The overall goal of this proposal is to understand how a circadian clock (or pacemaker) accommodates new phase alignments in response to seasonal changes in ambient temperature and daylength (photoperiod), a topic that has received little attention from a molecular perspective. This feature of circadian clocks has immense biological significance because it enables organisms to (1) adopt optimal phase-alignments between physiological and behavioral rhythms and the prevailing environmental conditions, and (2) trigger seasonally appropriate responses. A major foundation for the proposed specific aims in this application is based on our recent published work [Majercak et al., (1999) Neuron, 24:219] showing that the thermosensitive splicing of the 3-terminal intron from the D. melanogaster period (dper) RNA (herein refereed to as dmpi8; D. melanogaster dper intron 8) makes a major contribution to the preferential daytime activity of this species during seasonally cold days. Recent findings indicate that whereas the splicing efficiency of dmpi8 is stimulated by cold temperatures, light inhibits this splicing event, demonstrating intricate multi-modal regulation. Our findings suggest that the thermal and photoperiodic regulation of dmpi8 splicing acts as a """"""""seasonal sensor"""""""" conveying calendar information to the animal. In this application we propose to determine how temperature and light co-regulate the splicing efficiency of dmpi8. No only will these studies investigate a novel effect of light on the D. melanogaster circadian clock but our recent findings implicate a new role for the visual signal transduction cascade in the phase control of activity rhythms driven from deep brain pacemaker cells. Moreover, we will analyze the clockworks and behavioral rhythms in several Drosophila species from a wide range of latitudinal gradients. These studies might reveal a role for natural selection in the adaptation of circadian clocks to geographical variations in seasonal climates. To accomplish these goals we propose to take multifacted experimental strategies including in vitro biochemical, tissue culture and whole animal approaches. With the recent realization that the basic molecular logic underlying circadian clocks from a wide variety of organisms, including humans, is conserved, it is anticipated that although specific details will differ our investigation of how a circadian clock integrates multiple environmental modalities will lead to general principles that are applicable to a wide range of circadian systems.
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