Project 5. Mathematical and experimental study on circadian phase-period relationship (Kwangwon Lee, Biology, Benedetto Piccoli, Mathematics)

Background. Most of the living organisms on earth are adapted to a 24 hr cycling environment due to the rotation of the earth. An organism’s ability to know the time of the day, and prepares the incoming stressful abiotic and biotic stresses, and also utilizes the expected changes of ambient environment is an important biological function for its survival in nature. The observable biological rhythm with about 24 hr period is collectively called circadian rhythm, and, the underlying molecular mechanism of circadian rhythm is called the circadian clock. When circadian clock is not working properly, it has been shown that the organism suffers adversary consequences, e.g. in humans, it causes diseases such as cancer, diabetes, and obesity. There has been great emphasis in characterizing the molecular mechanisms and mathematical modeling in 24 hr period oscillation of the clock in constant conditions. However, all pathological symptoms is the ‘phase’ phenotypes. The current dogma is that the ‘phase’ is the simple expression of the ‘period’ in cycling environment; a short period clock causes an advanced phase, and a long period clock causes a delayed phase. Thus, there has been attempt to explain pathological symptoms using the model that has been developed for ‘period’.

Research. We have analyzed the classical period mutants and measured their phase, and found that there is no linear relationship between period and phase. We also created backcross-mapping populations that share a homogeneous genetic background. The period and phase also reveals complex a relationship between these two phenotypes.

Student activities. Under the Dr. Piccoli’s supervision, a REU student will work on a mathematical model that describes the circadian rhythm and diurnal rhythms. The REU student will also perform experiments measuring period and phase of N. crassa under different environmental conditions In Dr. Lee’s lab. The experimental data will be used in optimizing the mathematical model. The outcome of the project will impact in our ability to understand the human clock disorders such as Familial advanced sleep phase syndrome.