Secrets of plague revealed

Mar 08, 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 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 -- changes that are only detectable below the diffraction limit and are not evident using conventional imaging methods.

Explore further: Polyethylene mulch, glazing create optimal conditions for soil solarization

More information: 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: tinyurl.com/67ptfqs

Provided by American Institute of Physics

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Researchers Uncover a Secret of the Black Death

Sep 18, 2006

Yersinia pestis, the bacteria that causes plague, is a sneaky little intruder with a remarkable ability to evade the body’s immune system. Upon entering an organism, Y. pestis employs a variety of strategies to slip below ...

Mimic molecules to protect against plague

Jul 04, 2008

Bacteria that cause pneumonic plague can evade our first-line defences, making it difficult for the body to fight infection. In fact, a signature of the plague is the lack of an inflammatory response. Now, scientists have ...

Recommended for you

How photosynthesis changed the planet

Nov 20, 2014

Two and a half billion years ago, single-celled organisms called cyanobacteria harnessed sunlight to split water molecules, producing energy to power their cells and releasing oxygen into an atmosphere that ...

From dried cod to tissue sample preservation

Nov 19, 2014

Could human tissue samples be dried for storage, instead of being frozen? Researchers are looking at the salt cod industry for a potential tissue sample drying technology that could save money without sacrificing tissue quality.

Riding a food fad to an opportunity

Nov 18, 2014

Until a couple years ago, Shaun Paul's knowledge of chia was limited to the kitschy terracotta Chia Pet figurines. But recently, chia seeds, promoted as a nutritional powerhouse, have earned a growing consumer ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.