Dissertations. Paper 1171. Building And Mining An Atlas Of The Mammalian Circadian

Nearly all mammals possess internal clocks that synchronize with the day-night cycles of their environments. These circadian clocks help temporally segregate competing or incompatible physiological processes to anticipated appropriate times of the day. As the mammalian clock system is principally regulated by transcription factors, numerous previous studies have sought to characterize gene-transcript oscillations as a primary means of gaining insight into what pathways are controlled by the clock. However, most studies have only examined one or two specific tissue types at a time, often with suboptimal sampling resolution. Little work has been done to analyze clock control at the organism level. Furthermore, despite the apparent importance of circadian rhythms in nearly all major physiological processes, actionable medical knowledge has been difficult to extract. This lack of translational insight is not due to a simple lack of data, but rather to gaps in assembling a big picture from scattered data and to deficiencies in analytical methods. The goal of this dissertation was to overcome these shortcomings by forging a comprehensive atlas of the mammalian circadian transcriptome. High-throughput techniques were used to identify circadian transcript rhythms at a high sampling resolution in twelve different organs. This work brought to light critical systemic roles of the mammalian circadian clock at the organism level, while providing a blueprint for futur