Cellular neurobiology and the dynamic interplay between structure and function in nervous system in general - with a focus on excitable membrane properties and new instrument design, development, and implementation.
Ellisman's well-established research activities include projects aimed at obtaining new insight into how the nervous system functions at the cellular level. Investigations are conducted on the cellular interactions occurring during nervous system regeneration, especially those occurring between axons and myelinating glia; structural changes in axons and synapses associated with changes in their functionally significant electrophysiological properties; aging in the central nervous system; cellular, molecular, and developmental neurobiology with specific interests in the mechanisms of intracellular transport in neurons; molecular differentiation of excitable membranes, ion channels, neurotransmitter receptors, and transmembrane ion pumps.
In addition to work in the domain science areas of basic cellular and molecular neurobiology, Ellisman's group is involved in the development of advanced confocal and high voltage electron-microscopic imaging methods as well as the associated computer-aided image processing and computer graphic display methodologies.
The following are excerpts from "An Interview with Mark Ellisman: Building an Imaging Collaboratory" Computers in Physics Vol. 10, No. 5, SEP/OCT 1996:
Although Mark Ellisman still looks upon the computer as a tool rather than an end in itself, he has become one of the parents of an ambitious project that aims to apply the resources of the Internet to create a molecular - and cellular - imaging collaboratory that will be open to researchers around the world. To develop the new, computer-intensive observational technologies requires a partnership between biologists, computer scientists and engineers, Ellisman says. "These tools don't often come from industry, they come - like most things in science - from the academic trenches through research and interdisciplinary activity," he says. "Then they often end up as products a few years later." The goal of Ellisman's own research is to understand how the nervous system works, by linking the function of nerve cells (neurons) to their macromolecular structure - particularly at synapses, the regions of close contact across which one neuron transmits signals to another. "There is a class of structural problems that fit into a size domain in between where the light microscope leaves off, about 0.25 micrometers, and where the electron microscope excels, around 1 nanaometer," he says. What is missing is a good description of structures in this size gap - structures that have small components but traverse large distances - such as synapses. "These components are not directly visible in the light microscope, and with traditional electron microscopy you see only parts of synapses," Ellisman says. "We're engaged in inventing microscopy and computer-aided analysis techniques that allow us to track supramolecular or interacting complexes in that dimensional gap," Ellisman says. "This should give us a three-dimensional understanding of how these synapses are structured, how the macromolecules that make them up relate to the functioning synapse," he says. Some of the techniques Ellisman uses involve light microscopy, but most involve three-dimensional electron microscopy. "We actually try to merge data sets from the two approaches," he says. "As you can imagine, we generate data sets that are quite large - on the order of a gigabyte - and that poses substantial demand for computational resources to explore them."
Prof. Ellisman is also the director of USCD's Center for Research in Biological Structure (CRBS). This new Center integrates the research and training activities of researchers in many departments at UCSD which involve biological structures from molecules to brains, ranging in dimensions from angstroms to centimeters. CRBS will include a significant component of computational neurobiology and is based at and linked to the San Diego Supercomputer Center, a national supercomputing facility located at UCSD.
Novakovic, S.D., Deerinck, T.J., Levinson, S.R., Shrager, P., and Ellisman, M.H. (1996), Clusters of axonal Na+ channels adjacent to remyelinating Schwann cells. J. Neurocytol. 25: 403-412.
YYoung, S.J., Fan, G.Y., Hessler, D., Lamont, S., Elvins, T.T., Hadida, M., Hanyzewski, G., Durkin, J.W., Hubbard, P., Kindalman, D., Wong, E., Greenberg, D., Karin, S., and Ellisman, M.H. (1996). Implementing a collaboratory for microscopic digital anatomy. Intl. J. Supercomputing Applic. and High Performance Computing, in press.
Fan, G.Y., Young, S.J., Deerinck, T., and Ellisman, M.H. (1996). New electron-optical mode for high contrast imaging and online stereo observation in TEM. J. Microsc. Soc. America, in press.
Martone, M.E., Pollock, J.A., Jones, Y.Z., and Ellisman, M.H. (1996). Ultrastructural localization of dendritic messenger RNA in adult rat hippocampus. J. Neurosci., in press.
Knowles, R.B., Sabry, J.H., Martone, M.E., Deerinck, T.J., Ellisman, M.H., Bassel, G.J., and Kosik, K.S. (1996). Translocation of RNA granules in living neurons. J. Neurosci., in press.
Martone, M.E., Alba, S.A., Airey, J.A., and Ellisman, M.H. (1997). Distribution of inositol 1,4,5 trisphosphate and ryanodine receptors in rat neostriatum. J. Comp. Neurol., in press.