Research

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Neurogenetics

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? Our lab focusses on understanding the mechanisms that lead to the synaptic specificity underlying such accurate and reproducible wiring of neuronal networks.

Projects

Project Area 1: Synaptic Specificity / Brain Wiring

Pre-specification of synaptic partners in the visual map of Drosophila
Specifying synaptic partners and regulating synapse numbers are critical steps during visual map formation that are at least partly activity-dependent in all systems investigated to date. In contrast, in the Drosophila visual system each photoreceptor forms a precise and constant number of afferent synapses independently of both neuronal activity and synaptic partner accuracy. Our data suggest a cell-autonomous genetic program controlling synapse numbers as part of a developmental program of activity-independent steps that lead to a 'hard-wired' visual map in the fly brain. One major goal of our lab is to understand the molecular and cellular basis of these developmental and genetic programs.

REF: Hiesinger PR, Zhai RG et al., 2006, Current Biology 16, 1835-43.

Project Area 2: Synaptic Function / Vesicle Trafficking

Molecular mechanisms of membrane fusion in synaptic development and function
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.

REF: Hiesinger et al., 2005, Cell 121, 607-620.