Mission Statement:

 

The mission of NCMIR is to develop technologies to bridge understanding of biological systems between the gross anatomical and molecular scales and to make these technologies broadly available to biomedical researchers. NCMIR provides expertise, infrastructure, technological development, and an environment in which new information about the 3D ultrastructure of tissues, cells, and macromolecular complexes may be accurately and easily obtained and analyzed. Read More >>

 

Research Highlights

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High-performance serial block-face SEM of non-conductive biological samples enabled by focal gas injection-based charge compensation

In collaboration with Carl Zeiss Microscopy (www.zeiss.com), NCMIR researchers developed a new technology for improving the performance of serial blockface scanning EM (SBEM) using the Gatan 3View. This technology allows for the focused and synchronized delivery of nitrogen gas to the sample blockface during the imaging cycle to eliminate charging, greatly extending the utility of the volume imaging technique for even the most-charge-prone samples.

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Intrinsic Assembly of Neural Circuits

Scientists at The Scripps Research Institute (TSRI) and the National Center for Microscopy and Imaging Research (NCMIR) in La Jolla have revealed new clues to the wiring of the brain.  A team led by Associate Professor Anton Maximov, in collaboration with Dr. Mark Ellisman’s group, have found that neurons in brain regions that store memory can form networks in the absence of synaptic activity.

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Brain Synapse Size Grows Larger, Then Smaller in Regular Cycle Between Wakefulness and Sleep

A team of researchers at the University of Wisconsin-Madison and UCSD/NCMIR  discovers that synapses in mouse cerebral cortex strengthen (grow larger) during wake to support learning but decline in strength (grow smaller) during sleep to consolidate memories and restore cellular function.

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Multicolor Electron Microscopy Used to Visualize Multiple Molecular Components Inside a Cell

This method applied different lanthanides to label specific cellular components. The lanthanides’ electron energy-loss spectra were visualized, and the resulting elemental maps overlaid on a conventional greyscale EM image to “color-code” the labeled components and enable tracking of their movements over time across multiple images.

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NCMIR Develops New Technique to Improve Resolution of SBEM Images

Applying a negative voltage to an SBEM stage creates a reversal potential that decreases the landing energy of probe-beam electrons. At a lower landing energy, probe electrons penetrate more shallowly, resulting in improved resolution. The reversal potential further accelerates backscattered electrons, leading to a large increase in their recorded signal by the detector.    

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Using Click-EM for Metabolic Labeling to Track and Image Tagged Non-protein Biomolecules by Light and Electron Microscopy

UCSD and NCMIR researchers introduce a powerful new approach for metabolic labeling and imaging of non-proteinaceous cellular components by light and electron microscopy.

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Advances in Molecular Labeling Tools Enhance Results Using Multiscale, Multimodal, Correlated Microscopies

Scientists at the National Center for Microscopy and Imaging Research (NCMIR) have summarized four recently developed, now widely used, electron microscopy (EM) probes (also called labels or tags) in a review to facilitate more general adoption of new probes and methods from the center.

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CNS Myelin Turnover Mechanism Clarified: Astrocytes Eliminate Cellular Debris Resulting from Removal of Myelin Segments as the Optic Nerve Shortens During Frog Metamorphosis

Researchers at The Johns Hopkins University School of Medicine, the Hugo W. Moser Research Institute at Kennedy Krieger, Inc., and the National Center for Microscopy and Imaging Research demonstrated that, in a developing vertebrate ON, individual myelin segments can shorten in response to shortening in axon length, revealing a plasticity of myelin segments not previously known. Through volume EM-based quantification, the team further demonstrated that axon myelin segments shorten through selective astrocytic phagocytosis of small intra-segmental myelin dystrophies.

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Remodeling of the Nuclear Pore Complex by the p75 Neurotrophin Receptor Controls Transforming Growth Factor Signaling and Astrocyte Functions

Researchers from UC San Francisco, the University of Freiburg (Germany), UC San Diego and its National Center for Microscopy and Imaging Research, the University of Glasgow (UK), King’s College London, and Stanford University team to establish a potential, previously unknown, mechanism by which the brain responds to injury.

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New Insight Toward Understanding the Molecular Basis for Long-term Memory

Human memory can persist for a lifetime, yet the majority of synaptic proteins in the brain turn over at a rate of hours to days. Synthesizing, localizing, and stabilizing new protein copies at synapses are crucial factors in maintaining the synaptic changes required for storing long-term memories.  To gain insight into how long-lasting changes in synaptic strength are sustained, a research team from UC San Diego and the Howard Hughes Medical Institute investigated PKMζ and PKCλ stability in rat neurons.

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New Experimental Protocols for Correlative Stochastic Optical Reconstruction Microscopy and EM

A research team from the Howard Hughes Medical Institute, Harvard University, the National Center for Microscopy and Imaging Research, and UC San Diego developed a new method that combines 3D stochastic optical reconstruction microscopy (STORM) with several EM imaging modes, including protocols to image unembedded and embedded/sectioned samples. They applied the resulting protocols to several cellular and viral structures.

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APEX2 Enhances Proximity Labeling and Electron Microscopy Imaging to Resolve Dispute about Regulation of the Inner Membrane Channel

A research team from MIT, Massachusetts General Hospital, and UCSD in late November 2014 published a study in Nature Methods describing an electron microscopy tag, APEX2, which they developed for live-cell proteomics and genetic probe-based labeling for light and electron microscopy. Use of this tag enabled them to resolve a conflict between competing mechanistic models of regulation of the inner membrane channel through which calcium is supplied to mitochondria.

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Automatic Segmentation of Organelles in Electron Microscopy Image Stacks: A New Workflow

Electron microscopy is a very useful technique to analyze the form, distribution, and functional status of key organelle systems in various pathological processes including those associated with neurodegenerative diseases. Significantly, it has been used to provide important new insights into the mechanisms underlying diseases such as Parkinson’s and Alzheimer’s diseases and glaucoma.Moreover, recent advances in EM instrumentation are fueling a renaissance in the study of quantitative neuroanatomy. Data obtained from techniques such as serial block-face scanning electron microscopy (SBEM) provide unprecedented volumetric snapshots of the in-situ biological organization of the mammalian brain across a multitude of scales.

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X-ray Microscopy Increases Accuracy and Efficiency of SBEM Imaging for Correlated Light/Electron Microscopy of Biological Specimens

The recently developed 3D method of serial block-face scanning electron microscopy is rapidly establishing itself as a powerful imaging approach in the biological sciences research community. This approach is proving of great value for 3D visualization of nervous system ultrastructure, particularly when details of synaptic and other subcellular elements must be located and quantified. It is also important for constructing connectomic models of regional brain circuits. In addition, SBEM is increasingly used to perform nanohistology on a wide variety of tissue systems, including the lung, liver, tendons, kidney, and cell cultures.

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Epik! A New Scientific Workflow for Electron Tomography

Computational researchers, regardless of their disciplines, need software tools that save time, optimize and scale up computations, produce results faster, create an extensible platform, foster collaborations, effectively communicate the underlying science, and enable others to replicate the results. Some of the most effective tools are based on scientific workflows. A workflow is a software application that solves a scientific problem. It’s composed of computational steps and data manipulation tools that can scale up to run on high-performance computers, distributed environments, and commercial cloud systems. Workflows are used in all stages of the data lifecycle: generation and acquisition, analysis, comparison, publication, and archiving.

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PRIME Directive: New Chemical Fluorophore Designed to Tag Cell Proteins for Imaging

Fluorescent proteins are used commonly to tag components of interest in living cells for subsequent imaging. But there’s a cost: Their dim fluorescence, rapid photobleaching, and large size limit their utility, and they can disrupt protein folding and trafficking and/or impair protein function.Chemical fluorophores, by comparison, tend to be considerably smaller, brighter, and more photostable, characteristics that allow them to perform better in advanced biological imaging modalities such as single-molecule tracking and super-resolution microscopies. However, it is much more challenging to target them to specific cellular proteins inside living cells because they cannot be genetically encoded and have to target proteins post-translationally inside a complex cellular environment.

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Astrocytes Devour Neuronal Mitochondria in a Newly Documented Process Called Transmitophagy

Scientific canon long held that when the tiny energy producers within cells, called mitochondria, become damaged or dysfunctional, these tiny organelles are degraded and recycled within the cell that produced them. But a paper appearing in the Proceedings of the National Academy of Sciences (PNAS) from The Johns Hopkins University and NCMIR scientists now shows that, instead, particularly in the long axons of the brain’s nerve cells, damaged mitochondria are transferred to nearby glial cells for elimination. This process, in effect, outsources a substantial portion of the neurons’ housekeeping. Read More > >
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A New Model System for Neural Development Produces Nanoscale-resolution Animations that Inspires Music

Neural circuit development in mice is characterized by early exuberant innervation followed by competition and pruning to mature innervation topography. Several neural systems (e.g., the neuromuscular junction ad climbing fiber innervation of Purkinje cells) have served as models to study neural development in part because they establish a recognizable endpoint of mono-innervation of their targets, and the presynaptic terminals are large and easily monitored. The calyx of Held (CH) innervation of its target, which forms a key element of auditory brainstem binaural circuitry, exhibits these same characteristic. Read More > >
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De-coating Caveolae: Understanding the Caveolar Protein Machinery in Endocytosis

Caveolae are flask-shaped invaginations with a diameter of 50-80nm in the plasma membrane of many types of mammalian cells. They are particularly abundant in fat cells, muscle cells, and cells that line blood vessels and serve as a source for clathrin-dependent endocytosis. Although they are likely to be important for cellular responses to mechanical stress, intracellular trafficking, and signaling events, the precise molecular mechanisms that determine how they form and carry out these functions have yet to be understood. Read More > >
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Three Types of Microscopy Go To the Limit to Determine Ryanodine Receptor Calcium Release Channels in Cardiac Myocytes

A research team led by UCSD recently published results of their work using various kinds of microscopy to reveal the relative distribution of ryanodine receptors and caveolin-3 in mouse ventricular myocytes in the cytosol and near the cell surface. Ryandine Receptors are important to investigate because they comprise a class of intracellular calcium channels that mediate the release of calcium in various types of mammalian tissue like muscles and neurons. Read More > >
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Liprin-α1/SYD-2 Determines Size of Electron-dense Projections in Presynaptic Active Zones in C. elegans

Fast synaptic neurotransmission relies on triggered release of neurotransmitters from synaptic vesicles after fusion with the plasma membrane. The release of synaptic vesicles is a highly regulated process of sequential events: First synaptic vesicles are recruited to the presynaptic active zone, then docked to the plasma membrane in a release-competent state, which guarantees their rapid release after the influx of calcium into the presynaptic terminal. Read More > >
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Big Data Analysis: Applying Electron Microscopy to Semi-automated Neuron Boundary Detection and Non-branching Process Segmentation

Reconstructing neural circuits is important to studying neural circuit connectivity and its behavioral implications. Understanding the differences between neuronal classes, patterns, and connections is critical to enable a more general understanding of how neural circuits process information. Electron microscopy is a useful method to determine the anatomy of individual neurons and their connectivity because it has a resolution that is high enough to identify features such as synaptic contacts and gap junctions, which define connectivity and, therefore, are required to reconstruct the neural circuit. But because the complexity and size – often approaching tens of terabytes -- of this data make for very difficult and labor-intensive interpretation, new segmentation techniques for identifying neurons in these data sets are needed. Read More > >
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Efficient, Scalable, and Cost-effective 3D Microscopy Image Segmentation Using a Microlabor Workforce

In an applications note published in Bioinformatics, a team of researchers from the National Center for Microscopy and Imaging Research at UCSD described a new scalable, semi-automated approach to segment 3D structures revealed in serial block-face scanning electron microscopy (SBEM) images. The team used the Dual Point Decision Process (DP2) to divide the segmentation problem into discrete tasks distributed to a large pool of individual workers. Read More > >
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Adenovirus Protein may be a Key to Strategic New Cancer Therapies

A team of scientists led by Clodagh O’Shea’s group at The Salk In100stitute for Biological Studies in collaboration with NCMIR scientists (Mark Ellisman, Tom Deerinck, Andrew Noske) and Dr. Roger Tsien and his laboratory suggest that cold viruses could serve as a valuable tool in the fight against cancer. Adenovirus, a type of cold virus, has developed proteins that allow it to hijack a cell's molecular machinery particularly those involved in growth, replication and cancer suppression. Read More > >
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Origins of Aggressive Brain Tumors

Scientists have long believed that glioblastoma multiforme (GBM), the most aggressive type of primary brain tumor, begins in glial cells that make up supportive tissue in the brain or in neural stem cells. In a paper published in Science, researchers at the Salk Institute for Biological Studies and the National Center for Microscopy and Imaging Research have found Read More > >
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Ocean Bacteria Infected by Strange Looking Viruses

NCMIR researchers aided in the discovery of the most abundant virus in the ocean. This virus, called a Pelagiphage, attacks the most abundant microorganism in our oceans, a type of marine bacteria called SAR11, with significant implications for how carbon moves between the atmosphere and our oceans. SAR11, a bacterium that's the most abundant organism in the oceans, survives where most other cells would die and plays a major role in the planet's carbon cycle. It had been theorized that SAR11 was so small and widespread that it must be invulnerable to attack. Pelagiphages are so strange-looking that scientists previously didn't even recognize what they were. Read More > >
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Accumulated Excess Protein Linked To Development Of Parkinson’s Disease By Progressively Disrupting Neuronal Function And Viability

NCMIR scientists have shown that overexpression of a protein called alpha-synuclein appears to disrupt vital recycling processes in neurons, starting with the terminal extensions of neurons and working its way back to the cells’ center, with the potential consequence of progressive degeneration and eventual cell death. Published in the February 6, 2013 issue of The Journal of Neuroscience, this study has major implications for more fully understanding the causes and mechanisms of Parkinson’s disease (PD), a neurodegenerative movement disorder that affects an estimated 1 million Americans. Read More > >
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Electron Microscopy Achieves A New APEX

Chemists from MIT together with NCMIR Scientists, Mark Ellisman, Tom Deerinck and Gina Sosinsky, have now designed a GFP equivalent for electron microscopy — a tag that allows scientists to label and visualize proteins with unprecedented clarity that offers much higher resolution than fluorescence microscopy. The new tag developed by Jeff Martell and Alice Ting, lead and senior authors of a paper describing the new tag in the Oct. 21 online edition of Nature Biotechnology, could help scientists pinpoint the locations of many cell proteins, providing new insight into those proteins’ functions. This new tag can label proteins throughout the cell — not only within mitochondria but also in the nucleus, the endoplasmic reticulum and the cytosol. Read More > >
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It's Not What You Eat But When You Eat

Researchers at the Salk Institute led by Dr. Satchidananda Panda with NCMIR collaborators, published a provocative paper In the June issue of Cell Metabolism showing that mice fed a high calorie/high fat diet on a time restricted feeding schedule were protected against obesity and related complications compared to mice eating the same amount of calories ad libitum. Read More > >
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New Insights into the Role of LRRK2 Mutations in the Pathogenesis of Parkinson's Disease

Mutations in the leucine-rich repeat kinase 2 (LRRK2) are associated with increased risk of developing Parkinson’s disease. Kett and colleagues, in collaboration with researchers at NCMIR, have uncovered a novel association of mutant LRRK2 with microtubules using advanced labeling and microscopy techniques. In cultured neurons, LRRK2 mutations appear to enhanced LRRK2 oligomerization, causing it to form filamentous structures visible by light microscopy. Read More > >
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Correlative Microscopy Webinar

n April 4, 2012, Mark Ellisman, NCMIR Director, participated in a webinar on “Correlative Microscopy” sponsored by the Biophysical Society, the Biophysical Journal and Cell Press. Moderated by Dr. Paul Wiseman, Associate Professor of Physics and Chemistry at McGill University, the topics in this webinar ranged from combining light, electron microscopy (both selectively stained thick section EM tomography or cryo-EM tomography) and soft X-ray tomography. Read More > >
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NCMIR Researchers Help Create a Powerful New Probe for Light and Electron Microscopy

In the April 5th issue of PLoS Biology, NCMIR scientists, in a collaboration with a team led by Nobel laureate Roger Tsien, introduced a new fluorescent probe for correlated light and electron microscopy that overcomes many of the limitations previously encountered by researchers seeking to image cells and tissues at high resolution. Read More > >
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UC San Diego's National Center for Microscopy and Imaging Research (NCMIR) Instrumental in Huntington's Disease Breakthrough

Imagine being able to prevent certain death of nerve cells in the brain and visualizing the feat with the latest in electron microscope technology. That's just what a team of biomedical researchers did, including UC San Diego's own National Center for Microscopy and Imaging Research (NCMIR), giving hope to Huntington's disease patients. Huntington’s disease is an inherited and incurable neurodegenerative disorder affecting 35,000 people annually and is caused by mutation of the gene encoding the huntingtin protein. Read More > >
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New Research Reveals Unexpected Biological Pathway In Glaucoma

In a study published in the Proceedings of the National Academy of Sciences, a team of researchers from the Kennedy Krieger Institute and four collaborating institutions, including the National Center for Microscopy and Imaging Research, identified a new and unexpected biological pathway that appears to contribute to the development of glaucoma and its resulting vision loss. Read More > >
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Serial Block-Face Scanning Electron Microscopy at the 2010 Microscopy and Microanalysis Meeting

At the 2010 Microscopy and Microanalysis meeting in Portland, Oregon, NCMIR scientists presented their work "Enhancing Serial Block-Face Scanning Electron Microscopy to Enable High Resolution 3-D Nanohistology of Cells and Tissues," a collaboration with researchers Roger Tsien's laboratory at UCSD.

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NCMIR Scientists Provide the First Glimpse of Synthetic Life

Pioneering geneticist J. Craig Venter and colleagues announced the creation of the first synthetic life form, Mycoplasma mycoides JCVI-syn1.0 at a press conference in Washington, D.C. and NCMIR researchers were entrusted with obtaining the first images of this new organism. Read More > >
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Sestrin Protects Fruit Flies From Age-Related Pathologies NCMIR Image Featured on Cover of Science

NCMIR scientists were members of a team of researchers that studied the intricate link of TOR with sestrins, a family of highly conserved proteins whose expression is induced by stress. Read More > >
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NCMIR’s Electron Tomography Resource Reveals Novel Mitochondrial Anchoring Scaffolds and Cristae Structured for High-rate Metabolism

Electron microscope tomography was used at the NCMIR to aid Prof. George Spirou (West Virginia University) in his investigation of the mitochondria-associated adherens complex (MAC) in the auditory brain stem and resulted in a publication in the J. Neuroscience. Read More > >
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Direct Restriction of Virus Release and Incorporation of the Interferon-Induced Protein BST-2 into HIV-1 Particles

In their paper, "Direct Restriction of Virus Release and Incorporation of the Interferon-Induced Protein BST-2 into HIV-1 Particles" published in PloS Pathogens, NMCIR researchers, in collaboration with Kathleen Fitzpatrick and John Guatelli of the UCSD School of Medicine show that the cellular protein BST-2 is involved in retaining newly formed HIV-1 virions on the surface of cells. Read More > >
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Mitochondrial configurations in peripheral nerve suggest differential ATP production.

NCMIR researchers used electron tomography to examine mitochondria, the cell’s principal energy producers, in the peripheral nervous system (PNS) in a study that points to differential energy usage along neurons. The morphological diversity of mitochondria in neurons appears to be the rule rather than the exception as these cells are highly polar, being composed of dendrites, somas, synapses, and axons — compartments with differing functions, molecules, and energetic needs. Read More > >
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New insights into mitochondrial structure during cell death

In this research effort, NCMIR neuroscientists and investigators at the Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, examined the pivotal role mitochondria play in the cascade of events associated with cell death pathways involved with several forms of neurodegeneration. Read More > >
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Three-dimensional electron microscopy reveals new details of membrane systems for Ca2+ signaling in the heart.

Using electron tomography, the NCMIR investigators in this study mapped the 3D topologies of dyadic clefts and associated membrane organelles in the mouse ventricular myocardium. Morphological details and the distribution of membrane systems, including transverse tubules (T-tubules), junctional sarcoplasmic reticulum (SR) and vicinal mitochondria, involved in controlling cardiac Ca2+ dynamics, were determined. Read More > >
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NCMIR scientists in combination with Salk Institute is the first to model axonal conduction to include a more realistic three-dimensional geometry of cellular microdomains.

Electrochemical signal transduction in cells depends on the subcellular organization of structural components, as well as on the electric profiles created by electrodiffusion of ions. Electrochemical diffusion is particularly important in nerve impulse transduction. With respect to neuronal cells and even at a higher systems level such as brain tissue, a fundamental question arises: how can seemingly similar cells such as neurons have such different electrophysiological properties from one another? Read More > >
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NCMIR collaborators demonstrate the use of fluorescent quantum dots for tracking dendritic cells and priming an immune response in vitro and in vivo.

Dendritic cells play a key role in initiating adaptive immune response by presenting antigen to T cells in lymphoid organs. NCMIR collaborators Michael Cahalan, Debasish Sen and Ian Parker at the University of California Irvine along with NCMIR scientists Thomas Deerinck and Mark Ellisman investigated the potential of using quantum dots as fluorescent nanoparticles for in vitro and in vivo imaging of dendritic cells, and as a particle-based antigen-delivery system to enhance denditic cell-mediated immune responses. Read More > >
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The CCDB Releases a New Version of Web Site to Make Sharing Microscopy Data Easier: http://ccdb.ucsd.edu

Originally deployed in March 2002 under the auspices of NIH’s Human Brain Project, the Cell Centered Database (CCDB) accommodates the storage and manipulation of high-resolution 3D light and electron microscopic reconstructions and facilitates advanced electron tomography.
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NCMIR collaborators reveal how new neurons, born in the hippocampus, wire into the brain’s circuitry

Just over a decade ago the idea that the mammalian brain contains stem cells that divide and differentiate into new neurons continually throughout life was largely unimaginable. However, with the recent body of research showing that areas of the adult brain continually undergo neurogenesis, neuroscientists have adopted a new paradigm in thinking about the brain. Read More > >
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UCSD Researchers Reveal Dynamic Behavior of Golgi Complex

Researchers at UC San Diego reveal new details about the life cycle of the Golgi apparatus—the organelle responsible for correctly sorting, targeting, and trafficking protein in our cells. Constructing a novel protein tag suitable for light microscopy and correlated high-resolution electron microscopy, the team overcame intrinsic problems in observing the Golgi while undergoing cell division.
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NCMIR researchers help biologists reveal greater structural detail.

In step with its mission of advancing the analysis of 3D structures in neurobiology and cell biology, a team of NCMIR researchers is helping biologists to take advantage of large-field electron microscope imaging developments for improving the resolution of 3D structures at the scale of proteins.
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4th International Congress on Electron Tomography (4ICET)

NCMIR organized and hosted the Fourth International Congress on Electron Tomography (ICET) in San Diego on November 5-8, 2006. Convened three times since 1997, this conference provides a forum for structural and cell biologists, materials and computational scientists, and others to exchange information about how electron tomography (ET) elucidates structure-function in cellular arrays and larger assemblies. Read More > >
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NCMIR's Telescience is featured in Science Grid This Week

The Telescience™ Project started over a decade ago as an effort to make rare scientific instruments globally accessible. Researchers at the National Center for Microscopy and Imaging Research began developing technologies to remotely control bio-imaging instruments over the Internet, and in 1992 the first system was demonstrated when attendees at a conference in Chicago interactively acquired and viewed images from one of NCMIR's intermediate voltage electron microscopes in San Diego. Read More > >
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NCMIR’s electron tomography reveals ultrastructural details about how a phytoplankton adapts to changes in light intensity

Tiffany Moisan of NASA’s Goddard Space Flight Center at Wallops Island Virgina teamed up with NCMIR researchers to investigate the morphological changes associated with a marine alga, Phaeocystis antarctica, grown in light-limiting and high light environments. Their study, reported in the journal Marine Biology, presents the first 3D structures determined by electron tomography of an ecologically important phytoplankton species. Read More > >
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Studies of mouse models of human disease helped by NCMIR’s large-scale imaging expertise

Scientists studying the nervous system have long struggled to understand how higher order structures, such as cellular networks, are assembled out of finer building blocks, such as dendritic and axonal architectures. Mapping the entire neural structure is the key to elucidating brain function. In a forthcoming issue of Neuroinformatics, a team of NCMIR researchers report on their progress towards this central goal by describing new procedures to study brain architecture and to characterize pathological changes in transgenic mice, spanning millimeter- to nanometer-sized structures. Read More > >
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NCMIR researcher wins second and eighth place in the Nikon International Small World Competition.

Nikon Corp has announced the winners of the 2005 Nikon International Small World Competition. Local NCMIR scientist Tom Deerinck garnered a second and an eighth place in the prestigious competition with his images of tissues stained with fluorescent quantum dots. According to Nikon: “The Nikon Small World competition recognizes the fusion of science and art as captured through the lens of the optical microscope. Read More > >
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Quantum Dots allow NCMIR scientists image cellular and subcellular detail from a single preparation.

Cell biologists at UCSD’s National Center for Microscopy and Imaging Research (NCMIR) demonstrate the suitability of Quantum dots (QDs) for determining the specific location of endogenous proteins in cells and tissues—using correlated light and electron imaging techniques. Read More > >
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NCMIR and Salk Researchers “animate” synaptic transmission

In a collaboration between computational neuroscientists and neuroanatomists, researchers have created a 3-D, nano-scale “anatomically correct” neuronal synapse that provides new insights into the way synapses work. Efforts to model activities of the nervous system have generally required drastically simplifying the complex geometry of the brain and its microscopic components. Read More > >
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3D Mouse Model Reveals Complex Structures of the Node of Ranvier

NCMIR researchers, in collaboration with the Salk Institute, have created a 3D model of the node of Ranvier, a complex structure found in the nervous system of higher vertebrates. The results will be published in an upcoming issue of Neuroinformatics. Read More > >
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Tomography Method Improves Resolution in Thick Samples

A novel method for acquiring data for electron tomography dramatically increases resolution and usable section thickness of stained samples, according to a NCMIR study published in the December 2004 issue of the Journal of Structural Biology. Read More > >
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Astrocytes Limit CNS Regeneration

Investigators at Göteborg University and the University of Southern California found astrocytes play a significant role in limiting the regenerative capacity of the central nervous system. In the May 26, 2004 issue of the Journal of Neuroscience, researchers collaborating with NCMIR’s Eric Bushong demonstrated reactive astrocytes lacking intermediate filaments in mice show a limited hypertrophy of cell processes and synaptic regeneration in the hippocampus. Read More > >
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BioWall Displays Large Images of the Brain

NCMIR's newly installed "BioWall" tiled display, a 20-tile wall of high-resolution flat-panel displays that project massive, detailed 2D and 3D images of the brain, allows scientists to explore relationships among subcellular components, cells, and cellular networks at unprecedented resolution. Read More > >
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Nitric Oxide and Zinc Demolish Overexcited Neurons

A recent collaboration between NCMIR and the Center for Neuroscience and Aging at the Burnham Institute demonstrated a unique form of cross-talk between nitric oxide and zinc apoptotic signal transduction pathways that may contribute to neurodegeneration. Read More > >
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Purkinje Cell's Microenvironment May Be Regulated by Cerebellar Structure

A recent collaboration between NCMIR and the New York University Medical Center found that a cerebellar structure called the pinceau may regulate the microenviroment of the initial segment of the Purkinje cell axon. Read More > >
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Astrocytes Change During Postnatal Brain Development

Unique astrocyte territories in the adult brain are likely formed through competition between astrocyte processes, similar to the competitive interactions among neuronal dendritic fields, according to a recently published study by NCMIR researchers Eric A. Bushong, Maryann E. Martone, and Mark Ellisman that examined the fine morphological features of developing astrocytes in the rat brain. Read More > >
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NCMIR Scientist Places in Nikon's Small World Competition

NCMIR’s Tom Deerinck placed fourth in Nikon's 2003 Small World Competition with his image of a section of rat hippocampus stained with various cellular markers and imaged using 2-photon fluorescence microscopy. This is Deerinck's second win in this competition in as many years. Read More > >
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EM Tomography Emerges as a Useful Tool for Studying the Nervous System

These images, featured on the July 2003 cover of Microscopy Today, demonstrate the emerging importance of electron tomography as a research tool, particularly for studying the nervous system. Read More > >
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Relationship of Astrocytes to Laminar Boundaries in the Adult Brain Examined

The relationship of astrocytes to laminar boundaries in the adult brain was examined in a study published in the Journal of Comparitive Neurology. In this image, a protoplasmic astrocyte has been filled with a fluorescent dye (yellow) and the surrounding tissue is labeled for EphA4 (blue), revealing one of the laminar boundaries. Read More > >
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NCMIR Scientist Wins First in Nikon Small World Competition

Tom Deerinck’s photomicrograph of a sagittal section of rat cerebellum placed first in the 28th Annual Nikon International Small World Competition. Fluorescence and confocal microscopy were used to achieve this image. Read More > >
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Connexin Trafficking Imaged Through Multicolor and Electron Microscopy

An optical section of double-labeled (FlAsH green and ReAsH red) gap junctions in HeLa cells is pictured. The tubulin network is shown in white, and the cell nuclei is shown in blue. Read More > >
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Synaptic Carbohydrate Antigen Plays Key Role in Neuromuscular Synapse Development

This laser scanning confocal image (BioRad Radiance confocal) is of a group of neuromuscular junctions from the mouse gastrocnemius muscle. The sample was triple labeled for acetylcholine receptors (red), synaptophysin (green), and neuron-specific enolase (blue). Read More > >
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NCMIR Pioneers Use of Eosin for Fluorescence Photooxidation as a Staining Technique

A projection of a series of optical sections through a Purkinje neuron reveals both the overall morphology (red) and the dendritic spines (green). The unconjugated red dye fills the entire dendritic tree when injected, including shafts and spines. In contrast, the phalloidin-Alexa 488 conjugate selectively labels the spines. Read More > >
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3D Image of Dendritic Spines Provides New Information on the Actin Cytoskeleton

Three-dimensional reconstruction of labeled spines using electron tomography showed that the labeled dense material was in continuity with the post-synaptic density. These results highlight differences in the actin cytoskeleton between different spine populations and provide novel information on the organization of the actin cytoskeleton in vivo. Read More > >

In the News

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New Focal Charge Compensation Mode for ZEISS Field Emission Scanning Electron Microscopes Improves Image Quality

In collaboration with the National Center for Microscopy and Imaging Research (NCMIR) at the University of California San Diego, ZEISS (www.zeiss.com) released a new Focal Charge Compensation module for block face imaging with ZEISS GeminiSEM and 3View® from Gatan.

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New 3D Imaging Reveals How Human Cell Nucleus Organizes DNA and Chromatin of it’s Genome

In a new paper, published in the July 28, 2017 online issue of Science, a team of researchers at the University of California San Diego School of Medicine and the Salk Institute for Biological Studies, describe development and application of new electron microscopic imaging tools and a selective stain for DNA to visualize the three-dimensional structure of chromatin.

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Merry Microscopy and Happy New Technique!

Multi-color electron microscopy featured in NIH Director's Blog post commemorating the holiday season and the December tradition that sparked the idea.
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Electron Kaleidoscope: New Technique Visualizes Multiple Objects in Many Colors

Ability to see beyond the grayscale promises future of revelations.

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NCMIR Wins Prestigious NIH Scientific Visualization Competition

NCMIR team wins top prize in NIH “Beauty of Science” art competition for visualization related to glaucoma therapy.    

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NCMIR Aids UCSD Investigators in the Development of a Bioinspired Design for a New Space Exploration Device.

Using microCT, NCMIR researchers helped investigators from the laboratory of Joanna McKittrick at UCSD to model and analyze the 3D geometry of the sea urchin mouthpiece.  This highly accurate biological model was then used as a basis for the design and development of prototype claw device for robotically gathering soil samples.

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NCMIR Images Smallest-yet Bacterial Genome Designed and Synthesized by Venter Institute

NCMIR scientists worked with J. Craig Venter and his team at the J. Craig Venter Institute (JCVI) to characterize the genome segment sizes and ultrastructures of JCVI-syn3.0 cells.  JCVI-sny3.0 is a minimalist genome fully designed and synthesized by the team at JCVI that includes only the genes essential to support life.

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NCMIR Investigator Receives Young Researcher Award for Work on Fragile X Syndrome

On March 17, 2016, Matthias Haberl, Ph.D., a postdoctoral researcher at NCMIR, received a Young Researcher Award from the Jerome Lejeune Foundation associated with his doctoral research in Fragile X syndrome.  Fragile X syndrome is the most common inherited form of intellectual disability and a frequent cause of autism spectrum disorder.  Haberli and colleagues in the laboratory of Andreas Frick found changes in the brain wiring that provide a potential explanation for the underlying sensory symptoms.

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$3 million grant enables nucleome imaging research at NCMIR/CRBS and the Salk Institute

Under its new 4D Nucleome Program, the National Institutes of Health (NIH) Common Fund has awarded three grants totaling more than $30 million over five years to multidisciplinary teams of researchers at University of California, San Diego.  One of the three initiatives awarded to UCSD— called Imaging Tools — involves Mark Ellisman, PhD, Distinguished Professor of Neurosciences and director of the Center for Research on Biological Systems at UC San Diego, together with project lead Clodagh O’Shea, PhD, at the Salk Institute for Biological Studies. The two institutions will receive a total of $3 million over five years to create genetically encoded metal nanoparticles and novel paints that will act as molecular beacons to light up genes of interest within the maze of DNA, enabling their structures to be visualized.

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NCMIR’s own Picture Wizard Tom Deerinck featured in the January issue of “The Scientist” magazine

NCMIR researcher Tom Deerinck was profiled by writer Jef Akst in the January 2015 issue of the magazine “The Scientist”.   Deerinck is a completely unique individual with a novel career history of creating high works of arts from his impeccable scientific studies. The magazine profile details how he came to work when he was 20 years old under the tutelage of distinguished professor Mark Ellisman at UCSD in 1978 as well as how his passion for the scientific process and imaging on state-of-the-art microscopes endures.

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NCMIR researcher captures second place in the 11th annual Olympus BioScapes International Digital Imaging Competition

Winners of the annual Olympus BioScapes Competition were announced December 16, 2014, and NCMIR researcher Thomas Deerinck garnered second place for his triple labeled confocal fluorescence image of cerebellar Purkinje neurons in rodent brain. The competition, which is widely recognized as one of the preeminent photography competitions focusing on microscopic imaging in the life sciences, attracted over 2500 entries from 70 different countries throughout the world.

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UC San Diego and NCMIR Researcher Roger Tsien is awarded the first annual Golden Goose Award from Congress

PhD, Professor of Pharmacology at UC San Diego and Nobel laureate for Chemistry 2008, for work related to NCMIR at UC San Diego, received the Golden Goose Award in September 2012. This award “showcases researchers who pursue oddball topics that eventually lead to significant health and economic benefits, the awards were created by a coalition of science organizations (including AAAS, publisher of Science Insider) Read More > >
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The Microscopy Society of America awards the Maser Award to NCMIR’s own Gina Sosinsky

At the 2012 Microscopy & Microanalysis meeting held in Phoenix this July, Gina Sosinsky, Assistant Director of NCMIR and a UCSD Professor-In-Residence in Neurosciences was awarded the Morton D. Maser Ward for Distinguished Service to the Microscopy Society of America. This major society award recognizes outstanding volunteer service to the Society. Read More > >
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NCMIR Commissioned to Provide Artwork for the New Medical Education and Telemedicine Center at UCSD

Researchers from the National Center for Microscopy and Imaging Research (NCMIR) have been charged with providing science-based artwork for the public areas of the new +100,000 square foot Medical Education and Telemedicine Center on the campus of the School of Medicine at UCSD. The new center will be a hub of learning that incorporates state-of-the-art design and technology to prepare medical students to become physicians and innovators of tomorrow. It will also be used for physicians to learn new skills utilizing the latest advances in medical and surgical technology, such as surgical robotics.

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Two Top Biological Imaging Centers Offer Powerful Free Online Tool to Researchers, Educators, and Public

ASCB’s The Cell: An Image Library and NCMIR’s Cell Centered Database introduce new interface to spur health discoveries and science education The collaboration of two leading cell image resource centers now provides a more extensive and advanced facility for archiving, sharing, and analyzing microscope images in great detail. The American Society for Cell Biology (ASCB) and the National Center for Microscopy and Imaging Research (NCMIR) at the University of California, San Diego (UCSD), have joined forces to provide a unified interface. This union extends ASCB’s The Cell: An Image Library website with new capabilities and an extensible software infrastructure. Read More > >
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Waitt Family Foundation Project Develops Whole Brain Catalog

At the year’s biggest international meeting of neuroscientists, researchers from the University of California, San Diego will unveil a tool that could revolutionize the way scientists and students explore and map the mysteries of the brain. Read More > >
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2008 Nobel Prize in Chemistry Shared by UC San Diego and NCMIR Researcher Roger Tsien

University of California, San Diego Professor Roger Tsien, Ph.D., will share the 2008 Nobel Prize in Chemistry with Osamu Shimomura of the Marine Biological Laboratory in Woods Hole and Boston University School of Medicine, and Martin Chalfie of Columbia University in New York. Read More > >
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Former NCMIR Project Scientist Awarded Society for Histochemistry's Feulgen Prize

Dr. Ben Giepmans, former NCMIR project scientist, was awarded the Society for Histochemistry's Feulgen Prize for his outstanding contributions to the development and application of new advanced fluorescent proteins and biarsenical-tetracysteine probes for light and electron microscropy. Read More > >
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NCMIR Scientist Wins Title of Top Science Photographer of the Year in the World Photography Awards

CMIR scientist Thomas Deerinck captured first place in the inaugural Sony World Photography Awards in the Professional Science Photography category announced at a VIP gala ceremony at the Palais des Festivals in Cannes, France. Read More > >
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Ellisman Gives Featured Lecture on Emerging Technologies at Society for Neuroscience 2007

Innovative efforts underway at UCSD's School of Medicine to leverage telecommunications and information technologies for accelerating biomedical research were featured during a special lecture during the 2007 annual Society for Neuroscience conference. UCSD's track record of driving the development of digital age technologies for acquiring, visualizing, and communicating research information was highlighted in a special lecture delivered by Dr. Mark Ellisman, of the University of California, San Diego. being conducted all this week at San Diego's Convention Center. Read More > >
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NCMIR Researcher is Helping to Bridge Art and Science Through the Use of Dynamic Media

Ruth West, director of visual analytics and interactive technologies at NCMIR and a team of engineers, computer scientists, biologists, and artists have created interactive artwork for exploring new ways of representing nature in the era of metagenomics. Viewers can interact real-time with genetic sequences of marine microorganism on CalIT2's 100-million-pixel autosterographic display. The immersive visualization display is titled ATLAS in silico and is on display August 4-6 at UCSD's CalIT2 as part of the annual SIGGRAPH conference that features cutting-edge computer graphics and interactive technologies. Attendance at this year's conference is expected to attract 25,000 to San Diego. Read More > >
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UCSD to Acquire Cutting-Edge Electron Microscope for Biomedical Research

UCSD's National Center for Microscopy and Imaging Research (NCMIR) has been awarded a large grant to assist in the purchase of a new high energy electron microscope. Today's announcement by the National Center for Research Resources (NCRR), a part of the National Institutes of Health (NIH), will afford NCMIR scientists an opportunity to explore new microscope technologies for advancing research benefiting biomedical research. UCSD's award is the only grant this year for an advanced electron microscope from NIH's High-End Instrumentation (HEI) program. Read More > >
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NCMIR scientist selected to judge the annual Nikon Small World Photomicrography Competition

Nikon Instruments Inc. has announced the judging panel for the 33rd International Small World Photomicrography Competition. The panel includes Thomas Deerinck, a Research Scientist at the National Center for Microscopy and Imaging Research at UCSD. The other judges chosen by Nikon for this year’s competition include John Hart, an Atmospheric and Oceanic Science Professor at University of Colorado; Malcolm Ritter, AP Science Writer; Daniel Sieberg, Science & Technology correspondent for CBS News; and Nicole Dyer, Senior Editor at Popular Science. Read More > >
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NCMIR-Osaka Team Among Finalists in SC06's High Performance Computing Analytics Challenge<

NCMIR’s “Computational Oral and Speech Science on E-science Infrastructure” team will face off against other finalists in the SC06 High Performance Computing (HPC) Analytics Challenge, during a special session of the annual Super Computing Conference on November 14thSC06 is the premier international conference on high performance computing, networking and storage. SC06 will be held November 11-17, 2006, in Tampa, Florida. Read More > >
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NCMIR scientist wins first place in the 2006 Olympus BioScapes International Digital Imaging Competition

A strikingly colorful light microscopic image of mouse retina has earned first place for NCMIR scientist Thomas Deerinck in the 2006 Olympus BioScapes Digital Imaging Competition. The quadruple-fluorescence confocal image, taken as part of a study on neurofibromatosis, shows the highly complex organization of some of the different cell types present in the retina. Read More > >
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NCMIR, NBCR, CalIT2, and EVL demonstrate integrated environment for the development of multiscale, multimodal, multi-site science at SC06

Collaborators from the National Biomedical Computation Resource (NBCR), the California Institute for Telecommunications and Information Technology (CalIT2), the University of Illinois' Electronic Visualization Laboratory (EVL), and NCMIR demonstrate how researchers at multiple locations can take advantage of advanced networks, software, and computational resources to extend the capabilities of bioscience instrumentation and informatics at the 2006 Super Computing Conference. Read More > >
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NCMIR-Osaka Team Among Finalists in SC06's High Performance Computing Analytics Challenge

Kazunori Nozaki and Susumu Date, of Osaka's Graduate School of Information Science and Technology, and colleagues from Japan and NCMIR will face off against other finalists in the SC06 High Performance Computing (HPC) Analytics Challenge, during a special session of the annual Super Computing (SC) Conference on November 14th. The premier international conference on high performance computing, networking and storage, SC06 will be held November 11-17, 2006, in Tampa, Florida. Read More > >
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Ellisman presents NCMIR research to Japanese Royals

At the invitation of Japan’s Emperor Akihito, Mark Ellisman presented an overview of NCMIR’s research on multi-scale imaging and multi-scale modeling of the nervous system. Ellisman presented a multimedia poster and summarized research advances made possible by an alliance of leading researchers in biology and brain research, as well as advanced computing technologies. Read More > >
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Bright future — Rapid advances in fluorescent tools promise to illuminate the details of protein expression, activity, and function

An interdisciplinary team of biological imaging experts from the University of California San Diego (National Center for Microscopy and Imaging Research, Pharmacology Dept., Chemistry and Biochemistry Dept., and the Howard Hughes Medical Institute) recently contrasted the characteristic benefits and limitations of many new classes of fluorescent probes for studying proteins. Sharing the perspective that major advances in the life sciences are strongly tied to the ability to directly observe dynamic processes in living systems, and to localize the responsible molecular machinery in situ by electron microscopy, they published a review of relevant fluorescent imaging technologies in the 14-April-2006 issue of Science. Read More > >
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Studies of mouse models of human disease helped by NCMIR's large-scale imaging expertise

Scientists studying the nervous system have long struggled to understand how higher order structures, such as cellular networks, are assembled out of finer building blocks, such as dendritic and axonal architectures. Mapping the entire neural structure is the key to elucidating brain function. In a forthcoming issue of Neuroinformatics, a team of NCMIR researchers report on their progress towards this central goal by describing new procedures to study brain architecture and to characterize pathological changes in transgenic mice, spanning millimeter- to nanometer-sized structures. Read More > >
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IBM's online series highlights NCMIR's Telescience technologies

When IBM seeks an authority on Grid-computing, they look to UCSD researchers. NCMIR's Abel Lin has authored a tutorial, "Building a Unified Grid" for IBM's authoritative online reference, DeveloperWorks. In this multi-part series, Lin details how Telescience's Grid-based system architecture for science, developed at NCMIR over the past 20 years, is helping to blaze trails for Grid-developers outside of the ivory tower. Read More > >
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NCMIR researcher wins second and eighth place in the Nikon International Small World Competition.

Nikon Corp has announced the winners of the 2005 Nikon International Small World Competition. Local NCMIR scientist Tom Deerinck garnered a second and an eighth place in the prestigious competition with his images of tissues stained with fluorescent quantum dots Read More > >
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Science Features Collaborative Study Between NCMIR and Salk Institute

In a collaboration between computational neuroscientists and neuroanatomists, researchers have created a 3-D, nano-scale “anatomically correct” neuronal synapse that provides new insights into the way synapses work. Scientists combined biology, high-voltage electron microscopy, and computer modeling to view ectopic neurotransmission. Read More > >
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Science Highlights CCDB in "NetWatch"

The Cell Centered Database (CCDB) was featured in the journal Science's "NetWatch" column, which named the site as a novel way of making microscopic imaging data available to the science community. The article, which appeared in the March 25 issue, highlighted the CCDB's multidisciplinary appeal, as it benefits a broad range of scientists from "anatomists charting the nuances of neuron branching to modelers hoping to devise more realistic cell simulations." The CCDB is open to any researcher who wishes to contribute data. Read More > >
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NCMIR Featured in Bio-IT World

NCMIR’s “BioWall,” a newly designed 20-tile wall of high-resolution flat-panel displays that project massive, detailed 2D and 3D images of the brain, was featured in Bio-IT World this month. Read More > >
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Rat Cerebellum Image Wins Light Microscopy Award

NCMIR microscopist Thomas Deerinck's image of a rat cerebellum won fifth place in the Olympus Bioscapes International Digital Imaging Competition. The image, a photomicrograph of a section of rat cerebellum, was achieved using Quantum Dot technology and multiphoton microscopy. Read More > >
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NCMIR, BioWall Featured in The Scientist, San Diego Union-Tribune, and TechTarget

CMIR's newly constructed BioWall tiled display, a 20-tile wall of flat-panel displays that project massive, detailed 2D and 3D images of the brain, has been featured in a variety of publications in recent months. Read More > >
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Undergrads Explore NCMIR Cyberinfrastructure in Japan

As part of a National Science Foundation (NSF) project that prepares engineering students for the global workforce, two UCSD undergraduates are spending their summer enhancing NCMIR's cyberinfrastructure at Japan 's Osaka University. Stephen Geist and Ramsin Khoshabeh, under the tutelage of NCMIR's Mark Ellisman, Steven Peltier, and Tomas Molina, are exploring NCMIR's Telescience in collaboration with researchers from the Cybermedia Center at Osaka University. Read More > >
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NCMIR Represented at Microscopy and Microanalysis 2004

The annual Microscopy and Microanalysis conference featured NCMIR researchers demonstrating advances in imaging techniques. Dr. Diana L. Price's poster presentation, titled "Application of a Multi-Photon High-Resolution Large-Scale Montage Imaging Technique to Characterize Transgenic Mouse Models of Human Neurodisorders," won this year's M&M Traveling Poster Award. The study revealed neuropathology in the hippocampus and cerebellum of the Parkinsonian mouse brain, two areas often overlooked in Parkinson's disease research. Read More > >
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U.S. and Korean Research Institutions Link Laboratories to Advance Microscopy and Information Technologies

Korean delegates from the Korean Basic Sciences Institute (KBSI) joined UCSD Chancellor Robert Dynes and NCMIR Director Mark Ellisman to sign a Memorandum of Understanding (MoU) promoting international cooperation in information technology, advanced analytical imaging, and biomedical research. This July, that understanding will become accomplishment as NCMIR begins testing the boundaries of its Telescience; technologies on Korea's new 1.25 MeV ultra high-voltage electron microscope. Read More > >
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Telescience Enlisted in Fight Against SARS

Since February, more than 8000 cases of Severe Acute Respiratory Syndrome (SARS) and 600 deaths have been reported to the World Health Organization. When researchers from Taiwan, one of the hardest hit regions, began looking for ways to help combat the spread of the virus, they recognized the potential value of Telescience technologies developed by UCSD affiliates, and contacted NCMIR for help.

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Telescience Recognized for Facilitating Biomedical Research on a Global Network

Telescience participants at Supercomputing 2003 demonstrated remote microscope manipulation, high bandwidth over the next generation Internet protocol (IPv6), and Web portal options for collaborative international research. Telescience won "Best Application" during the annual Bandwidth Challenge. Read More > >
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NCMIR Exhibits Remote Control Microscopy in Europe

Scientists in Belgium operated NCMIR's electron microscope in San Diego via the Internet as part of an international forum to promote global research networking. At The Global IPv6 Service Launch Event in Brussels, Belgium this January, NCMIR researchers in San Diego invited Belgian scientists to manipulate remotely their high-performance electron microscope to examine a tissue sample from a mouse hippocampus cortex. Read More > >