Intellectual merit. Circadian clocks are important coordinators of physiological and behavioral rhythms. Drosophila melanogaster serves as an excellent model for investigating clock mechanisms, however little is known about the functional significance of clock genes in the fly physiology. The group led by Dr. Giebultowicz demonstrated that peripheral circadian clocks play multiple roles in reproductive physiology. Recent research revealed that two essential clock genes, period and timeless, are involved in the regulation of female fecundity. Surprisingly, these genes seem to act not as components of the circadian clock but as part of a homeostatic mechanism. An integrated physiological and molecular approach is proposed to investigate this novel fitness-related phenotype. Preliminary data led to a hypothesis that proteins encoded by period and timeless are part of the signaling pathway that modulates the rate of egg production. This hypothesis will be tested in an experimental program divided into four objectives. (1) Several aspects of reproductive physiology will be compared between mutant and wild-type females, to determine if mutant females have altered endocrine functions or other physiological parameters that may account for their failure to increase oogenesis in response to protein-rich diet. (2) A genetic approach will be used to determine whether increased fecundity of flies on high-protein diet is dependent on the function of period and timeless genes in the ovary, or in other organs such as the nervous system. (3) Expression of period and timeless will be investigated at the mRNA and protein level to determine whether it is affected by female age and nutritional status. (4) Biochemical tools will be used to elucidate the role of period and timeless in female fecundity. Accomplishment of these objectives will be aided by the wealth of genetic information and the ease of molecular manipulations in Drosophila, which make it an ideal system for the dissection of multi-component nutrient-fecundity pathway. The results of these studies will help to understand the functional significance of phylogenetically conserved clock genes in a genetic pathway regulating fecundity. Broader impact. Scientific program outlined here will facilitate partnerships between several faculty members, graduate, and undergraduate students. The proposed research will provide ample opportunities for training students; participants from groups underrepresented in science will be actively recruited to the program. The combination of physiological, molecular and genetic experiments will allow students to gain experience in the interdisciplinary approach to research. Students will be mentored with respect to their academic goals and encouraged to consider career in science. Dr. Giebultowicz has an excellent record of engaging undergraduate female students in her research and helping them to choose science as a career. The PI also integrate research activities into the teaching of science in area schools. She is a co-PI in the NSF-funded K-12 Rural Science Education Program at OSU, mentoring undergraduate and graduate students who help to teach science in selected rural schools in Oregon. She also participate in "Adventures in Learning" program for middle school girls, inviting students to the lab to conduct small experiment, offering hands-on approach to science. Research results obtained with NSF funds will be published in peer-reviewed journals, and research highlights will be posted on the laboratory web-site in a format accessible to the general public.
