Postdoctoral Position Available

Vivian Budnik, Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Neurobiology

Other Affiliation(s):
   Interdisciplinary Graduate Program
   Program in Neuroscience

Molecular Mechanisms of Synapse Assembly and Plasticity

The major goal of the research in our lab is to understand the mechanisms by which synapses are formed and modified. In the nervous system, the elemental means of communication between cells is synaptic transmission. Essential to the high speed and efficiency by which neurons communicate is the exquisite molecular organization of the pre- and postsynaptic apparatus. At the presynaptic compartment, neurotransmitter-laden vesicles are poised at active zones, ready for immediate release, and the calcium channels necessary for triggering exocytosis are spatially linked to the secretory machinery. At the postsynaptic membrane, neurotransmitter receptors form high-density clusters which are directly apposed to the active zones. Thus, proper development and functioning of synaptic junctions requires positional information, which coordinates the correct placement of pre- and postsynaptic elements. Once synapses are formed, it is the ability of synaptic connections to strengthen or to weaken which is believed to be central to the processes of learning and memory, and the restoration of synaptic connectivity after a traumatic injury.

In the lab we are using a multidisciplinary approach that includes genetics, confocal and electron microscopy, electrophysiology and molecular biology to identify the proteins required to scaffold the synapse and to regulate it's molding during plasticity. Much of our studies are carried out using a Drosophila glutamatergic synapse model that has a high degree of evolutionary conservation with excitatory synapses in the mammalian brain. Using these approaches we have identified several proteins with fundamental roles in synapse formation and synapse dynamics, including Dlg, a member of the PSD-95 family, Wingless, a well-recognized factor for early embryonic pattern formation but with novel roles in synapse development, and APPL, the fly homolog of human APP, a protein with key roles in the development of Alzheimer's disease. This approach is proving to be extremely powerful in elucidating the cell biological mechanisms by which neuronal cell communication is established and modulated.

Representative Publications

Chai A, Withers J, Koh Y-H,  Parry K, Bao H, Zhang B, Budnik V,  and Pennetta G. (2007) hVAPB, the causative gene of a heterogeneous group of motor neuron diseases in humans, is functionally interchangeable with its Drosophila homologue DVAP-33A at the Neuromuscular Junction. Human Molec Genet (in press)

Li J, Ashley J, Budnik V and Bhat  MA (2007) Crucial Role of Drosophila Neurexin in Proper Active Zone Apposition to Postsynaptic Densities, Synaptic Growth and Synaptic Transmission. Neuron 55:741-755. Senior authors contributed equally to the work.

Speese, S. D., and Budnik, V. (2007). Wnts: up-and-coming at the synapse. Trends Neurosci 30, 268-275. 

Gorczyca, D., Ashley, J., Speese, S., Gherbesi, N., Thomas, U., Gundelfinger, E., Gramates, L. S., and Budnik, V. (2007). Postsynaptic membrane addition depends on the Discs-Large-interacting t-SNARE Gtaxin. J Neurosci 27, 1033-1044.

Ataman, B., Ashley, J., Gorczyca, D., Gorczyca, M., Mathew, D., Wichmann, C., Sigrist, S.J., and Budnik, V. (2006). Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP. Proc Natl Acad Sci U S A 103, 7841-7846.  

Mathew, D., Ataman, B., Chen, J., Zhang, Y., Cumberledge, S., and Budnik, V. (2005). Wingless signaling at synapses is through cleavage and nuclear import of receptor DFrizzled2. Science 310, 1344-1347.

Ashley, J., Packard, M., Ataman, B., and Budnik, V. (2005). Fasciclin II signals new synapse formation through amyloid precursor protein and the scaffolding protein dX11/Mint. J Neurosci 25, 5943-5955.

Ruiz-Canada C, Ashley J, Moeckel-Cole S, , Drier E, Yin J, and Budnik V. New Synapse Formation      Disrupted by Misregulation of icrotubule Stability in aPKC Mutants. Neuron 42, 567-80.

Mathew D, Popescu A, and Budnik V (2003) Drosophila Amphiphysin functions during synaptic Fasciclin II membrane cycling. J. Neurosci 23:10710-6

Packard M, Mathew D, and Budnik V (2003) FASt remodeling of synapses in Drosophila. Curr Op Neurobiol 13:527-34.

Packard M, Matthew D, and Budnik V (2003) Wnts and TGFb in synaptogenesis: old friends signalling at new places. Nat Rev Neurosci. 4:113-20

Packard M, Koo ES, Gorczyca M, Sharpe J, Cumberledge S, and Budnik V Budnik, V. (2002). The Drosophila wnt, wingless, provides an essential signal for pre- and postsynaptic differentiation. Cell 111: 319-330.

Roche J, Packard M, Moeckel-Cole S, and Budnik V (2002). Regulation of synaptic plasticity and synaptic vesicle dynamics by the PDZ protein Scribble. J. Neurosci. 22: 6471-6479.

Mathew D, Gramates LS, , Packard M, Gorczyca M, Bilder D, Perrimon N, and Budnik V (2002). GUK-holder, a Novel Synaptic Protein that Links the Tumor Suppressors Discs-large and Scribble. Current Biol. 12: 531-539.

Koh Y-H, Ruiz-Canada C, and Budnik V (2002). The Ras1-mitogen activated protein kinase signal transduction pathway regulates synaptic plasticity through fasciclin II-mediated cell adhesion J. Neurosci. 22: 2496-2504.

Koh Y-H, Popova E, Thomas U, Griffith L, and Budnik,V (1999). Regulation of DLG localization at synapses by CaMKII-Dependent Phosphorylation. Cell 98: 353-363.

Zhang B, Koh Y-H, Beckstead RB, Budnik V, Ganetzky B, and Bellen HJ (1998). Vesicle size and number are regulated by a novel synaptic protein required for endocytosis. Neuron 21: 1465-1475.

Thomas U, Kim E, Kuhlendahl S, Koh Y, Gundelfinger ED, Sheng M, Garner CC, and Budnik V (1997). Synaptic Clustering of the Cell Adhesion Molecule Fasciclin II by Discs Large and its Role in the Regulation of Presynaptic Structure. Neuron 19: 787-799.

Budnik V, Koh YH, Guan B, Haugh C, Woods D, and Gorczyca M (1996). Regulation of synapse structure and function by the Drosophila tumor suppressor gene, dlg. Neuron 17: 627-640.

Tejedor, F.J., Bokhari, O., Rogero, O., Gorczyca, M., Zhang, J., Kim, E., Sheng, M., and Budnik, V. (1996). Essential Role for dlg in Synaptic Clustering of Shaker K+ Channels in vivo. J. Neurosci. 17: 152-159.

Office: 703
Phone: 508-856-4341
E-mail: Vivian.Budnik@umassmed.edu

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Budnik for additional details.