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How animals keep time annually: molecular mechanisms of the seasonal rhythm

Wu Tsai Neurosciences Institute, Shixuan Liu, James Ferrell, Mark Krasnow

Adaptation to environmental variations is vital for animal survival. While short-lived organisms face unpredictable environmental fluctuations, long-lived animals are subject to regular and generally drastic environmental changes across different seasons. As an adaptation, many animals have evolved intrinsic seasonal rhythms, allowing them to anticipate and prepare for the changes in the environment. Examples include hibernation, migration, and fixed breeding seasons. Classical work suggests that, like the circadian rhythm, the seasonal rhythm is regulated by the photoperiods, but maintains to cycle even without external cues, implicating an internal seasonal clock. Photoperiod is sensed via inputs from the eyes, which integrate in the brain and translate into endocrine signaling (e.g., melatonin). However, it remains an untapped question what molecules and cells underlie the endogenous seasonal clock. I aim to tackle this poorly-understood question using an omics approach and a new animal model. Although seasonal rhythms are prevalent across the animal kingdom, the commonly used model animals like the mouse and rat are short-lived and show no distinctive seasonal rhythm. Other animals studied in the field typically lack the basic modern biology tools. In this study, I am introducing the mouse lemur, a mouse-sized primate that maintain robust seasonal rhythms (e.g., seasonal body weight changes, winter hibernation, and a fixed breeding season) throughout their 5-10-year lifespan in the lab. We have established useful genetics resources for the animal including an organism-wide cell atlas of the single-cell transcriptome. I am combining proteomic/metabolic profiling by mass spectrometry and transcriptomic profiling by single cell RNA sequencing to search for the molecules and cells that show seasonal patterns. This will open the door to understand the mysterious seasonal clock. By comparing with human data, it will shed light on seasonality of human physiology and may help inspire new treatment strategies for season-associated diseases and non-season-related metabolic syndromes.

Participants

Lead Researcher(s): 

Sponsor: James Ferrell (Chemical and Systems Biology) and Mark Kranow (Biochemistry)

Funding Type: 
Postdoctoral Fellowship
Round: 
6
Award Year: 
2020