Understanding diapause and its ability to suspend and preserve life Project Summary/ Abstract “Suspended animation” may seem like a term only appears in science fiction, but it does exist in several forms in nature. Many organisms have evolved unique states of dormancy to survive unfavorable conditions. Frequently, these dormant states demonstrate extraordinary abilities for physiological features not seen during the active states of life. However, while life comprises both active and dormant states, our research has been mainly focused on the former, such as development, growth, proliferation, and aging. As a consequence, our knowledge of how organisms live in dormancy remains limited. Studying dormancy is thus crucial not only for filling in the gap in knowledge to complete our understanding of life, but also for exploring how to best leverage this knowledge to improve the quality of life during our active states. My vision is to accelerate our understanding of dormancy and its functional implication by studying the dormant state of diapause with a newly established research organism - the naturally short-lived African killifish (Nothobranchius furzeri). My research subject in diapause and my research system in the African killifish consist of two novel components for this proposal. Among various forms of dormancy, diapause at the embryonic stage is especially intriguing. Diapause evolved a rare capability to suspend embryonic development for months or even years without compromising subsequent development and adulthood physiology. The natural characteristics of a long diapause coupled with a short lifespan in the African killifish present a uniquely suited platform to feasibly experiment the functional implication of diapause in vertebrates. Diapause in the African killifish thus holds the key to a fascinating new field focusing on mechanisms of the suspension and preservation of life. In this proposal, I will first focus on the signaling mechanism of diapause, then expand to the interplay between diapause and development and/or aging. Lastly, I will explore the mechanisms underlying translating diapause to active life. By leveraging the new technologies of genome editing, single-cell biology, time-lapse microscopy, coupled with my established resources and tools, I expect to fulfill my research vision by 1) obtaining a thorough knowledge of the signaling pathways in diapause, and 2) building an experimental platform to elucidate the functional implication of diapause. Together, the knowledge and the platform complement each other and compose a powerful system conceptually and experimentally to help us understand diapause and its functional implication to life.

Understanding diapause and its ability to suspend and preserve life Project Narrative As a natural form of “suspended animation”, diapause is a dormant state which can suspend embryonic development and preserve life for an extended time without compromising following health and life. However, our knowledge of how diapause works, especially in a more complex vertebrate system, remains limited. Here we study diapause through two complementary angles – signaling pathways and functioning mechanisms – using a naturally short-lived African killifish for its remarkable ability for staying in diapause to survive the drought for up to years.