Abstract
Autonomous endogenous time-keeping is ubiquitous across many living organisms, known as the circadian clock when it has a period of about 24 h. Interestingly, the fundamental design principle with a network of interconnected negative and positive feedback loops is conserved through evolution, although the molecular components differ. Filamentous fungus Neurospora crassa is a well-established chrono-genetics model organism to investigate the underlying mechanisms. The core negative feedback loop of the clock of Neurospora is composed of the transcription activator White Collar Complex (WCC) (heterodimer of WC1 and WC2) and the inhibitory element called FFC complex, which is made of FRQ (Frequency protein), FRH (Frequency interacting RNA Helicase) and CK1a (Casein kinase 1a). While exploring their temporal dynamics, we investigate how limit cycle oscillations arise and how molecular switches support self-sustained rhythms. We develop a mathematical model of 10 variables with 26 parameters to understand the interactions and feedback among WC1 and FFC elements in nuclear and cytoplasmic compartments. We performed control and bifurcation analysis to show that our novel model produces robust oscillations with a wild-type period of 22.5 h. Our model reveals a switch between WC1-induced transcription and FFC-assisted inactivation of WC1. Using the new model, we also study the possible mechanisms of glucose compensation. A fairly simple model with just three nonlinearities helps to elucidate clock dynamics, revealing a mechanism of rhythms’ production. The model can further be utilized to study entrainment and temperature compensation.
Highlights
The Earth’s rotation around its own axis gives rise to the 24-h day and night cycles
The core negative feedback loop of the clock of Neurospora is composed of the transcription activator White Collar Complex (WCC) and the inhibitory element called FFC complex, which is made of FRQ (Frequency protein), Frequency-interacting Helicase (FRH) (Frequency interacting RNA Helicase) and Casein Kinase-1a (CK1a) (Casein kinase 1a)
We study the possible mechanisms of glucose compensation
Summary
The Earth’s rotation around its own axis gives rise to the 24-h day and night cycles. To anticipate these daily environmental changes in light and temperature, life in all its kingdoms has evolved a time-keeping molecular machinery [1,2,3]. In order to understand the basic clock mechanisms, we study a filamentous fungus, Neurospora crassa (N. crassa) [7]. Their natural habitats are soils, plants, trees, and food resources [8]. An example is the production of ethanol from xylose derived from plant dry matter biomass (lignocellulosic substrates). The xylan to ethanol pathway has been found to be clock regulated at each stage [9]
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