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UNIVERSITY OF MASSACHUSETTS

Abstract: Paradigm shifting studies in the monarch butterfly (Danaus plexippus) have enhanced our view of the evolution and function of circadian clocks in animals. The Specific Aims of Parent Grant expand our knowledge of the unique properties of the CRYPTOCHROME (CRY) proteins by defining distinct CRY mechanisms of action in the circadian clocks of lepidopterans (butterflies and moths) using molecular, biochemical, genetic, and behavioral approaches. Because of the parallel, complementary nature of circadian clock discoveries between flies and mammals, which can now be extended to lepidopterans, our overriding hypothesis is that further analysis of the two families of animal CRY proteins that are represented in insects will advance our fundamental understanding of animal clock mechanisms. The Specific Aim of the Competitive Revision is to generate a high depth sequence of the monarch butterfly genome using a combination of state-of-the-art 'next generation' sequencing technologies, and then appropriately assemble, annotate and interpret the genome. To fully develop the monarch butterfly as a model organism to study circadian clock mechanisms and the associated molecular mechanisms of sun compass navigation used during migration, a sequenced and fully annotated genome is needed. This resource would greatly advance each Aim of the Parent Grant and would be of value to the larger neuroscience/genomics/evolutionary biology research communities. A major goal is to define the molecular mechanisms of the animal clockwork. Sequencing and annotating the monarch butterfly genome will greatly enhance our ability to increase our fundamental understanding of clockwork function from an evolutionary perspective and demonstrate the monarch butterfly as a useful model in which to study animal clock mechanisms. Likewise, such understanding should lead to new strategies for pharmacological manipulation of the human clock to improve the treatment of jet lag and shift-work ailments, and of clock-related sleep and psychiatric disorders. PUBLIC HEALTH RELEVANCE: Understanding the molecular clock should increase our knowledge of how clock gene mutations contribute to psychopathology and some sleep disorders. Likewise, such understanding should lead to new strategies for pharmacological manipulation of the human clock to improve the treatment of jet lag and shift-work ailments, and of clock-related sleep and psychiatric disorders.

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