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Revision as of 08:35, 6 August 2018
Project Background
In 2017, the Nobel Prize in Physiology or Medicine was awarded jointly to three Americans – Jeffrey Hall, Michael Rosbash and Michael Young – for their discoveries of molecular mechanisms controlling the circadian rhythm[1], which focused the public attention on the concept circadian once again . Circadian exists ubiquitously across the tree of life, regulating metabolic and behavioral changes in anticipation of day-night variations in environmental conditions[2]. Since the 4th century, when Androsthnenes[3] observed the diurnal and nocturnal variation in the movement of tamarind trees, the human race has never ceased to explore the mystery of circadian rhythm although the systematical study started only several decades ago. Today, we acquire the knowledge that cell-autonomous time-keeping system could be categorized into two types according to different clock mechanisms.
Clock Mechanisms I: Transcription-Translation Feedback Loops
Transcription-Translation Feedback Loops（TTFL）mechanisms demonstrated that mRNA and protein oscillations control the anticipated behavioral changes of organisms. For example, in Neurospora crassa, transcription of the Frq gene is driven by the White Collar (WC) complex, comprised of the proteins Wc1 and Wc2. Subsequently, the FRQ protein interacts with RNA helicase, FRH, and this complex represses Frq transcription. The blue-light photoreceptor Vvd , which acts similarly to Drosophila Cry to promote clock protein degradation and modulate transcription, will interacts with both the repressing FRQ/FRH complex and the positive WC complex[4]. Today, the principle of TTFL is considered to be a universal bio-brick of circadian clocks and has been identified in all model systems studied to date[4].
Clock Mechanisms II:Post-translational Feedback Loops
Apart from the regulation of transcripts and proteins, multiple circadian post-translational modifications of some components such as acetylation, methylation, sumoylation, and phosphorylations also proved to play important roles in circadian system or otherwise act as clocks themselves. A good example of this mechanism is the KaiABC oscillation system in the cyanobacteria. Oscillations are controlled by phosphorylation of the KaiC protein, which is modulated by the KaiA and KaiB proteins[5]. This mechanism is also used in the 2018 Tianjin iGem project and will be illustrated extensively in other pages.