Our lab studies brain development and function using a neurogenetic approach in Drosophila. Neurogenetics is the study of the genes that shape neuronal development and function. The genetic approach implies that it is indeed genes, their regulation and their products, that give rise to the complexity of neuronal networks. How can a few thousand genes and their regulatory elements contain the information required to, say, wire a fly’s brain to be capable of a feat like computing safe flight in three dimensions? We are interested in the mechanisms that lead to the synaptic specificity underlying such accurate and reproducible wiring of neuronal networks.
In addition to the molecular and cellular basis of brain wiring, we are interested in molecular mechanisms of synaptic function. Intracellular vesicle trafficking is known to have important instructive roles during both synaptic specification as well as function. Especially the molecular vesicle targeting and fusion machineries are critically required to regulate both the spatiotemporal regulation of various transmembrane receptors as well as neurotransmitter release. We are currently studying novel mutants in the vesicular ATPase as well as lipid-modifying enzymes that exhibit specific defects in membrane fusion. Our genetic approach is complemented with biochemistry, electrophysiology, live imaging and computational visualization techniques.
RESEARCH INTERESTS
Neurogenetics
Brain Wiring / Synaptic Specification
Synapse Function / Neurotransmitter Release
Membrane Fusion
Computational Approaches to 4D Visualization and Simulation
RECENT PUBLICATIONS
Hiesinger PR, Fayyazuddin A, Mehta SQ, Rosenmund T, Schulze KL, Zhai RG, Verstreken P, Cao Y, Zhou Y, Kunz J, Bellen HJ, "The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila." Cell, 121(4):607-20, May 2005
Hiesinger PR, Hassan BA, "Genetics in the age of systems biology." Cell, 123(7):1173-4, December 2005
Hiesinger PR*, Zhai RG*, Zhou Y, Koh TW, Mehta SQ, Schulze KL, Cao Y, Verstreken P, Clandinin TR, Fischbach KF, Meinertzhagen IA, Bellen HJ, "Activity-independent prespecification of synaptic partners in the visual map of Drosophila." Curr Biol, 16(18):1835-43, September 2006
Zhang, W., Wang, D., Volk, E., Bellen, H.J., Hiesinger, P.R.*, Quiocho, F.A.*, "v-ATPase V0 sector subunit a1 in neurons is a target of calmodulin" Journal of Biological Chemistry, 283:294-300, January 2008
Zhai, R.G., Zhang, F., Hiesinger, P.R., Cao, Y., Haeuter, C.M., and Bellen, H.J., "NAD Synthase NMNAT acts as a chaperone to protect against neurodegeneration" Nature, 452:887-91, April 2008
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