(Press-News.org) 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.
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WASHINGTON, D.C. (March 8 2011) -- Researchers at the Instituto de Medicina Molecular in Lisbon, Portugal and the Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil, are making major strides toward understanding the life cycle of flaviviruses, which include some of the most virulent human pathogens: yellow fever virus, Dengue virus, and the West Nile Virus, among others.
Today, at the 55th Annual Meeting of the Biophysical Society in Baltimore, MD, members of the team will report on studies using dengue virus as a model to elucidate the molecular details ...
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"We would like to find a way ...
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Led by Dr. Brett Thombs and McGill graduate student Michelle ...
In a study that included more than 120,000 adults who were treated for trauma, 16 percent of these patients died within 3 years of their injury, compared to an expected population mortality rate of about 6 percent, according to a study in the March 9 issue of JAMA. The researchers also found that trauma patients who were discharged to a skilled nursing facility had a significantly increased risk of death compared with patients discharged home without assistance.
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Information concerning funding and author conflicts of interest disclosed in the original reports of randomized controlled trials is rarely disclosed when these data are combined in meta-analyses, according to an article in the March 9 issue of JAMA.
"Conflicts of interest (COIs) related to the funding of biomedical research by pharmaceutical companies and financial relationships between researchers and pharmaceutical companies have come under increased scrutiny in recent years. COIs may influence the framing of research questions, study design, data analysis, interpretation ...
