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Dr. Murali K. Temburni |
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Research Interests |
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| We are interested in understanding the molecular mechanisms of brain development. Research in the Temburni lab is currently focused on two important phenomena that occur during neuronal development – synchronous activity and axon outgrowth. We use the chicken embryo, an excellent model system for vertebrate development to answer these questions, as it is amenable to surgical, cellular and molecular manipulations in ovo. The chicken genome sequence is complete and a GFP chicken is now available. Fundamental questions regarding early neuronal development and synapse formation can be addressed using the chick embryo. | ||
| 1. Role of astrocytes in the development of synchronous activity The first project, in collaboration with Dr. Melissa Harrington, Professor of Neuroscience, and Dr. Tomasz Smolinski, Associate Professor of Computational Neuroscience, at Delaware State University, is focused on unraveling the interactions between astrocytes, a type of glial cell, and neurons during the development of synchronous firing. Synchronous oscillatory activity in neuronal circuits plays a critical role in the establishment of functional networks in the developing nervous system although its mechanisms of formation are not fully understood. Existing models of synchronous activity assume that it is a process intrinsic to neurons. However, astrocytes have been shown to modulate synchronous activity in many brain areas – the cortex, hippocampus, thalamus and the nucleus accumbens. In the CNS glia outnumber neurons and recent evidence shows that glia not only guide synapse formation but also participate in synaptic transmission by releasing gliotransmitters like glutamate, ATP and D-serine. In addition, astrocytes communicate among themselves using intracellular Ca++ waves via gap junctions. The Tripartite Synapse, involving the presynaptic, postsynaptic neurons and the astrocyte proposed by Phil Haydon, is now a well-established concept. |
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| 2. APC - PSD93 interactions in neurite extension and axon determination This project is in collaboration with Dr. Michele Jacob, Professor of Neuroscience, Tufts University School of Medicine and Dr. Deni Galileo, Associate Professor of Neuroscience, University of Delaware. During development, progenitor stem cells give rise to neurons which migrate to different locations to form the embryonic brain. Once they reach their respective locations, neurons extend axons, which migrate great distances to reach their target neurons and begin synapse formation. The aim of this project is to understand the molecular mechanisms of axon outgrowth and synapse formation. Our specific goal is to dissect the role of the multifunctional protein Adenomatous Polyposis Coli (APC) and its binding partners in axon outgrowth. Our past research demonstrates APC’s important role in the formation of the post-synaptic structures. Preliminary results from our lab indicate that APC interacts with PSD93 protein to determine neuronal polarity and neurite outgrowth and with IQGAP1 to regulate axonal growth cone dynamics. We propose to elucidate the role of APC in these functions using a dominant negative (DN) strategy – by expressing small peptides designed to interfere with APC's interactions with specific binding partners, PSD93 and IQGAP1. Lentiviral vectors carrying cDNA sequences for the DN peptides will be used to infect chicken ciliary ganglion neurons growing in culture in vitro or injected into the neural tube of developing embryos in vivo. |
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| Techniques used In vitro cell culture and in ovo manipulations, expression of dominant negative constructs via lentiviral vectors, immunolocalization, epifluorescent and confocal imaging, time-lapse video microscopy and multi-electrode electrophysiology. |
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Summary of Center-Funded Research |
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