Picture perfect

CAMBRIDGE, Mass. — According to Paul Matsudaira, looking at a protein isn’t too different from looking at Mars. The rusty tint from our celestial neighbor becomes blurred as the light travels through the earth’s atmosphere, and what reaches the lens of the telescope is at best a distorted image.

High-resolution microscopes give biologists the same sort of grief. The most infinitesimal changes in temperature of the room or vibrations from a truck rumbling down the street can distort the image. Even the scientist peering at the specimen poses a problem. “You and I are BTU-producing machines,” says Matsudaira, a Whitehead Member, professor of biology, and professor of bioengineering at MIT. “We’re constantly giving off heat.”

But Matsudaira and researchers at Massachusetts Institute of Technology have found a way to take protein pictures that doesn’t require triage.

Deep in MIT’s labyrinthine campus, the Whitehead/MIT BioImaging Center, a collaboration launched a few years ago with seed funding from the W. M. Keck Foundation, and headed by Matsudaira, has set up its new digs. Right in the middle, sequestered in a specially designed, environmentally isolated room, is the Center’s prize possession: a $2M cryoelectron microscope, the JEOL 2200FS.

The first one of its kind in the world for biology problems, the microscope is designed to image the smallest biological molecules at near-atomic resolution, surpassing what most other microscopes can offer.

Like all electron microscopes, this one images electrons as they pass through an object. Placing the microscope in a climate-controlled room isolated from vibrations, magnetic fields, and even people—the microscope is operated remotely—helps stabilize these easily perturbed electrons, thus improving image quality. In spite of these environmental safeguards, some electrons lose energy simply by colliding with atoms, often clouding the image that the microscope detects. A built-in energy filter acts as a sort of funnel, collecting only the electrons that have not lost energy. Put another way, it only photographs electrons that are in focus. Knowing a protein’s shape is intrinsic to understanding its function, so this sort of imaging makes for more than just a pretty picture.

Although a handful of other microscopes in the world are capable of imaging at such a resolution, the lack of an energy filter forces a reliance on computer applications to complete the images. Says Matsudaira, “This one just doesn’t have to work as hard as the others to get the same results.”

The origin of this microscope—and of the Bioimaging Center in general—goes back to conversations between Matsudaira and former Whitehead Member Peter Kim in the early 1990s. After comparing the limitations of X-ray crystallography with the emergence of electron microscopy, the two realized that the latter technology would be crucial in the near future for imaging cellular molecules. The Center, which is under the umbrella of MIT’s school of engineering, also is focusing on other areas of biological imaging in which researchers can view molecular processes in cells and tissues, even tracking protein molecules in 3-D and 4-D, or screening the thousands of cells with automated microscopes.

Matsudaira’s next step will be to beef up the computational infrastructure that all this enormously rich image data will require, particularly as the center begins collaborating with corporate partners.

According to Karen Smith Drew, senior officer for Whitehead’s office of Institutional Advancement, “Whitehead has a strong history of leveraging individual, corporate, and foundation support to enable researchers to break new ground. Paul and I are looking forward to bringing this next opportunity to the attention of our partners.”

Contact

Communications and Public Affairs
Phone: 617-452-4630
Email: newsroom@wi.mit.edu

Related News