Columbia University Medical Center

Joachim Frank Awarded 2014 Franklin Medal

Joachim Frank

Joachim Frank

Joachim Frank, PhD, professor of biochemistry and molecular biophysics and Howard Hughes Medical Institute investigator, will be awarded the 2014 Benjamin Franklin Medal in Life Science by the Franklin Institute of Philadelphia.

The award recognizes Dr. Frank for the development of cryo-electron microscopy, for using this technology to investigate the structure of large organic molecules at high resolution, and for discoveries regarding the mechanism of protein synthesis in cells.

The Franklin Institute awards—first presented in 1824—are among the oldest and most prestigious science awards in the world. Previous winners include Alexander Graham Bell, Pierre and Marie Curie, Albert Einstein, and Stephen Hawking. Today the award is presented to researchers in the fields of chemistry, computer and cognitive sciences, earth and environmental science, engineering, life science, and physics.

The award will be presented at a ceremony at the Franklin Institute on April 24, 2014.

 

Frank’s Techniques Reveal Hidden World of Molecules

Dr. Frank, who joined Columbia in 2008 from the Wadsworth Center in Albany, originally trained as a physicist and became an expert in the analysis of images taken with the electron microscope. Electron microscopy makes it possible to capture the image of objects too small to be seen by light microscopes.

Electron microscopes allow us to see objects, like this flu virus, that are invisible with light microscopes. Photo: National Institute of Allergy and Infectious Diseases.

Electron microscopes allow us to see objects, like this flu virus, that are invisible with light microscopes. Photo: National Institute of Allergy and Infectious Diseases.

Viruses, proteins, and even atoms are visible with today’s electron microscopes. But even though a single “snapshot” from an electron microscope creates a wonderfully detailed image, that image is only two-dimensional. Biologists must see all three dimensions to understand how a molecule works.

That’s fairly easy when the object is inert. To create a 3-D reconstruction of an object, multiple shots are taken of the object from different angles and then mathematically melded together into a single 3-D image. But that technique does not work for biological molecules, because the powerful electron beam used during the imaging process incinerates the fragile molecules after just a few shots.

The solution to the problem came from Dr. Frank, who had the idea of creating a 3-D image of a molecule by taking shots of thousands of identical molecules lying in different orientations and then combining them. In the late 1970s, Dr. Frank developed the necessary computational methods for reconstructing biological molecules from thousands of images, still employed today by most structural biologists who use electron microscopy.

Dr. Frank used the methods to reveal the 3-D shape of ribosomes, complex molecules that act like factories of the cell, synthesizing all of the cell’s proteins. Combining his mathematical methods with techniques that freeze the molecules in a thin layer of liquid ice (the cryo- in cryo-electron microscopy), he obtained the first 3-D image of the ribosome that clearly showed its two separate subunits and, later, an even more detailed image that gave researchers new insights into how the ribosome works.

Methods devised by Joachim Frank turn images like this – showing the blurry outlines of hundreds of individual ribosomes at different angles – into finely detailed 3-D images. See below.

Methods devised by Joachim Frank turn images like this—showing the blurry outlines of hundreds of individual ribosomes at different angles—into finely detailed 3-D images. See below.

Since then, higher-resolution cameras and faster and more powerful computers have advanced electron microscopy to the point where it’s capable of revealing molecular details down to the size of an atom, putting the method on an equal footing with X-ray crystallography.

Dr. Frank has continued to innovate to gain more insight into how molecular machines accomplish their tasks. He has invented methods that allow biologists to use a single sample of molecules to capture all the different shapes a molecule takes as it performs its function.

In Dr. Frank’s own work with ribosomes, he has used this “story in a sample” approach to look at how ribosomes interact with other molecules during the different steps of protein production. Like multiple still shots for a movie, his studies have revealed how one subunit of the ribosome rotates back and forth in a ratcheting motion to add amino acids during protein production, a process that is the same in all kingdoms of life.

A view of the ribosome from T. brucei, the parasite that causes African sleeping sickness. The structure reveals parts of the ribosome that could be targeted to kill the parasite. Image: Joachim Frank and Yaser Hashem.

A view of the ribosome from T. brucei, the parasite that causes African sleeping sickness. The structure reveals parts of the ribosome that could be targeted to kill the parasite. Image: Joachim Frank and Yaser Hashem.

Basic studies of how the ribosome works in general have recently led to discoveries that may lead to better drugs for certain diseases. In a 2013 Nature paper, Dr. Frank’s team uncovered unique details of the ribosome from the parasite that causes African sleeping sickness, details that may lead to new drugs to kill the parasite. Another 2013 Nature paper revealed how viral RNA commandeers the ribosome of the virus’s host to produce new viruses.

For his accomplishments in electron microscopy, Dr. Frank was elected in 2006 to the prestigious National Academy of Sciences and the American Academy of Arts & Sciences; shared the Elizabeth Roberts Cole Award of the Biophysical Society for developing methods of 3-D reconstruction of biological macromolecules; and was elected a Fellow of the American Association for the Advancement of Science and of the Biophysical Society.

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