A tale of two rhythms: Locked clocks and chaos in biology

Heltberg, Mathias L.; Krishna, Sandeep; Kadanoff, Leo P.; Jensen, Mogens H.

doi:10.1016/j.cels.2021.03.003

Cited by 31 publications

(32 citation statements)

References 118 publications

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“…Epiphenomenal, because rest of the reported oscillations at molecular levels (e.g., p38 MAPK oscillations, rhythms in p53 expression, NF-kB oscillations, etc.) were mostly observed under stress conditions ( Bar-Or et al, 2000 ; Hoffmann et al, 2002 ; Tomida et al, 2015 ), and to date, the precise role of their oscillatory expression remains equivocal ( Heltberg et al, 2021 ). Similarly, several other autonomous oscillations that were identified under physiological conditions (e.g., oscillatory activity of K+ channels in mouse embryos, p34 tyrosine phosphorylation cycles in sea urchin embryos, etc.)…”

Section: The Emerging Concept Of Autonomous Clocks and Their Mechanisms At Different Scales And Complexitiesmentioning

confidence: 99%

“…Although there are a number of ways and conditions that help phase-locking two or more biological cycles ( Heltberg et al, 2021 ), post-translational regulation of protein stability has emerged as a prominent target for an oscillator to couple another one. In this realm, the enzymatic ability to induce protein modifications (e.g., phosphorylation) with varying levels of potency and efficacy ( Holt et al, 2009 ; Swaffer et al, 2018 ; Swaffer et al, 2016 ; Ubersax et al, 2003 ) may elucidate how cell-cycle-driven proteolytic activities could couple cycles of cell divisions to peripheral biological cycles that are otherwise autonomous.…”

Section: The Logic and Potential Evolutionary Origins Of Autonomous Clocksmentioning

confidence: 99%

“…In a parameter space where axes represent the locking ratio p:q (of two interacting biological cycles) and the locking strength, various phases of coupling can emerge for different p:q values. This is because increasing the locking strength often increases the span of coupling for most plausible p:q ratios ( Heltberg et al, 2021 ), leading to potential overlaps between different p:q values (ergo the observation that they can coexist in the same cell population). This positive relationship between the locking strength and ratios, famously called the ‘Arnold Tongue,’ is a useful graphical tool to assess the conditions under which phase-locking can emerge.…”

Section: The Logic and Potential Evolutionary Origins Of Autonomous Clocksmentioning

confidence: 99%

“…Although an extended discussion of Arnold Tongues is beyond the scope of our piece, several other cases relating to phase-locking (e.g., mode hopping, period-doubling, chaos dynamics) can be qualitatively inferred from Arnold Tongues to explore underlying biological mechanisms. For further details, we refer our reader to a recent piece ( Heltberg et al, 2021 ) that summarizes this concept in ways that are fully accessible to the biologist.…”

Section: The Logic and Potential Evolutionary Origins Of Autonomous Clocksmentioning

confidence: 99%

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Autonomous clocks that regulate organelle biogenesis, cytoskeletal organization, and intracellular dynamics

Mofatteh

Iturra

Alamban

et al. 2021

eLife

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How do cells perceive time? Do cells use temporal information to regulate the production/degradation of their enzymes, membranes, and organelles? Does controlling biological time influence cytoskeletal organization and cellular architecture in ways that confer evolutionary and physiological advantages? Potential answers to these fundamental questions of cell biology have historically revolved around the discussion of ‘master’ temporal programs, such as the principal cyclin-dependent kinase/cyclin cell division oscillator and the circadian clock. In this review, we provide an overview of the recent evidence supporting an emerging concept of ‘autonomous clocks,’ which under normal conditions can be entrained by the cell cycle and/or the circadian clock to run at their pace, but can also run independently to serve their functions if/when these major temporal programs are halted/abrupted. We begin the discussion by introducing recent developments in the study of such clocks and their roles at different scales and complexities. We then use current advances to elucidate the logic and molecular architecture of temporal networks that comprise autonomous clocks, providing important clues as to how these clocks may have evolved to run independently and, sometimes at the cost of redundancy, have strongly coupled to run under the full command of the cell cycle and/or the circadian clock. Next, we review a list of important recent findings that have shed new light onto potential hallmarks of autonomous clocks, suggestive of prospective theoretical and experimental approaches to further accelerate their discovery. Finally, we discuss their roles in health and disease, as well as possible therapeutic opportunities that targeting the autonomous clocks may offer.

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Section: The Emerging Concept Of Autonomous Clocks and Their Mechanisms At Different Scales And Complexitiesmentioning

confidence: 99%

Section: The Logic and Potential Evolutionary Origins Of Autonomous Clocksmentioning

confidence: 99%

Section: The Logic and Potential Evolutionary Origins Of Autonomous Clocksmentioning

confidence: 99%

Section: The Logic and Potential Evolutionary Origins Of Autonomous Clocksmentioning

confidence: 99%

See 2 more Smart Citations

Autonomous clocks that regulate organelle biogenesis, cytoskeletal organization, and intracellular dynamics

Mofatteh

Iturra

Alamban

et al. 2021

eLife

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“…When two oscillators are coupled like this, one can expect to observe so-called p:q phase locking, meaning that p cycles of the cell cycle are completed for q cycles of the circadian clock. Whether such behavior indeed occurs depends on two factors [80]: (1) the relative frequencies of the circadian clock and the unforced cell cycle (i.e. the frequency in the absence of any circadian control, also called the natural frequency), and (2) on the strength of the coupling (here A cdk , i.e.…”

Section: Plos Computational Biologymentioning

confidence: 99%

A modular approach for modeling the cell cycle based on functional response curves

2021

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Modeling biochemical reactions by means of differential equations often results in systems with a large number of variables and parameters. As this might complicate the interpretation and generalization of the obtained results, it is often desirable to reduce the complexity of the model. One way to accomplish this is by replacing the detailed reaction mechanisms of certain modules in the model by a mathematical expression that qualitatively describes the dynamical behavior of these modules. Such an approach has been widely adopted for ultrasensitive responses, for which underlying reaction mechanisms are often replaced by a single Hill function. Also time delays are usually accounted for by using an explicit delay in delay differential equations. In contrast, however, S-shaped response curves, which by definition have multiple output values for certain input values and are often encountered in bistable systems, are not easily modeled in such an explicit way. Here, we extend the classical Hill function into a mathematical expression that can be used to describe both ultrasensitive and S-shaped responses. We show how three ubiquitous modules (ultrasensitive responses, S-shaped responses and time delays) can be combined in different configurations and explore the dynamics of these systems. As an example, we apply our strategy to set up a model of the cell cycle consisting of multiple bistable switches, which can incorporate events such as DNA damage and coupling to the circadian clock in a phenomenological way.

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Dissipative Systems

Wimberger

2022

Nonlinear Dynamics and Quantum Chaos

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A tale of two rhythms: Locked clocks and chaos in biology

Cited by 31 publications

References 118 publications

Autonomous clocks that regulate organelle biogenesis, cytoskeletal organization, and intracellular dynamics

Autonomous clocks that regulate organelle biogenesis, cytoskeletal organization, and intracellular dynamics

A modular approach for modeling the cell cycle based on functional response curves

Dissipative Systems

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