This Program Project grant revolves around the development and function of the nervous system in Drosophila. Many of the approaches involve genetics and molecular biology. In Project I (Rosbash) and II (Hall), circadian rhythms will be investigated. Several such studies will apply existing """"""""clock"""""""" mutations and cloned DNA defined by mutant alleles at a locus called period (per). In addition (Project I), it is proposed to isolate several new circadian rhythm mutants, using chemical and transposon-mobilization mutageneses. It is also proposed to initiate molecular analyses of certain emerging rhythm mutants. In Project II, the neural substrates of Drosophila's circadian rhythms will be delved into. Cyclings of per product levels, known to fluctuate with circadian periodicities, will be dissected molecularly, immunohistochemically, and behaviorally. Searches for interspecific relatives of the per gene will be made. In project III (White), the influence of two genes on Drosophila's embryonic development will be analyzed. One is embryonic-lethal/abnormal-visual-system (elav), whose encoded. protein will be studied with regard to its presumed role in the control of neuronal-specific mRNA processing. Putative targets of ELAV's action will be looked for in genetic and biochemically based screens. Aberrant expression of elav will be analyzed, by molecularly characterizing conditional mutants, and eliciting ectopic expression of the gene's product(s). The other gene, erect-wing (ewg), which is expressed in the nuclei of developing neurons and muscle precursors, will be investigated with regard to possible involvement in transcriptional regulation. Project IV (Lisman) involves the function of Drosophila photoreceptors. The two reactions involved in the first stage of transducing visual stimuli [activation of G-protein by light-activated rhodopsin (M*), and the reaction by which M* is deactivated] will be quantitated. Molecular manipulations of a cloned opsin gene-- to eliminate most of the putative phosphorylation sites-- will be effected in order to: measure the rate of M * deactivation and gain and determine if the reliability of this deactivation is impinged upon. A separate photoreceptor-based subproject will connect with Projects I and II, whose previous studies showed that per expression is prominent in these visual-system cells. Project V (Griffith) will study the role of the multifunctional calcium/calmodulin protein kinase II (CaM kinase) and its relatives in experience-dependent behavior. Gene cloning, biochemical characterization, spatial expression studies, and the identification of other biochemical components that contribute to behavioral plasticity are the goals of this project.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
2P01GM033205-09
Application #
3096211
Study Section
Special Emphasis Panel (SSS (R))
Project Start
1984-07-01
Project End
1997-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Brandeis University
Department
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Vodala, Sadanand; Pescatore, Stefan; Rodriguez, Joseph et al. (2012) The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs. Cell Metab 16:601-12
Shang, Yuhua; Haynes, Paula; Pírez, Nicolás et al. (2011) Imaging analysis of clock neurons reveals light buffers the wake-promoting effect of dopamine. Nat Neurosci 14:889-95
Hall, Jeffrey C (2005) Systems approaches to biological rhythms in Drosophila. Methods Enzymol 393:61-185
Choi, James C; Park, Demian; Griffith, Leslie C (2004) Electrophysiological and morphological characterization of identified motor neurons in the Drosophila third instar larva central nervous system. J Neurophysiol 91:2353-65
Busza, Ania; Emery-Le, Myai; Rosbash, Michael et al. (2004) Roles of the two Drosophila CRYPTOCHROME structural domains in circadian photoreception. Science 304:1503-6
Park, Demian; Coleman, Melissa J; Hodge, James J L et al. (2002) Regulation of neuronal excitability in Drosophila by constitutively active CaMKII. J Neurobiol 52:24-42
McDonald, M J; Rosbash, M; Emery, P (2001) Wild-type circadian rhythmicity is dependent on closely spaced E boxes in the Drosophila timeless promoter. Mol Cell Biol 21:1207-17
Joiner, M A; Griffith, L C (2000) Visual input regulates circuit configuration in courtship conditioning of Drosophila melanogaster. Learn Mem 7:32-42
Joiner, M A; Griffith, L C (1999) Mapping of the anatomical circuit of CaM kinase-dependent courtship conditioning in Drosophila. Learn Mem 6:177-92
DeSimone, S; Coelho, C; Roy, S et al. (1996) ERECT WING, the Drosophila member of a family of DNA binding proteins is required in imaginal myoblasts for flight muscle development. Development 122:31-9

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