Forum for Science, Industry and Business

Scientists pioneer microscopy technique that yields fresh data on muscular dystrophy

Scientists at USC have developed a new microscopy technology that allows them to view single molecules in living animals at higher-than-ever resolution.

A new single-molecule imaging technique developed at USC provides new insights into the role of dystrophin proteins for muscle function in Caenorhabditis elegans worm models of Duchenne muscular dystrophy.

Credit: Courtesy of Fabien Pinaud

Dubbed "Complementation Activated Light Microscopy" (CALM), the new technology allows imaging resolutions that are an order of magnitude finer than conventional optical microscopy, providing new insights into the behavior of biomolecules at the nanometer scale.

In a paper published on Sept. 18 by Nature Communications, the researchers behind CALM used it to study dystrophin – a key structural protein of muscle cells – in Caenorhabditis elegans worms used to model Duchenne muscular dystrophy.

Duchenne muscular dystrophy is the most severe and most common form of the degenerative disease.

The researchers showed that dystrophin was responsible for regulating tiny molecular fluctuations in calcium channels while muscles are in use. The discovery suggests that a lack of functional dystrophin alters the dynamics of ion channels – helping to cause the defective mechanical responses and the calcium imbalance that impair normal muscle activity in patients with muscular dystrophy.

Ten Times the Precision of Optical Microscopy

CALM works by splitting a green fluorescent protein from a jellyfish into two fragments that fit together like puzzle pieces. One fragment is engineered to be expressed in an animal test subject while the other fragment is injected into the animal's circulatory system.

When they meet, the fragments unite and start emitting fluorescent light that can be detected with incredible accuracy, offering imaging precisions of around 20 nanometers. Conventional optical microscopy of living tissues can only achieve a 200 nanometer resolution at best. For scale, a sheet of paper is 100,000 nanometers thick.

"Now, for the first time, we can explore the basic principles of homeostatic controls and the molecular basis of diseases at the nanometer scale directly in intact animal models," said Fabien Pinaud, assistant professor at the USC Dornsife College of Letters, Arts and Sciences and lead researcher on the project.

Pinaud collaborated with scientists from the University Claude Bernard Lyon in France and the University of Würzburg in Germany.

Building the Tools for Tomorrow's Research

The new technology lies at the heart of the convergence of science and engineering at USC, where researchers from both fields collaborate to create the tools that make scientific and medical breakthroughs possible.

"There are trillions of proteins at work on an infinitely small scale at every moment in an animal's body. The ability to detect individual protein copies in their native tissue environment allows us to reveal their functional organization and their nanoscale molecular behaviors despite this astronomical complexity," Pinaud said.

Next, Pinaud and his colleagues will focus on engineering other colors of split-fluorescent proteins to image the dynamics of individual ion channels at neuromuscular synapses within live worms.

"It so happens that the same calcium channels we studied in muscles also associate with nanometer-sized membrane domains at synapses where they modulate neuronal transmissions in both normal and disease conditions," Pinaud said. Using multi-color CALM, his team and collaborators will probe how these tiny active zones of neurons are assembled and how they influence the function of calcium channels during neuron activation.

This research was funded by USC startup funds and the computational work was supported by the USC Center for High-Performance Computing and Communications.

Robert Perkins | Eurek Alert!

Im Focus: Fraunhofer IDMT demonstrates its method for acoustic quality inspection at »Sensor+Test 2019« in Nürnberg

From June 25th to 27th 2019, the Fraunhofer Institute for Digital Media Technology IDMT in Ilmenau (Germany) will be presenting a new solution for acoustic quality inspection allowing contact-free, non-destructive testing of manufactured parts and components. The method which has reached Technology Readiness Level 6 already, is currently being successfully tested in practical use together with a number of industrial partners.

Reducing machine downtime, manufacturing defects, and excessive scrap

Im Focus: Successfully Tested in Praxis: Bidirectional Sensor Technology Optimizes Laser Material Deposition

The quality of additively manufactured components depends not only on the manufacturing process, but also on the inline process control. The process control ensures a reliable coating process because it detects deviations from the target geometry immediately. At LASER World of PHOTONICS 2019, the Fraunhofer Institute for Laser Technology ILT will be demonstrating how well bi-directional sensor technology can already be used for Laser Material Deposition (LMD) in combination with commercial optics at booth A2.431.

Fraunhofer ILT has been developing optical sensor technology specifically for production measurement technology for around 10 years. In particular, its »bd-1«...

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...