Bio: Dr. Mark Ellisman is recognized for his leadership in developing new technologies that enhance biological research. He is the architect of an initiative known as the Biomedical Informatics Research Network (BIRN). The BIRN is a large scale program involving several NIH institutes intended to create test-beds to address the biomedical researchers' need to accumulate, access and analyze data at a variety of levels and sites across the country. This effort is complemented by a unique cross-disciplinary research program aimed at providing a new understanding of the molecular and cellular mechanisms of nervous system function.

He is actively involved in basic hypothesis-driven research grants, has the leadership role in two national programs for the NIH, building advanced imaging and information infrastructure. His academic standing is underscored by recent membership on the NIH/National Advisory Research Resources Council and the Physics Review Committee for Los Alamos National Laboratory.

Creative activities appear in Science, J of Neuroscience, Proceedings of the National Academy of Sciences, and Neuron. His research interests are broad in scope both from the bench perspective and the large scale instrumentation projects. The following are representative of major activities.

Investigations on the structure and function of the node of Ranvier and the molecular interactions between myelinating cells and axons in health and disease boast continuous long term NIH/NINDS support. Nodes of Ranvier are the sites along myelinated nerve where the nerve impulse is amplified and incrementally relayed along the nerve axons. Current work is based on the hypothesis that functions residing in specific subcomponents of the complex system regulate nodal physiological properties and therefore, play a critical role in governing subtle but important phenomena such as shifts in axonal conduction velocity.

For the past six years the Ellisman group has been actively engaged in developing a tagging system that could be used for both light and electron microscopy. In addition to demonstrating a powerful new technology, it showed how it could deliver information about the life cycle of proteins, when the new method is used in a 'pulse-chase' mode. The chemistry of this system derives from Roger Tsien and colleagues. In collaboration with his group, the system was refined within the test-bed problem of how gap junction plaques are formed by connexons. Dr. Ellisman had a longstanding idea to couple light and electron microscopy and to provide improved labels for 3D EM in order to facilitate mapping the substructure of the nervous system in the spatial domain between 1nm3 and 30um3. He also persisted with the notion that improved labeling was possible through the introduction of labels which could be marked for EM with photoconversion. Success came after about four years when the method was able to deliver results otherwise not obtainable by previous methods. Following publication in Science, the article 'Multi-color Electron Microscopic Imaging of Connexin Trafficking,' led to more than a dozen projects to disclose dynamics and locations of molecules in many systems, including pre and post-synaptic machinery. This is a unique and important technique that will be used by other investigators interested in molecular mapping in the nervous system.

The laboratory is also recognized for its defining work on a new view of astrocytes, the most abundant cell in the nervous system. They found that astrocytes are 85% more extensive than previously thought, and that their territories are unique and not overlapping. This is a very significant and fundamental change in our understanding of this cell type, and has substantial implications for the role of astrocytes in the nervous system. By injecting adjoining astrocytes in fixed tissue slices with different colored florescent dyes, it was possible to assess the distribution of the entire cell and determination of the relationships between neighboring cells. This work was published in the J of Neuroscience.

He also played a pivotal role in the development of a large scale program designed to access and analyze research data at a variety of levels at diverse sites across the country. The Biomedical Informatics Research Network (BIRN) was funded as a multi-institutional program in 2001. UCSD leads the program for NIH and Dr. Ellisman serves as Principal Investigator of the BIRN Coordinating Center. NIH expects that the BIRN will grow by a factor of at least two each year.

The large Ellisman laboratory provides a unique forum for teaching. He uses as many opportunities as possible to incorporate teaching. He routinely provides supervision for postdoctoral fellows as well as undergraduate students. Dr. Ellisman has placed special emphasis on minority undergraduate training and has been awarded an NIH research supplement for underrepresented minorities. The group has a tradition of involvement in educational outreach programs that include high-school students from the San Diego area and Washington, DC.

Dr. Ellisman has been singularly responsible for the establishment of a new campus Organized Research Unit (ORU) - The Center for Research in Biological Systems (CRBS) for which he continues to serve as Director. The CRBS is an umbrella organization for activities on campus relating to biological structure and function across spatial scales. During this period, the unit experienced substantial growth and formed a strategic alliance with the new California Institute for Telecommunications and Information Technology (Calit2).

Research:

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.