Joshua M. Kaplan

Department of Genetics
Massachusetts General Hospital
Department of Molecular Biology
Richard B. Simches Research Building
185 Cambridge St., CPZN-7250
Boston, MA 02114
Tel: (617) 726-5900
Fax: (617) 726-5959
Email: kaplan@molbio.mgh.harvard.edu
Web Page: The Kaplan Lab Page
6 postdoctoral fellows, 5 graduate students, 6 completed Ph.D.s

Work in my lab is focused on understanding how signals in the brain lead to particular patterns of behavior. We utilize a combination of behavioral, genetic, biochemical, imaging, and electrophysiological techniques to study signaling in the brain of the worm C. elegans.

Presynaptic mechanisms. To identify new presynaptic components, and potential G proteins targets, we conducted two systematic RNAi screens. In one screen, we looked for genes that whose inactivation decreased muscle activity, identifying 132 new proteins required for synapse structure and function. In a second screen, we looked for genes whose inactivation increases muscle activity, identifying 93 genes. The function of these genes is being analyzed in more detail. In particular, we have shown that many of these genes alter muscle activity by disturbing the balance between synaptic excitation (at cholinergic NMJs) and inhibition (at GABAergic NMJs). Characterizing these genes will provide new insights into how the excitation-inhibition balance is set.

Regulation of insulin and neuropeptide secretion. Insulin secretion, and its misregulation, plays a pivotal role in aging, diabetes, and obesity. We have developed assays for insulin secretion in intact worms. Using these assays, we have begun characterizing mechanisms regulating insulin secretion, and genetic screens to identify new genes that regulate insulin secretion. Current projects aim to identify factors that differentially regulate secretion of classical neurotransmitters versus secretion of neuropeptides (e.g. insulin).

Synapse formation and trafficking of synaptic proteins. We have developed methods for visualizing individual synapses in living worms. Using these methods, we identified several genes that regulate synapse formation, and targeting of receptors to synapses. Current projects aim to define how these proteins regulate synapse formation.

References:

• Sieburth, D., Q. Ch’ng, M. Dybbs, M. Tavazoie, S. Kennedy, D. Wang, D. Dupuy, J.F. Rual, D.E. Hill, M. Vidal, G. Ruvkun, and J.M. Kaplan. (2005) Systematic analysis of genes required for synapse structure and function. Nature, 436(77050): 510-7.
• Dittman, J. S. and J.M. Kaplan. (2006) Factors regulating the abundance and localization of synaptobrevin in the plasma membrane. Proc Natl Acad Sci U S A, 103(30): 11399-404.
• McEwen, J.M., J.M. Madison, M. Dybbs, and J.M. Kaplan. (2006) Antagonistic Regulation of Synaptic Vesicle Priming by Tomosyn and UNC-13. Neuron, 51(3): 303-15.
• Sieburth, D., J.M. Madison, and J.M. Kaplan. (2007) PKC-1 regulates secretion of neuropeptides. Nat Neurosci, 10(1): 49-57.