Gina E. Sosinsky, Ph.D., Assistant Director

Gina E. Sosinsky, Ph.D. is a Professor-In-Residence in the UCSD Department of Neurosciences and Assistant Director for NCMIR.

Dr. Sosinsky is dedicated to exploring the molecular structure of gap junctions and other structures of cell-cell junctions. These studies are being conducted using high-resolution electron microscopy (EM). Gap junctions are one of the primary ways that cells communicate with each other. They are specialized cell contact areas that contain hundreds to thousands of channels. These channels allow for the passage of molecules from one cell’s cytoplasm to another, thereby providing a fast and efficient means of signaling and cooperation. They are found in almost all tissues in which cells abut each other. Connexin26 (Cx26) is the smallest of the gap junction protein family and is also one of the most functionally important. It is found in significant quantities in many major organ systems including brain, liver and intestine and human mutations are the leading cause of hereditary deafness worldwide.

The Sosinsky laboratory has isolated Cx26 gap junctions as in situ ordered two-dimensional crystals for analysis by electron microscopy (EM) structure determination, atomic force microscope imaging (AFM) and biochemical studies. The focus is on structure and functional dynamics of Cx26 gap junction channels. Using high resolution AFM, the group has been able to visualize conformational changes at submolecular resolution (10 Å laterally, 2Å vertically).

In a closely related line of study, Dr. Sosinsky is looking at the cellular organization of gap junctions and identifying structural intermediates in connexin trafficking by specific labeling and electron tomography. Gap junctions are unique in that the channels are rapidly being assembled and degraded by multiple mechanisms; not all of the channels within the same junctional plaque are active at the same time. Research efforts are aimed at understanding how the connexin organizes into and functions within the gap structure and how the connexins organize and interact with other cellular components. The primary tool used is the electron microscope that provides excellent resolution to determine the molecular structure of gap junction proteins as well as their arrangements within and between cells. Multiple microscopies such as confocal and atomic force microscopy in addition to electron microscopy are used to better understand gap junction dynamics.

Her group did ground breaking work on pannexins, a similar protein to connexins. However, her group showed that these channel proteins are glycosylated, do not form gap junctions and serve a different function in inflammation and apoptosis.  Dr. Sosinsky and her group have investigated the expression of these proteins are in the central nervous system and in collaboration, with a group at Harvard Medical School, have shown that pannexin1 plays a role in the activation of the cardiac inflammasome after myocardial infarction. 

Dr. Sosinsky’s group is able to chronicle protein dynamics in living systems followed by direct visualization of individual macromolecules in situ in the same preparation, with minimal need for tissue treatments that negatively impact ultrastructure. Using this approach, the Sosinsky laboratory was able for the first time to unequivocally determine that new gap junction proteins are added to the periphery and removed from the central region of plaques in cells. This work was described in a paper published in Science in 2002. Another recent publication in the journal Traffic in 2010 highlighted that recycling of connexin hemichannels occurs during mitosis.

In complementary studies, Dr. Sosinsky continues to explore the nodes of Ranvier and their relationship to gap junction structure. Nodes of Ranvier are sites on myelinated axons where the insulating layers of myelin are interrupted. Myelinated axons and their nodes of Ranvier represent an important evolutionary advance for vertebrates that permit very rapid propagation of action potentials without large increases in axonal diameter. Studies are aimed at examining the possible mechanisms of interaction between axons and myelinating glia to understand more about how the nodal complex manages and modulates propagation of the nerve impulse.

The Sosinsky and Ellisman groups hypothesize that functions residing in specific subcomponents of this extremely 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. They are specifically involved in gathering and extracting new information about the structural organization of the node using molecular labeling and electron tomographic imaging. The group uses novel methods of selective staining and tomography for obtaining accurate and high resolution information about the three dimensional structure in situ (down to the macromolecular scale) using intermediate high voltage electron tomography. The combined results will significantly increase our understanding of saltutory conduction and contribute to the development of new strategies for treatment of disorders involving myelinated axons.

Dr. Sosinsky serves as Principal Investigator and is lead organizer for the Interfaces in Biology course on Microscopy Techniques. She is part of the Interfaces in Biology Graduate Specialization Program (http://interfaces.ucsd.edu), a cross-department, interdisciplinary program originally funded by HHMI and now NIBIB and UCSD to provide practical lab training to graduate students at the interfaces between the biological, health, physical and engineering sciences. Dr. Sosinsky is PI for the experimental tomography efforts (including molecular labeling techniques and experimental data collection) within the P41 National Center for Microscopy and Imaging Research Resource. She was the project originator of the Electron Microscopy Outreach Program. This was a joint project between the National Center for Microscopy and Imaging (NCMIR) and the San Diego Supercomputer Center (NPACI/SDSC).

Outside professional activities include serving as Assistant Editor for the Journal of Biological Chemistry, Editor for Microscopy Research and Technique. She has served twice as a guest editor for Cell Communication and Adhesion. She has been an ad hoc reviewer for such premier publications as the Journal of Neuroscience, Science Signaling, PNAS, Biochemical Journal and Biophysical Journal. She is head of the 3DEM mailing list and web site, a resource for the field of molecular and cellular 3D structure. There are over 1500 subscribers worldwide to this list. Additionally, she has been a frequent grant reviewer for NIH and NSF.

Dr. Sosinsky has been very active in the Microscopy Society of America. She is on Council for MSA as a Biological Director. Other notable activities include her participation in the organization of several conferences key among which was her role as Chair for several Three Dimensional Electron Microscopy at the Gordon Conferences. She has presented a number of invited lectures at the national level. She was Co-Chair of the Women in Science and Engineering Committee and continues her membership on that committee.

View Dr. Sosinsky's curriculum vitae.

Assistant Director, National Center for Microscopy and Imaging Research (NCMIR)
Professor-In-Residence, University of California, San Diego
University of California, San Diego (UCSD)
9500 Gilman Drive,
La Jolla, CA 92093-0608