Courtship
(Hall and Griffith)Circadian Rhythms (Rosbash and Hall)
The Hall and Rosbash labs have a long-term collaboration aimed at understanding biological rhythms. Molecular and behavioral studies of circadian rhythms in Drosophila have provided insight into the workings of internal clocks of both flies and mammals. Early work on the per gene began the modern era of circadian rhythm studies. This included the identification of a Drosophila transcriptional feedback loop, now known to be central to the clocks of plants, cyanobacteria, Neurospora, and mammals. More recent genetics has expanded the clock gene world to include five new Drosophila clock genes, the last three of which were identified at Brandeis: timeless (tim), doubletime (dbt), Clock (Clk), cycle (cyc), and cryptochrome (cry). All six known fly clock genes have orthologues known or suspected to be important for circadian timekeeping in mammals.
Biochemical, anatomical and genetic approaches are utilized not only to identify and understand clock components but also to uncover components of the input and output pathways. These studies have identified a few key central nervous system cells that contain input and output molecules as well as the central pacemaker. This in vivo neurobiological focus will allow a more detailed understanding of the connections between the circadian pacemaker and biological processes within the living animal.
Courtship
(Hall and Griffith)
Reproductive behavior is robust. A number of aspects of these behaviors are stereotypical and therefore easily quantified, but significant plasticity exists to allow the animals to adapt to novel situations. Drosophila provides a genetically tractable system in which to investigate the molecular basis of behavior.
The Hall lab uses behavioral and genetic approaches to understand how the sexual identity of the nervous system and its output is specified. The fruitless gene (fru), a complex locus, is involved in sex determination. Other mutants such as dissonance (diss) and cacophony (cac), which were isolated due to courtship song abnormalities, are involved in a number of other behaviors.
Courtship learning, the ability of a male fly to modify its behavior after exposure to a mate female, is being used by the Griffith lab to dissect the biochemical events underlying memory formation. The roles of ion channels and calcium/calmodulin-dependent protein kinase II are being investigated using both mutants and dominant transgenic strategies. Anatomical circuits responsible for courtship plasticity have been defined using cell-specific expression of these transgenes.
Development of the Nervous System (White)
The construction of a working nervous system involves the concerted action of many genes. The White lab studies four of these genes: Appl (ß amyloid protein precursor like), elav (embryonic lethal, abnormal visual system), vnd (ventral nervous system condensation defective) and ewg (erect wing). Biogenic amines and their functional roles in the nervous system are also studied.
EWG and VND are transcription factors that function in embryos for early specification of nervous system development. ELAV is an RNA-binding protein that is capable of regulating neural-specific alternative splicing of several target genes including ewg, arm and nrg. The Appl gene is thought to function late in neural development in synapse formation and maintenance. Deletion mutants are viable but have behavioral abnormalities. Study of this collection of genes is
Motor Proteins (Welte)
The Welte lab studies how cells regulate microtubule motors. Such motors play crucial roles in many cellular processes, but although much has been learned about how single motors function in vitro, the problem how cells deploy them in a controlled manner remains unsolved: What controls the timing of their activity? What determines cargo specificity? How do multiple motors cooperate with each other? To address these questions, the Welte laboratory examines the transport of lipid droplets in Drosophila embryos. This model system allows both direct visualization of transport by videomicroscopy and identification of molecules mediating transport by genetic analysis.
Lipid droplets employ a sophisticated bi-directional transport machinery whose activity is developmentally regulated. This machinery utilizes Klarsicht, which also functions in nuclear migration during eye development, and cytoplasmic dynein, a motor important for the transport of many cargoes. To dissect the machinery further, the laboratory will employ genetic screens to identify mutations in other components and regulators, with the goal of characterizing them molecularly. These genetic and molecular tools will make it possible to address two general issues: 1) What are the molecular changes that bring about the changes in motor activity during development? 2) Other cargoes use at least in part the same machinery, but are regulated differently. Which components are cargo-specific, and are they responsible for the differential motor behavior?
Synaptic Plasticity (Griffith)
The regulation of neuronal activity is central to learning and memory. Calcium-dependent signal transduction has been shown to be involved in plasticity in many model systems. The Griffith lab is interested in the biochemical events that are triggered during plastic change in adult brain and at the larval neuromuscular junction. Behavioral, genetic and electrophysiological approaches are used to understand the role of calcium/calmodulin-dependent protein kinase II in synaptic plasticity
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