Noise and delay can shape distribution functions in stochastic reaction dynamics

Bhadana, Jyoti; Chanu, Athokpam Langlen; Malik, Md. Zubbair

doi:10.1007/s11071-021-06643-5

Cited by 3 publications

(4 citation statements)

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“…Noise is an inherent property associated with the dynamics of any natural system ( Glass, 2001 ; Bhadana et al, 2019 , 2021 ). We studied the dynamics of

for four possible configurational interactions of CK2 with the cytosolic PER proteins

as we did in the previous simulation by keeping

fixed at

(which is associated with regular pattern of active circadian rhythm), and changing the strength of the noise

with four values for

and

( Figure 6 ).…”

Section: Resultsmentioning

confidence: 99%

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Disruption in the regulation of casein kinase 2 in circadian rhythm leads to pathological states: cancer, diabetes and neurodegenerative disorders

Malik

Dashti

Fatima

et al. 2023

Front. Mol. Neurosci.

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IntroductionCircadian rhythm maintains the sleep–wake cycle in biological systems. Various biological activities are regulated and modulated by the circadian rhythm, disruption of which can result in onset of diseases. Robust rhythms of phosphorylation profiles and abundances of PERIOD (PER) proteins are thought to be the master keys that drive circadian clock functions. The role of casein kinase 2 (CK2) in circadian rhythm via its direct interactions with the PER protein has been extensively studied; however, the exact mechanism by which it affects circadian rhythms at the molecular level is not known.MethodsHere, we propose an extended circadian rhythm model in Drosophila that incorporates the crosstalk between the PER protein and CK2. We studied the regulatory role of CK2 in the dynamics of PER proteins involved in circadian rhythm using the stochastic simulation algorithm.ResultsWe observed that variations in the concentration of CK2 in the circadian rhythm model modulates the PER protein dynamics at different cellular states, namely, active, weakly active, and rhythmic death. These oscillatory states may correspond to distinct pathological cellular states of the living system. We find molecular noise at the expression level of CK2 to switch normal circadian rhythm to any of the three above-mentioned circadian oscillatory states. Our results suggest that the concentration levels of CK2 in the system has a strong impact on its dynamics, which is reflected in the time evolution of PER protein.DiscussionWe believe that our findings can contribute towards understanding the molecular mechanisms of circadian dysregulation in pathways driven by the PER mutant genes and their pathological states, including cancer, obesity, diabetes, neurodegenerative disorders, and socio-psychological disease.

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“…Noise is an inherent property associated with the dynamics of any natural system ( Glass, 2001 ; Bhadana et al, 2019 , 2021 ). We studied the dynamics of

for four possible configurational interactions of CK2 with the cytosolic PER proteins

as we did in the previous simulation by keeping

fixed at

(which is associated with regular pattern of active circadian rhythm), and changing the strength of the noise

with four values for

and

( Figure 6 ).…”

Section: Resultsmentioning

confidence: 99%

“…Noise is an inherent property associated with the dynamics of any natural system (Glass, 2001;Bhadana et al, 2019Bhadana et al, , 2021. We studied the dynamics of P N for four possible configurational interactions of CK2 with the cytosolic PER proteins ( , P 1 P P P P , and 500 (Figure 6).…”

Section: Noise Can Regulate the Circadian Statesmentioning

confidence: 99%

Disruption in the regulation of casein kinase 2 in circadian rhythm leads to pathological states: cancer, diabetes and neurodegenerative disorders

Malik

Dashti

Fatima

et al. 2023

Front. Mol. Neurosci.

Self Cite

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“…Delayed regulation has been implicated in the p53 (37) and Hes1 systems (38). Delay has been described as a regulatory motif in its own right capable of modulating, suppressing, and buffering noise (39)(40)(41)(42), even beyond Markovian limits (41,42), as well as inducing oscillations (37,(42)(43)(44).…”

Section: Introductionmentioning

confidence: 99%

“…Delayed regulation has been implicated in the p53 (Liu et al, 2011) and Hes1 systems (Barrio et al, 2006). Delay has been described as a regulatory motif in its own right, capable of modulating, suppressing, and buffering noise (Bhadana et al, 2021, Gedeon and Bokes, 2012, Singh et al, 2021, Zhang and Zhou, 2019), even beyond Markovian limits (Bhadana et al, 2021, Singh et al, 2021), as well as inducing oscillations (Bratsun et al, 2015, Liu et al, 2011, Miekisz et al, 2011, Singh et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Transient and delay chemical master equations

Gorin

Yoshida

Pachter

2022

Preprint

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The serial nature of reactions involved in the RNA life-cycle motivates the incorporation of delays in models of transcriptional dynamics. The models couple a bursty or switching promoter to a fairly general set of Markovian or deterministically delayed monomolecular RNA interconversion reactions with no feedback. We provide numerical solutions for the RNA copy number distributions the models induce, and solve several systems with splicing and degradation. An analysis of single-cell and single-nucleus RNA sequencing data using these models reveals that the kinetics of nuclear export do not appear to require invocation of a non-Markovian waiting time.

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