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Title: Molecular analysis of the circadian clock in mammals
Author: Field, M. D.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2000
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The majority of organisms on Earth, from cyanobacteria upwards, contain an internal timing mechanism that allows them to make optimum use of the rhythmic abundance of many environmental resources (e.g. sunlight). In mammals, the master circadian (i.e. daily) clock is contained within the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The clock is thought to consist, at the simplest level, of a number of autoregulatory negative feedback loops involving the products of the cryptochrome (mCry1 and mCry2) and period (mPer1, mPer2 and mPer3) genes. These loops are driven by the positive factors encoded by the clock and Bmal 1 genes. Chapter 3 of this dissertation presents immunocytochemical data showing that the expression of mPER1 and mPER2 protein is rhythmic in the SCN, both in mice entrained to a light-dark cycle or in continuous darkness. In contrast, the expression of mTIM is constitutive under all lighting conditions. These are thus functional differences in gene expression between mice and the fruitfly Drosophila, where tim is a central, rhythmic clock component. The clock can be reset (i.e. phase advanced or delayed) by light incident on the retina during the night. Experimental data, both in vivo and in vitro, suggest that mCry genes are central oscillator components insensitive to light, whereas mPer1 and mPer2 are up-regulated by resetting light pulses. Resetting by light pulses which delay the clock occurs rapidly (within 1-2 cycles), whereas the full expression of advances of the clock can take several cycles to be completed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available