Our group is interested in the larger questions of how our brains adapt and what happens when neurons in the brain die or perform abnormally. The remarkable adaptability of brains of all animals, including, of course, humans, relies heavily on the lifelong ability of individual neurons to change in response to specific stimuli. It is this so called neuronal plasticity that forms the research focus of our laboratory. The favored model organism for our studies is Drosophila, or the fruit fly (more correctly, the Pomace Fly), which, though surprising to some, shows a remarkable range of “learning behavior” as it navigates through life. What makes this a truly advantageous model organism, however, is the vast array of genetic tools at the disposal of the experimental biologist and the ability to assay plasticity at multiple levels of complexity. In principle one could understand how a gene of interest controls a certain behavior, neuronal circuits that operate this behavior, the physiology of an individual identified neuron and finally, cellular events inside this neuron. Our current interests fall into four sub-categories:

	A. Transcriptional networks regulation pre-synaptic plasticity: We typically assay pre-synaptic plasticity by measuring synaptic size and strength at the neuromuscular junctions of Drosophila larvae. This glutamatergic synapse undergoes activity dependent growth using cellular mechanisms involved in long-term plasticity in mammalian systems. Using this preparation we are testing unique roles for a handful of “interesting” transcription factors (such as the IE transcription factor, AP1 and the better studied CREB). Ongoing research aims to uncover both signaling cascades that impinge on these transcription factors as well as identify their downstream targets.
	B. Understanding the plasticity of neuronal dendrites in vivo: Though it has been the focus of intense research, few experimental preparations exist that assay dendritic plasticity in vivo. We have used genetic strategies to label individual motor neurons in the larval CNS, and followed this up with confocal imaging, 3D reconstruction and statistical measurements to ask how dendrite growth and branching is influenced by neural activity, signaling cascades and the activity of relevant transcription factors.
	C. The role of the p38 MAP Kinase in neuronal function and degeneration: Unlike ERK and JNK, p38 Kinases are relatively less understood in the context of the nervous system. In significant part, this arises due to the presence of multiple p38K genes and isoforms in mammals. Consistent with a streamlined genome, flies have two p38K genes. In our efforts to understand its function in the nervous system, we have knocked out both genes and are currently investigating consequences on lifespan, stress tolerance, motor behavior, synaptic plasticity as well as synergistic effects with known genetic determinants of longevity and neurodegeneration in flies.
	D. Genetic models of Restless Legs Syndrome in flies: A recent, and rather ambitious, endeavor in the laboratory is an attempt to generate genetic models of the Human condition called Restless Legs Syndrome (RLS). Following suggestions from large scale linkage studies that a gene, BTBD9 is perhaps intricately linked with the incidence of this disorder, we are currently trying to uncover physiological functions for a highly conserved homolog in flies. Do flies have restless legs? We do not know yet, but it will not be too surprising if they do!