Scientists at the University of Kansas have made major inroads to understanding Matrin-3. ELP3, a little-studied protein, might have a key role in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dr. Meredith Jackrel, pictured above, is the group’s principal investigator as they explore the behavior and molecular makeup of Matrin-3. This understudied RNA-binding protein has the potential to transform health in remarkable ways.
Matrin-3 had a stellar conference debut. Jackrel’s team wanted to create a more detailed portrait of its functions and interactions in cells. One of the biggest obstacles we encountered was the difficulty in chemically purifying Matrin-3. This separation was critical for us to be able to cleverly and efficiently study its properties.
Advances in Purification Techniques
To investigate Matrin-3 more thoroughly, the research team developed a reliable method to purify the protein using advanced techniques in biophysical chemistry. This creative workflow was the key that enabled them to get Matrin-3 out of its cellular environment. Now, they’re able to pursue more targeted research to understand its behavior and properties.
From these experiments, Macy raised the protein purity to new levels and created experimental techniques to advance the study of these small assemblies. Dr. Jackrel emphasized that this work is a particularly significant breakthrough for our lab and critical to understanding the underlying causes of ALS.
The achievement of being able to generate high purity samples of Matrin-3 is considered a major breakthrough in the study of this protein. These highly purified samples should enable subsequent studies to probe Matrin-3’s function in both health and disease.
Insights from Electron Microscopy
Electron microscopy was pivotal in unmasking the 3D structural forms of Matrin-3. The team visualized the protein’s spherical and wormlike assemblies, finding that it can shift form from one to the other. Finding minuscule spheres spontaneously converting into worm-like forms was just the starting point for deeper exploration into the resulting world of ideas.
We discovered these little spheres that just organically appeared to morph into these worm-like structures,” Jackrel said. Scientists think that this change occurs via a process known as microphase separation. Yet, studies in this field have been challenging due to the minuscule scale of these structures.
This discovery indicates that Matrin-3’s capacity to take on various configurations might be key to its role in cellular functions. And how these forms interrelate might shed light on their potential contribution to neurodegenerative diseases.
Implications for ALS Research
Matrin-3’s association with ALS has led investigators to hypothesize that mutations in this protein alter its function in some way. The research team hypothesized that ALS-related mutations might strengthen these worm-shaped proteins. They proposed that this newfound resistance could alter the dynamic, predictable changes that occur as a cell undergoes various processes.
The mutations linked to ALS appear to be causing these worms-shaped proteins to be less rigid and more prone to alterations. Jackrel explained. This natural resistance can ultimately result in the build-up of lethal aggregates. These abnormal aggregates interfere with regular cellular activity and accelerate the development of neurodegenerative disorders.
Jackrel’s lab has developed reproducible purification protocols and imaging modalities. They expect to do more research to understand Matrin-3’s complex roles in normal physiology and disease. Through this exciting ongoing research we hope to better understand the biology of ALS and FTD. It seeks to better pinpoint possible therapeutic targets for treating these conditions.