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Circadian clocks play a pivotal role in orchestrating numerous physiological and developmental events. Waveform shapes of the oscillations of protein abundances can be informative about the underlying biochemical processes of circadian clocks. We derive a mathematical framework where waveforms do reveal hidden biochemical mechanisms of circadian timekeeping. We find that the cost of synthesizing proteins with particular waveforms can be substantially reduced by rhythmic protein half-lives over time, as supported by previous plant and mammalian data, as well as our own seedling experiment. We also find that previously-enigmatic, cyclic expression of positive arm components within the mammalian and insect clocks allows both a broad range of peak time differences between protein waveforms and the symmetries of the waveforms about the peak times. Such various peak-time differences may facilitate tissue-specific or developmental stage-specific multicellular processes. Our waveform-guided approach can be extended to various biological oscillators, including cell-cycle and synthetic genetic oscillators.
The generation of two non-identical membrane compartments via exchange of vesicles is considered to require two types of vesicles specified by distinct cytosolic coats that selectively recruit cargo and two membrane-bound SNARE pairs that specify fus
In mammals, most cells in the brain and peripheral tissues generate circadian (~24hr) rhythms autonomously. These self-sustained rhythms are coordinated and entrained by a master circadian clock in the suprachiasmatic nucleus (SCN). Within the SCN, t
Generation of mechanical oscillation is ubiquitous to wide variety of intracellular processes. We show that catchbonding behaviour of motor proteins provides a generic mechanism of generating spontaneous oscillations in motor-cytoskeletal filament co
We propose a multiscale chemo-mechanical model of cancer tumour development in an epithelial tissue. The model is based on transformation of normal cells into the cancerous state triggered by a local failure of spatial synchronisation of the circadia
There is a widening recognition that cancer cells are products of complex developmental processes. Carcinogenesis and metastasis formation are increasingly described as systems-level, network phenomena. Here we propose that malignant transformation i