Research Overview
This overview encompasses major areas of research, core technologies, resources offered by NCMIR, and collaborative activities.
A key emphasis of the National Center for Microscopy and Imaging Research (NCMIR) is the application of advanced imaging technologies to the nervous system in health and disease.
Affiliated with UCSD’s Center for Research in Biological Systems (CRBS), the NCMIR is a recognized authority in the development of technologies for high throughput multi-scale imaging and analysis of biological systems at the mesoscale, the dimensional range spanning 5 nm3 and 50µm3. Macromolecules, organelles, and multi-component structures like synapses which are encompassed in this dimensional range have traditionally been challenging to study because they fall in the resolution gap between X-ray crystallography at one end and medical imaging at the other.
While maintaining a focus on neurobiology, NCMIR also conducts research that addresses the cellular and molecular underpinnings of biological systems relevant to cancer, diabetes, and heart disease, to name a few. NCMIR welcomes requests for collaborative projects that will drive development in its core research areas designed to develop and enhance technologies, including
- novel and traditional specimen preparation methods for intermediate voltage electron microscopy (IVEM) and correlated microscopies
- computer-aided methods for the acquisition of data from the microscopes
- enhancement of image contrast and extraction of accurate 3D information from biological specimens prepared for light and electron microscopy
- reconstruction of larger structural complexes using electron tomography and correlated microscopies
NCMIR also maintains a strong research program in computational biology and informatics through affiliated projects. As a leader in the development of informatics resources for microscopic imaging information, NCMIR makes the Cell Centered Database (CCDB) available to the scientific community. NCMIR plays a key role in the Biomedical Informatics Research Network (BIRN) initiative and is associated with the Center for Research in Biological Systems (CRBS) at UCSD. It is a significant domain driver of the California Institute of Telecommunications and Information Technology (Cal-IT2) and the San Diego Supercomputer Center (SDSC).
Core Technologies
NCMIR pursues a coordinated, three-pronged approach to achieving its goals of imaging biological systems on a grand scale, focusing core technology development in three areas:
- biological specimen development for intermediate voltage electron microscopes (IVEMs) and correlated microscopies
- instrumentation, including IVEM, camera development, and Telemicroscopy
- advanced software infrastructure applications and database development
These core technologies are detailed here.
NCMIR Offers
As a technology development center and P41 resource, NCMIR makes available for use intermediate voltage electron microscopes (IVEMs) and associated technologies for correlated microscopy, 3D reconstruction, and visualization, as well as advice and training in the application of these technologies. For a comprehensive listing of NCMIR resources available to outside users, refer to the Resources page. The facilities are open to visiting scientists and scientists in the Southern California area through collaborative, service, and training programs.
In addition to on-site technologies, NCMIR serves as a resource of resources, offering full remote access to rare and powerful high voltage electron microscopes including IVEMs and other unique high voltage electron microscopes around the world, such as the 3 MeV ultra high-voltage electron microscope at Osaka University in Japan, and the 1 MeV energy filtering JEOL high voltage electron microscope at the Korean Basic Sciences Institute in Seoul, Korea. NCMIR provides access to these instruments and an associated grid of richly integrated computational resources for performing electron tomography via the Internet through Telescience.
Researchers interested in using NCMIR technologies and facilities should complete the online User Application form.
For further information, contact the main office at (858) 534-0276.
Collaboration and Service
NCMIR delivers advanced capabilities to the biomedical research community through the interfacing of custom designed intermediate voltage electron microscopes (IVEMs) and light microscopes with advanced computational and graphics facilities. Technology development is driven by the needs of specific biological projects for specimen preparation, 3D investigations, and enhancement of microscopic imaging modes or computational tools. Biological projects are brought to NCMIR through an expanding collaborative and service research program.
NCMIR accepts requests for collaborative and service projects from outside users who require the advanced technologies NCMIR offers. Collaborative projects usually require significant involvement of NCMIR staff who will expand an already active area of technological research and development to accommodate new research endeavors. Service projects typically involve use of existing NCMIR facilities or technologies and do not require extensive resource staff involvement. For both types of projects, NCMIR provides the necessary training for visiting researchers to employ technology independently in their own laboratories. If a project requires significant staff resources, one or more NCMIR members are usually listed as co-authors on published works. For service projects, attribution of NCMIR’s contribution should be provided in the acknowledgements, but no authorship is expected.
Examples of collaborative projects driving technology development include
- examining neurogenesis in the adult hippocampus
- studying the trafficking of membrane proteins using correlated microscopies
- exploring in situ structure of supramolecular complexes using electron tomography
- creating computational models of synaptic structure based on tomographic reconstructions
- redefining mitochondrial structure in health and disease
- investigating spine morphologies in an animal model of mental retardation
- uncovering synaptic alterations resulting from an episode of transient ischemia
For additional information on accessing NCMIR technologies, see the User Application form.
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