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4Pi Microscope Coming to Maine

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BAR HARBOR, Maine, Sept. 9 -- The Institute for Molecular Biophysics (IMB), an interdisciplinary biophysical research program in Maine, has been granted $732,624 by the National Science Foundation to install a 4Pi confocal laser scanning microscope. The 4Pi is the most advanced optical microscope, capable of revealing the nanostructure of genetic material within a cell in three dimensions. It will be the first such instrument in the US, the IMB said.
The 4Pi microscope is made by Leica Microsystems in Mannheim, Germany, based on technology developed by Stefen Hell, head of the nanobiophotonics department at the Max Planck Institute for Biophysical Chemistry in Gottingen, Germany. "4Pi" refers to the unique way in which light is emitted.

The slide shows the 3-D structure of mitochondria in mammalian cells recorded with the Leica TCS 4Pi. Comparison of (a) the 4Pi mode and (b) standard confocal mode. (Image: Copyright Bewersdorf, Hell, Rosenmund, Scmidt; MPI Gottingen, Germany)

4Pi microscopy uses a special phase- and wavefront-corrected double-objective imaging system linked to a confocal scanner to enable 4-7 fold increased axial resolution over confocal and two-photon microscopy. The Leica TCS 4Pi system is now released as a limited special edition to partnering institutions that can provide the necessary technical and application environment to optimally employ the technology.

Once installed at The Jackson Laboratory, the 4Pi microscope will enable the IMB researchers to examine specific structures within a cell -- such as a single gene on a chromosome -- at a resolution four to seven times greater than previously possible.

The IMB brings together expertise in biophysics and engineering at the University of Maine in Orono, molecular and cell biology at the Maine Medical Center Research Institute (MMCRI) in Scarborough and genetics and genomics at The Jackson Laboratory in Bar Harbor. IMB said its goal is to explore the structure and function of genes and chromosomes within cells in order to understand precisely how genes control both normal development and disease.

A surface-reconstructed 3-D image of the GFP (green fluorescent protein)-tagged mitochondrial matrix of a live budding yeast cell. Live cell 4Pi imaging allowed researchers in Germany to study the influence of selected mitochondrial proteins on mitochondrial morphology (Image: Max Plank Society)

"Astronomers have space-based telescopes like the Hubble Space Telescope to understand the history and structure of the universe," said IMB co-director Barbara Knowles of The Jackson Laboratory and the University of Maine. "Physicists have giant particle accelerators to isolate the fundamental elements of energy and matter. Now researchers in genetics and biology have an advanced tool to examine the very structure of the mouse, human and other genomes."

"Imagine looking at a satellite image of your state of such high resolution that you can spot the local college football field," said IMB co-director Michael Grunze, who holds joint appointments with the University of Maine, The Jackson Laboratory and the University of Heidelberg in Germany. "Now, imagine being able to see the football itself in 3-D. The 4Pi represents a comparable increase in resolution, only on a nanoscale."

In addition to applications involving imaging of genes and nuclear structure, the researchers are particularly interested in using this microscope to image large, multimolecular structures migrating within and across the cell membrane. For example, a recent discovery at MMCRI indicates that controlling the migration of fibroblast growth factor can prevent reocclusion of coronary arteries after angioplasty.

The National Science Foundation grant for the acquisition of the 4Pi includes funding for a specialized microscopist, most likely a physicist, to analyze samples on the 4Pi. Grunze anticipates that researchers will be able to send or bring biological samples to the IMB for analysis.

"I see biology moving toward specialized high-tech centers like the IMB, bringing in investigators from all over the world," he said.

Initial funding for the IMB was provided by the NSF’s EPSCoR (The Experimental Program to Stimulate Competitive Research) program, designed to fulfill the NSF mandate to promote scientific progress nationwide.

For more information, visit:
Sep 2004
4piBasic Scienceconfocal laser scanning microscopegenetic materialJackson LaboratoryLeica MicrosystemsMaine Medical Center Research InstituteMax Planck Institute for Biophysical ChemistryMicroscopynanostructureNational Science FoundationNews & FeaturesUniversity of Maine

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