKA signalling cascade in budding yeast regulates adaptation to changing environments. Many questions remain about the function of cAMP dynamics, largely because no robust method for in vivo cAMP measurements exists for yeast. Here we developed yEPAC, a FRET-based biosensor for cAMP measurements in yeast. We show that this biosensor can be used in flow cytometry, allowing for highthroughput single cell-level quantification that complements microscopy measurements. We quantified both steady-state cAMP levels and dynamic changes in response to sudden nutrient transitions. Steadystate cAMP levels were found to correlate with growth rate (rather than glycolytic flux) and were independent of extracellular sensing. During transitions, a cAMP-peak differentiates between different carbon source transitions, and is generated only when switching from non-or slowly-fermentable sugars to rapidly fermentable ones. Furthermore, generation of the cAMP peak is mediated by a combination of extracellular sensing and metabolism; deficits in either results in a largely diminished response. Moreover, the cAMP peak follows Weber's law; its height scales with the relative, and not the absolute, change in glucose. This means that cells respond to small changes in extracellular glucose when the initial level is low, but ignore these changes when this level is high. Lastly, we speculate that the cAMP peak height conveys information about prospective growth rates, especially for fermentable sugars. In conclusion, our yEPAC-sensor makes possible new avenues for understanding yeast physiology, signalling and metabolic adaptation.

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Fold-change detection in biological systems

Cited by 90 publications

References 64 publications

Parallel Visual Circuitry in a Basal Chordate

Parallel Visual Circuitry in a Basal Chordate

A biochemical logarithmic sensor with broad dynamic range

A yeast FRET biosensor enlightens cAMP signalling

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