X.Z. Shawn Xu Ph.D.
| Life Sciences Institute, 6115A |
| Ann Arbor, MI 48109 |
We are interested in understanding some of the fundamental questions in neuroscience: how sensory inputs are perceived by the nervous system, how neural circuits process information to generate behavior, and how genes and drugs of abuse regulate these processes. To address these questions, we use the genetic model organism C. elegans because of its simple and well characterized nervous system. We take a multidisciplinary approach combining molecular genetics, behavioral analysis, functional imaging, and electrophysiology.
Sensory transduction
The ability to sense and react to sensory stimuli is essential for life. Among the most common sensory stimuli are chemicals, mechanical forces and light. We are particularly interested in understanding how mechanical and light stimuli are detected and processed by the nervous system, and how genes regulate these processes. Specifically, we focus on proprioception (a special type of mechanosensation) and phototransduction. We have reported that proprioception, which is often referred to as the sixth sense, is present in C. elegans. Proprioception is important for controlling body posture, balance and movement, and represents one of the least understood sensory modalities. We have also reported a surprising observation that, despite the lack of eyes, worms sense light and engage in phototaxis behavior. These studies establish C. elegans as a powerful genetic model for studying the mechanisms of proprioception and phototransduction and their related diseases.
Neural circuits and genes that control behavior and drug addiction
How the nervous system and genes control behavior and drug addiction is a fundamental question in neurobiology. Despite extensive studies, it remains largely enigmatic as to how neural circuits process information to produce behavior, and how genes and drugs of abuse regulate this process. This largely results from the immense complexity of the nervous systems. C. elegans has recently emerged as an excellent model for approaching these questions because of its simple and very well characterized nervous system. We have recently developed novel tools to quantify behavior and record neural circuit activity, which would greatly facilitate mapping of neural circuits underlying behavior. We currently focus on the neural circuits that control sensory behaviors (e.g. phototaxis and proprioception) and drug dependent behaviors. To do so, we take a multidisciplinary approach combining molecular genetics, behavioral analysis, in vivo calcium imaging, and electrophysiology.
Xu, X.Z.S., Li, H.‑S., Guggino, W.B., and Montell, C. (1997). Coassembly of TRP and TRPL produces a distinct store‑operated conductance. Cell 89, 1155‑1164.
Wes P. D., Xu, X.Z.S., Li, H.-S., Chen, F., Doberstein, S. K., and Montell, C. (1999) Termination of phototransduction requires binding of the NINAC myosin III and the PDZ protein INAD. Nature Neuroscience 2, 447-453.
Li, H.-S., Xu, X.Z.S., and Montell C. (1999) Activation of a TRPC3-dependent cation current through the neurotrophin BDNF. Neuron 24, 261-273.
Xu, X.Z.S., Chien, F., Butler, A., Salkoff, L., and Montell, C. (2000) TRPg, a Drosophila TRP-related subunit, forms a regulated cation channel with TRPL. Neuron 26, 647-657.
Xu, X.Z.S., Moebius, F., Gill, D.L., and Montell, C. (2001) Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform. Proceedings of National Academy of Sciences U.S.A. 98, 10692-10697.
Xu, X.Z.S., and Sternberg, P.W. (2003) A C. elegans sperm TRP protein required for sperm-egg interactions during fertilization. Cell 114, 285-297.
Li, W., Feng, Z., Sternberg, P.W., and Xu, X.Z.S. (2006) A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue. Nature 440, 684-687.
Feng, Z., Li, W., Ward, A., Piggott, B.J., Larkspur, E., Sternberg, P.W., and Xu, X.Z.S. (2006) A C. elegans model of nicotine-dependent behavior: regulation by TRP-family channels. Cell 127, 621-633
Ward, A., Liu, J., Feng, Z., and Xu, X.Z.S. (2008) Light-sensitive neurons and channels mediate phototaxis in C. elegans. Nature Neuroscience (in press)
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