Memeli sirkadiyen saatinin yeni bileşenlerinin saptanması

The circadian clock is a biological timing system that oscillates with a period of 24 hours and is coordinated with the day-night cycle. Since a wide array of physiological and behavioral processes are regulated by the circadian clock, understanding the molecular clockwork will help develop treatments against various clock-related health problems including obesity, jetlag, insomnia, and psychological disorders. The molecular mechanism of the circadian clock has been extensively studied during the last decade, and consequently, numerous core clock components and clock modifiers have been identified so far. Yet, the clock mechanism is not entirely solved. There is a great competition among researchers for discovery of novel clock components, and one of the mostly commonly used methods on this purpose is the naive Bayesian strategy. In this thesis work, high probability clock genes identified by the naive Bayesian strategy were experimentally screened through mammalian two-hybrid assay system for likely interactions with the core clock components. The entire screen yielded two hits, leptin receptor overlapping transcript-like 1 (Leprotl1) and sterol O-acyltransferase 1 (SOAT1), and both of them have metabolic functions. LEPROTL1 appears to interact with both mCRY1 and mCRY2, while SOAT1 interacts with only mCRY1. Herein, the involvement of Leprotl1 in the circadian clockwork was investigated. It was shown that depletion of Leprotl1 resulted in damped amplitude, long-period and phase advance phenotypes of the oscillations in cell lines, suggesting a role of Leprotl1 in the proper functioning of the timing system.