Cellular Dynamics


The Oosight(R) product line of microscopes, developed at the MBL  and commercialized by Cambridge Research & Instrumentation, Inc. (CRi), has been acquired by Hamilton Thorne, Ltd., a provider of precision laser devices and image analysis systems for the fertility, stem cell, and developmental biology research markets.

Widely used in fertility clinics to assess the health of unfertilized eggs (oocytes), the Oosight system provides live, high-contrast images and captures quantitative data on important oocyte structures using a patented, non-invasive, polarized-light technique. The technology was developed at the MBL by Rudolf Oldenbourg, Michael Shribak and colleagues in the 1990s and 2000s and commercialized by CRi as LC-PolScope(TM) technology. The Oosight system’s visualization capabilities have enabled breakthroughs in assisted reproductive technology, stem cell generation, and developmental biology research.

Visualization of the meiotic spindle in a rhesus monkey oocyte (egg) using the OosightTM spindle imaging system during enucleation. The spindle is near the 12 o'clock position in the egg. Credit: From Byrne, et al. 2007. Nature 450: 497-502 (Supplementary Material).

Visualization of the meiotic spindle in a rhesus monkey egg using the Oosight spindle imaging system during enucleation. The spindle is near the 12 o’clock position in the egg. Credit: Byrne et al (2007) Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature 450: 497-502.

“The Oosight system is a unique instrument that is complementary to our laser products in both fertility and developmental biology research labs,” remarked David Wolf, President and CEO of Hamilton Thorne. “As a long-term distributor of the Oosight system we have already completed the technical integration of the Oosight with our laser products. We believe that by leveraging our established, world-wide sales channels and investing in product marketing, we can generate incremental sales of the Oosight product.”

Additional information on the Oosight product and its multiple applications can be found at www.hamiltonthorne.com/index.php/oosight-overview.

 

MBL Adjunct Scientist Amy Gladfelter can now add “video producer” to her resume. Tapped to make her science “visible to the world” by Celldance Studios, a project of the American Society for Cell Biology (ASCB), Gladfelter came up with an aesthetically beautiful, simply told video about her discoveries of what goes wrong when cells form toxic aggregates, such as in Alzheimer’s disease. Her mini-movie, called “Companions in Discovery,” was filmed partly at MBL and partly at Dartmouth College, where she is an Associate Professor of Biological Sciences. It premiered for an appreciative audience in December at the ASCB annual meeting in Philadelphia.

“I like the end of the film, where members of [Gladfelter’s] lab talk briefly on camera. These young faces are the future of cell biology,” said Simon Atkinson, chairman of the ASCB’s Public Information Committee, which sponsors Celldance Studios.

Celldance Studios gave Gladfelter $1,000 to underwrite her costs, and provided video editing and post-production support. The original score is by Hollywood film composer Ted Masur, son of cell biologist Sandra Masur. More information is here.

 

A thin crescent of ice was still on Eel Pond when Pablo Correa came to the MBL last March to begin shooting a video. Correa’s visit was exploratory: He knew he wanted to make a short documentary about the MBL, but hadn’t defined a focus beyond the diverse animals maintained in the Marine Resources Center. Correa spent several days shadowing David Remsen, manager of the Marine Resources Department, and his staff, and he took an early-season sail with them on the MBL’s collecting boat, the Gemma. He also observed several MBL scientists who use marine animals as model organisms in their research.

The video Correa ended up making, “These Eyes Follow the Moon,” is not a typical documentary. It is nearly wordless and impressionistic. Yet it also captures an essential “feeling” about the MBL. It moves from the wide-open spaces of the MBL’s ocean setting to the quiet, focused concentration in labs where instruments are prepared for the microscopic imaging of cells. The video also reflects the rhythm of Marine Resources just as the collecting season starts up in early spring. (The MBL collects marine organisms for biological research from April through December, with August being the high season when squid and many other species are collected daily. “August is also the time of year when anything unusual starts to show up in the nets,” Remsen says.)

Correa is editor of the science section of El Espectador, a daily newspaper with national circulation based in Bogotá, Colombia; and a free-lancer for SciDev.net, a network that publishes science news from developing countries. He was a fellow in MIT’s Knight Science Journalism program in 2012-2013.

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Featured in this video are:

In the Marine Resources Center: Skate (Rajidae) at 0:06, 0:24 and 0:33; spider crabs (Libinia) at 3:30; scup (Stenotomus) at 3:40; spiny dogfish (Squalus ) at 4:10; seahorse (Hippocampus) at 4:16. At 4:30, Dave Remsen describes the eyes of the horseshoe crab (Limulus). At 5:30, cuttlefish (Sepiida) for the study of cephalopod camouflage in Roger Hanlon’s laboratory.

Movie of squid skin at 6:27 by Trevor Wardill and Paloma Gonzalez-Bellido: Confocal z-stack of squid skin, blue and green colors showing tissue auto fluorescence and Lucifer yellow forward filled neurons shifted to red using antibodies.

Gonzalez-Bellido PT and Wardill TJ (2012). Labeling and confocal imaging of neurons in thick invertebrate tissue samples. Cold Spring Harb Protoc: doi:10.1101/pdb.prot069625

Movie of dividing cells at 7:20 by James LaFountain and Rudolf Oldenbourg: The events of cell division during meiosis I in a living insect spermatocyte. Testes from the Crane fly Nephrotoma suturalis were observed with time-lapse liquid crystal polarized light microscopy (LC-PolScope, MBL, Woods Hole MA, and PerkinElmer, Hopkinton MA). Movie images display the naturally occurring birefringence of cell organelles and structures that are made up of aligned molecules, such as the meiotic spindle and mitochondria. Horizontal image width is 56 µm.

By Jane MacNeil

MBL Distinguished Scientist Shinya Inoué has been designated as the second Honorary Scholar within the Edward Sylvester Morse Institute at the University of Washington.

This designation honors Inoué’s interactions with the university’s Friday Harbor Laboratories (FHL) during the 1950s and beyond, and recognizes his considerable scholarly, research, and educational contributions to the imaging and understanding of cell development in marine organisms.

Friday Harbor Laboratories, the University of Washington’s marine station on San Juan Island. Photo courtesy University of Washington.

Friday Harbor Laboratories, the University of Washington’s marine station on San Juan Island. Photo courtesy University of Washington.

The award was bestowed on Inoué by M. Patricia (Trish) Morse, one of the co-founders of the E.S. Morse Institute’s scholarly exchange program between Japanese marine laboratories and the Friday Harbor Laboratories. Trish Morse is a distant relative of Morse’s and the first native of Woods Hole to receive a PhD in marine zoology.

Inoué’s connection to FHL began when, after graduating from Princeton with a Ph.D. in Biology in 1951, he took his first professional appointment as an Instructor in the Department of Anatomy at the University of Washington. During spring break of 1952, he drove two hours north and took the Puget Sound ferry to Friday Harbor for the first time where, to his delight, he was able to collect more than four species of jellyfish right off the dock in front of the lab. Furthermore, Inoué recalls, the lab had running seawater piped through Pyrex glass tubing that was so pure and free from excess heavy metal ions that not only sea urchins, but 100 percent of the jellyfish eggs, could be fertilized.

While at Princeton, Inoué had improved upon his hand-built polarized light microscope and in 1951 he used it to prove the universal existence of the spindle fibers, the dynamic protein filaments that move chromosomes in the dividing cells. This was his first major accomplishment in a career devoted to delving into the mysteries of living cells.

“In an attempt to better understand how cells divide, Dr. Inoué made a series of epochal innovations in the development of light microscopy,” said Emperor Akihito of Japan, in 2003, on the occasion of Inoué’s receipt of the International Prize for Biology. “These advances rendered it possible to directly observe dynamic changes in the supramolecular structure of living cells during cell division. This contributed immensely to advancing research in such fields of cell division, cytoskeleton, and cell motility,” the Emperor said. ”The products of Dr. Inoué’s research are widely utilized by researchers around the world and contribute immensely to the advancement of biological sciences.”

MBL Distinguished Scientist Shinya Inoué (front center) and some of the MBL-affiliated cell biologists and biophysicists whom he has influenced (l-r, by row): Ted Salmon and Kip Sluder; James LaFountain, Ron Vale, Gary Borisy, and Michael Shribak; Jason Swedlow, Conly Reider, Rudolf Oldenbourg, Tim Mitchison, and Gaudenz Danuser. Credit: Tom Kleindinst

MBL Distinguished Scientist Shinya Inoué (front center) and some of the MBL-affiliated cell biologists and biophysicists whom he has influenced (l-r, by row): Ted Salmon and Kip Sluder; James LaFountain, Ron Vale, Gary Borisy, and Michael Shribak; Jason Swedlow, Conly Reider, Rudolf Oldenbourg, Tim Mitchison, and Gaudenz Danuser. Credit: Tom Kleindinst

Inoué began coming to the MBL as a visiting investigator in the early 1950s, and became a year-round principal investigator in 1977. He was named MBL Distinguished Scientist in 1986.

The first recipient of the Edward Sylvester Morse Honorary Scholar award was Arthur H. Whiteley, a sea urchin developmental and cell biologist at the Friday Harbor Laboratories for more than 60 years. Previously, Whiteley had been a student of E. Newton Harvey’s at Princeton University, where he received his Ph.D. in 1945 and worked with Inoué’s mentor, Kenneth Cooper. While not classmates, Whiteley and Inoué did become friends while Inoué served as an Instructor at the University of Washington from 1951-1953. Whiteley and his wife, Helen, were both early exchange scholars in Japan and were active supporters of Japanese scholars working on developmental biology at the Friday Harbor Laboratories. Whiteley died in April of 2013 after a long life dedicated to science, education, and international collaboration.

Background on Edward Sylvester Morse

In the 1850s, Edward Sylvester Morse was a protégé of Louis Agassiz, then chair of Zoology and Geology at Harvard University. Under Agassiz’s direction, Morse studied marine biology and specialized in conchology. Morse became one of the leading natural scientists of his time and helped develop the Museum of Comparative Zoology at Harvard. Agassiz’s ties to the MBL include his founding of “a practical school of natural science, especially devoted to the study of marine zoology” on Penikese Island, an institution which is considered to be the precursor of MBL. Morse taught with Agassiz at the Penikese Island school in 1873 and later was a visiting scientist at the MBL.

Morse’s career focused on the study of brachiopods, bottom-dwelling marine animals that have two shells and are considered living fossils. In 1870, he published The Brachiopods, a Division of the Annelida, which attracted the attention of Charles Darwin. In 1876, he was named a fellow of the National Academy of Sciences. Three years later, he visited Japan in search of coastal brachiopods and became the first Professor of Zoology at the Tokyo Imperial University. At the end of his term, he recommended that the Japanese government hire, as his successor, Charles O. Whitman, later to become the founding director of the MBL. Whitman was Professor of Zoology at Tokyo Imperial University from 1879-1881, during which time he was the first professor to introduce systematic methods of biological research, including the use of microscopes, to Japanese students. Whitman went on to become head professor of the Department of Zoology at the University of Chicago where he used the same systematic methods of scientific research and teaching with his students.

While in Japan, Morse became very interested in Japanese ceramics, pottery, and the Japanese way of life. He was president of the American Association for the Advancement of Science from 1886 to 1889, and in 1892 he became the Keeper of Pottery at the Museum of Fine Arts in Boston, a position he held until his death in 1925. His collection of daily artifacts of the Japanese people can still be seen today at the Peabody Essex Museum in Salem, Mass.

Similar to the Order of the Sacred Treasure (3rd class) that Inoué received from the Japanese government in 2010, Edward Sylvester Morse received the Order of the Rising Sun (3rd class) in 1914 and the Order of the Sacred Treasure (2nd class) in 1922.

Senior Scientist Rudolf Oldenbourg and other MBL-affiliated biologists and physicists revealed their collaborative process to create informative, beautiful images of cell structure and behavior at the American Association for the Advancement of Science (AAAS) meeting last weekend in Boston, Mass.

The symposium “Innovations in Imaging: Seeing is Believing” was organized by Amy Gladfelter of Dartmouth College, an MBL Whitman Investigator.

web-GladfelterOldenbourgIma

Fluorescence image of a living cell (MDCK) expressing septin molecules linked to green fluorescent protein (GFP). The image was recorded with the Fluorescence LC-PolScope and shows fluorescent septin fibers in color, indicating that the fluorescence is polarized and the septin molecules are aligned in the fibers. Credit: Rudolf Oldenbourg/MBL

“We are beginning to understand the basis for cell organization at unprecedented spatial and temporal resolution through the creative application of fundamental physics to microscopy,” Gladfelter stated. “This symposium will help motivate the next phase of interdisciplinary approaches to advance the visualization of life, from the scale of a single molecule to the whole organism.”

The data collected in biological images, Gladfelter noted, not only illuminates basic cellular processes, but is useful for medical purposes: to diagnose a metastasizing cancer or microbial infection, for example, or to screen chemical libraries for new pharmaceuticals.

“These images bring us to a beautiful world beyond the grasp of our normal senses,” Gladfelter stated. “In this way microscopes give us beauty and [biological or medical] application, often in the same image.”

The capacity of microscopes to reach beyond the senses is well appreciated by Oldenbourg, who spoke on New Frontiers in Polarized Light Microscopy for Live Cell Imaging.
(Oldenbourg’s MBL co-authors are Michael Shribak, Tomomi Tani, and Shinya Inoué.)

“Polarization is a basic property of light that is often overlooked, because the human eye is not sensitive to polarization. Therefore, we don’t have an intuitive understanding of it and optical phenomena that are based on polarization either elude us or we find them difficult to comprehend,” Oldenbourg stated.

“Like most scientific instruments, the polarized light microscope translates polarization effects so they can be perceived by our senses, in this case by our eyes, and makes them amenable to quantitative and analytical analysis. At the MBL, we are developing polarized light imaging techniques, including fluorescence polarization … for generating time-lapse images that clearly reveal the otherwise invisible dynamics of single molecules and molecular assemblies in organelles, cells, and tissues.”


The events of cell division during meiosis I in a living insect spermatocyte, beginning at diakinesis through telophase to the near completion of cytokinesis. Testes from the Crane fly Nephrotoma suturalis were observed with time-lapse liquid crystal polarized light microscopy (LC-PolScope, MBL, Woods Hole MA, and PerkinElmer, Hopkinton MA). Movie images display the naturally occurring birefringence of cell organelles and structures that are made up of aligned molecules, such as the meiotic spindle and mitochondria. Horizontal image width is 56 µm. Credits: James LaFountain and Rudolf Oldenbourg/MBL

Other talks in the symposium included:

Navigating the Dynamic Cell
Jennifer Lippincott-Swartz (National Institutes of Heath/MBL Physiology Course)

Imaging Three-Dimensional Dynamics in Cells and Embryos
Eric Betzig (Howard Hughes Medical Institute/MBL Physiology Course and MBL Neurobiology Course)

Structured Illumination and the Analysis of Single Molecules in Cells
Rainer Heintzmann (King’s College, London)

Imaging Single Cells in the Breast Tumor Microenvironment
John Condeelis (Albert Einstein College of Medicine)

Single Molecule Imaging in Live Cells
Amy S. Gladfelter (Dartmouth College/MBL Whitman Investigator)

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