Prof. Dr. Aziz Sancar Biological Clock Lab @Gebze Technical University (GTU)

Interested students might contact the PI at any time by sending a transcript and CV (nuriozturk [at]  gtu.edu.tr)

Lab Members  

E-mail: nuriozturk13 [at]  gmail.com

 Established in October 2014 at Gebze Technical University, Turkey

Biological Clock Lab Research

Nearly all organisms have circadian rhythms in their physiological functions. These circadian rhythms are generated by endogenous clocks, called circadian clocks, which provide a periodicity of about 24 hours even in the absence of environmental timing cues. A functional circadian clock consists of a “core clock” and a “photoreceptor system” which resets the core clock daily. In mammals, the core clock consists of an interlocked Transcription-Translation Feedback Loop (TTFL) with positive and negative arms. The positive arm induces transcription of negative arm components, which are then translated into repressors that inhibit the transactivation function of the positive arm. This activation/inhibition creates a cyclic expression pattern. However, post-translational modifications and secondary loops tune the circadian clock to approximately 24 hours . In TTFL, transcription factors Clock and Bmal1 induce the transcription of Cryptochrome (CRY) and period (PER) as well as many other circadian clock-regulated genes (CCG). In mammals, CRY and PER make a complex that translocates into the nucleus where they inhibit the Clock-Bmal1 transcriptional activity through direct protein-protein interactions Photoreception occurs in the eye of mammals where both classical photoreceptors (in rods and cones) and melanopsin (in a subset of retinal ganglion cells) receive the light signal and transmit it to the master circadian clock in the suprachiasmatic nucleus (SCN) in the brain. Downstream signalling causes acute induction of Per1 transcripts, which resets the circadian clock in the SCN. The SCN then resets the circadian clocks in peripheral organs by neuronal and humoral signals.

Circadian Clock in Mammals. Top Panel: Anatomical locations of Clocks. Clocks in peripheral tissues create the circadian oscillations of physiology. These peripheral clocks are synchronized by a master clock in the suprachiasmatic nucleus (SCN) by humoral and/or neuronal pathways. The endogenous master clock is slightly different from 24 hr. Light resets the master clock through the retinohypothalamic tract (RHT) daily therefore it is synchronized to the geological clock. Lower Panel: Circadian clock circuit. Clock-Bmal1 and CRY-PER form positive and negative arms of the Transcription Translation Feedback Loop, respectively. Clock-BMal1 activates the transcription of PER-CRY as well as circadian clock-regulated genes (CCG).  Accumulated CRY-PER enters the nucleus where it inhibits the Clock-BMal1 activity by protein-protein interaction. The circadian oscillation of CCG creates the circadian changes in physiology.