Destabilization of the PAS domain core in the Earlydoors mutation of mouse Period2 accelerates the circadian clock
Physical and Biological Sciences
Chem 195ABC
This thesis focuses on the molecular mechanisms of circadian rhythms in mammals, which are responsible for the sleep and wake cycles that we all experience. Outside of sleep, many other physiological processes are regulated – such as hair growth, bowel movements, immune responses, metabolism, and even the expression of some genes – by these intrinsic rhythms. My research project involved an investigation into how the periods of these cyclic pathways are determined. In collaboration with two groups at the University of Oxford and Cambridge, I studied how a mutant version of the clock protein Period2 (PER2), significantly decreases the circadian period in mice. My data show that the mutation, named Earlydoors, caused the structure of PER2 to be less stable than its normal counterpart, leading to more rapid loss of the protein and a shortened circadian period. These findings inform us about the relationship between the structure of PER2 and its function as a regulator of circadian timekeeping.
