This program project grant revolves around the development and function of the nervous system. The two experimental organisms, Drosophila and C. elegans, underscore an additional common theme of the application: the molecular basis of neural function and behavior in genetic systems. The links between the five projects/laboratories are therefore practical as well as intellectual. In the first and second project, the Drosophila circadian clock will be investigated. There is arguably more known about the molecular basis of circadian rhythms in Drosophila than in any other eukaryotic organism. Yet there are only two identified Drosophila clock components (PER and TIM), and neural substrate features of this system are primitive. The first Project proposes to identify biochemically additional clock components, and the second Project will largely focus on neural and physiological issues that address the Drosophila pacemaker mechanism. The third Project will focus on two Drosophila genes, elav and appl. ELAV provides a vital function essential for proper formation of the nervous system, and it has recently been shown that it functions as a regulator of neuron-specific alternate splicing. The application proposes to investigate with biochemical and genetic procedures how ELAV regulates splicing, with significant input from the Rosbash laboratory. Proposed experiments on APPL will test the hypothesis that it acts as a receptor that influences neuronal arbors and synapses. The fourth Project proposes to continue and extend studies on the contribution of CaM kinase to plastic behaviors, including learning and memory.
Specific aims i ncludes the identification of neurons requiring CaM kinase, the characterization of CaM kinase- dependent biochemical pathways, and characterization of the larval neuromuscular junction phenotype of animals with alterations in these biochemical pathway. Significant input for the Hall lab on courtship conditioning as well as from White lab on tyrosine beta hydroxylase mutant is anticipated. The fifth Project proposes to study olfaction in C. elegans. Specifically, the focus is on the regulatory gene odr-7 and its role in the determination of the AWA subtype of olfactory neurons and its sensory properties. Odr-7 encodes a unique member of the nuclear receptor family of transcription factors.
Specific aims i nclude the identification and characterization of targets of odr-7 regulation, analysis of the effects of spatial and temporal control of odr-7 expression, and the identification of additional genes required for the determination of sensory specificity of the AWA neurons.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG2 (01))
Program Officer
Tompkins, Laurie
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brandeis University
Schools of Arts and Sciences
United States
Zip Code
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

Showing the most recent 10 out of 79 publications