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Contact: Ellen R. Weiss
eweiss@biophysics.org
240-290-5606
American Institute of Physics

Secrets of plague revealed

New, super-resolution microscopy technique, described at Biophysical Meeting in Baltimore, shows how the human innate immune system responds to some bacterial toxins but not others

WASHINGTON, D.C. (March 8, 2011) -- In work that is pushing the "diffraction barrier" associated with microscopic imaging of living cells, researchers at Sandia National Laboratories in Albuquerque, NM demonstrated the power of a new super-resolution microscopy technique called Stochastic Optical Reconstruction Microscopy (STORM), which can simultaneously image multiple molecules in living immune cells.

As described today at the 55th Annual Biophysical Society Annual Meeting in Baltimore, MD, Jesse Aaron and Jerilyn Timlin used this new technique to reveal the changes in the concentration of certain proteins in the membranes of human immune cells that encounter toxins from E.coli and showed that the same changes did not occur in immune cells that encountered toxins from Y.pestis, the bacteria that causes plague.

This work is significant because it addresses how our bodies are often able to naturally fight off some bacteria, such as E.coli, while the bacteria that cause plague are able to circumvent our immune systems. Moreover, this is the first time such differences have been detected because molecular changes like these are too small to be seen by conventional imaging methods, which can only reveal the microscopic world down to what is known as the diffraction limit -- essentially the smallest features of the microscopic world that can be resolved using visible light.

"[This] is a way to image biological samples at resolutions that, historically, were thought to be unachievable," says Aaron, who is a postdoctoral fellow at Sandia.

In particular, they were able to image the organization of a key human receptor protein called TLR4, which adorns the outside of immune cells in the body as they prowl for foreign invaders. These receptors recognize lipopolysaccharide (LPS), a toxic chemical that marks the presence of certain types of bacterial invaders, and the TLR4 proteins are key mediators of our bodies' early, "innate" immune responses to these sorts of bacterial infections.

"A cell membrane is a complex, heterogeneous system, so oftentimes you have many proteins that are interacting with each other simultaneously and the scale of those interactions is way below the diffraction limit," says Jerilyn Timlin, a principal scientist at Sandia National Laboratories. "Until the super-resolution methods were discovered, there really was not a way to visualize those interactions."

Now, by employing a novel, simultaneous dual-color imaging system based on the STORM technique and by using an objective-based TIRF microscope and filter-based image splitter, Timlin and Aaron have imaged how TLR4 receptors is organized after it encounters toxic bacterial LPS.

Resolving these molecular interactions at or below 40 nanometers (about 10 times finer than the highest resolution images that can be obtained with light microscopes), they showed that TLR4 receptors cluster together when they detect the toxin. Moreover they compared this clustering behavior for different types of toxins from different bacteria, including Y.pestis, the bacteria that causes plague.

Say Timlin and Aaron, this difference is evident when you look at the higher resolution, as they did in their study.

When TLR4 receptors encounters the toxins produced by E.coli, for instance, they increase in number and clusters on the cell membrane -- changes that are only detectable below the diffraction limit and are not evident using conventional imaging methods.

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The presentation, "SUPER-RESOLUTION MICROSCOPY REVEALS PROTEIN SPATIAL REORGANIZATION IN EARLY INNATE IMMUNE RESPONSES" by Jesse S. Aaron et al is at 11:45 a.m. on Tuesday March 8, 2011 in Ballroom IV of the Baltimore Convention Center. ABSTRACT: http://tinyurl.com/67ptfqs

This work was supported by the National Institutes of Health through the NIH Director's New Innovator Award Program.

MORE MEETING INFORMATION

Each year, the Biophysical Society Annual Meeting brings together more than 6,000 scientists and hosts more than 4,000 poster presentations, 200 exhibits, and more than 20 symposia. The largest meeting of its type in the world, the Biophysical Society Annual Meeting retains its small-meeting flavor through its subgroup meetings, platform sessions, social activities, and committee programs.

QUICK LINKS

Meeting Home Page: http://www.biophysics.org/2011meeting
General Meeting Information: http://www.biophysics.org/GeneralInfo/Overview/tabid/2062/Default.aspx
Search abstracts: http://www.abstractsonline.com/plan/start.aspx?mkey={FEA830A5-24AD-47F3-8E61-FCA29F5FEF34}

PRESS REGISTRATION

The Biophysical Society invites credentialed journalists, freelance reporters working on assignment, and public information officers to attend its Annual Meeting for free. For more information on registering as a member of the press, please contact Ellen Weiss at eweiss@biophysics.org or 240-290-5606. Also see: http://www.biophysics.org/Registration/Press/tabid/2148/Default.aspx

ABOUT THE BIOPHYSICAL SOCIETY

The Biophysical Society, founded in 1956, is a professional, scientific society established to encourage development and dissemination of knowledge in biophysics. The society promotes growth in this expanding field through its annual meeting, monthly journal, and committee and outreach activities. Its over 9,000 members are located throughout the U.S. and the world, where they teach and conduct research in colleges, universities, laboratories, government agencies, and industry. For more information on the society or the 2011 Annual Meeting, visit www.biophysics.org



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