Illuminating the invisible: Bringing the smallest protein clusters into focus
Penn engineers are opening new avenues for detecting the proteins implicated in diseases like Alzheimer’s and testing new treatments.
Penn engineers have pioneered a new way to visualize the smallest protein clusters, skirting the physical limitations of light-powered microscopes and opening new avenues for detecting the proteins implicated in diseases like Alzheimer’s and testing new treatments.
White spots represent tiny clusters of proteins detected by CluMPS.
(Image: Thomas Mumford)
In a paper in Cell Systems, Lukasz Bugaj, assistant professor in bioengineering in the School of Engineering and Applied Science, describes the creation of CluMPS, or Clusters Magnified by Phase Separation, a molecular tool that activates by forming conspicuous blobs in the presence of target protein clusters as small as just a few nanometers. In essence, CluMPS functions like an on/off switch that responds to the presence of clusters of the protein it is programmed to detect.
Normally, says Bugaj, detecting such clusters requires laborious techniques. “With CluMPS, you don’t need anything beyond the standard lab microscope.” The tool fuses with the target protein to form condensates orders of magnitude larger than the protein clusters themselves that resemble the colorful blobs in a lava lamp. “We think the simplicity of the approach is one of its main benefits,” says Bugaj. “You don’t need specialized skills or equipment to quickly see whether there are small clusters in your cells.”
For treating diseases like Alzheimer’s, ALS and even cancer, being able to detect protein clusters this small promises to be a foundational advancement, allowing researchers to determine whether or not drugs actually eliminate disease-causing clusters of a target protein in a cell.
“You need a very clear signal,” says Bugaj, to know whether or not a treatment worked. “It’s very obvious when you have a gigantic cluster, but if you have small clusters, it is much harder. Now we can amplify that signal and see which drugs actually dissolve the clusters.”
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