This research will be done primarily in Argentina as an extension of NIH grant # RO1 MH51573. An organism's clock serves it as a temporal filter to time gene expression, cell metabolism, physiology and behavior to the most critical moments in the day, thus contributing to the organism's adaptation to a changing environment. Substantial progress has been made in elucidating the molecular process that imparts this temporal control. It is based in a transcriptional feedback loop, a widely conserved strategy for generating circadian oscillations; the ubiquity of this mechanism ensures that progress in one model will be of use to all. However, less information is available as to how the clock controls locomotor behavior. Gaining understanding in a model system like Drosophila most likely will impact the current thinking of how the clock controls sleep/activity cycles in mammals.
The aim of the present proposal is to investigate the role of a calcium-dependent voltage-gated potassium channel, slowpoke, in the consolidation of the activity cycles in the fruit fly.
The Specific Aims cover the analysis of mRNA and protein temporal profiles of slo and slob, two candidate genes putatively involved in circadian control of behavior; locomotor behavior analysis of strains carrying mutations in either gene under entrained and free running conditions; the molecular characterization of core oscillator function in a slo null (loss of function) mutant background and the analysis of the resetting response of the circadian pacemaker in a hypomorphic mutation (incomplete loss of function).
| Fernandez, Maria Paz; Berni, Jimena; Ceriani, Maria Fernanda (2008) Circadian remodeling of neuronal circuits involved in rhythmic behavior. PLoS Biol 6:e69 |
| Fernandez, Maria de la Paz; Chu, Jessie; Villella, Adriana et al. (2007) Impaired clock output by altered connectivity in the circadian network. Proc Natl Acad Sci U S A 104:5650-5 |
