Current Students | Andrew Rosselot
URC Graduate Summer Fellow
Health Sciences Graduate Student Association — representative to the Committee on Graduate Education
The body operates on a schedule of approximately 24 hours, a response to entrainment by light/dark cycles. This schedule is our circadian (circa = about, diem = day) rhythm and is a cornerstone in the field of chronobiology. Circadian rhythms are controlled by specific clock genes – BMAL1, CLOCK, PER and CRY – that work in a transcriptional translational feedback loop. The focus of the Hong lab is to understand how these clock genes regulate the cell cycle and other physiology by utilizing both mammalian and fungal models using benchtop and mathematical modeling techniques. This allows us to understand the differences in physiology at different time points during the day. An example of time-of-day variation in physiology and disease is seen in the differential colonization of Salmonella based on what time a mouse is infected (see Bellet, 2013 PNAS). This highlights the need for experimental designs that take into consideration time-of-day variation and also alludes to the potential for improved efficacy of drugs that are directed to be taken at specific times.
Publications, Complete List at PubMed
My project works to understand possible changes in robustness of the clock due to aging. Commonly, elderly individuals sleep less than younger people do and also have inconsistent energy levels. Lack of sleep or altered circadian rhythms is starting to be investigated as a potential component in diseases such as diabetes, Crohn's disease, colitis, and irritable bowel syndrome. An example of this is the high incidence of gastrointestinal ailments in jet-lagged individuals. I am investigating the endogenous clock of the small intestine using the robust 3D enteroid in vitro model derived from human and mouse small intestinal stem cells. This model allows us to visualize the rhythmic expression of relevant circadian genes using bioluminescent reporters and can be readily perturbed to understand what factors may be altering our clock. My main goal is to investigate how aging might be resulting in a natural decline in rhythmic function of the endogenous clock within the intestine and also to provide potential mechanisms that may be leading to the phenotype.