University of Missouri-Kansas City, Spencer Building, 5009 Rockhill Rd., Kansas City, MO 64110
Our Research (for non-scientists)
Why do we study muscles, and what is alternative splicing?
We rely on our muscles for simple movements, from picking up a pencil to walking across a room. Muscles also enable unconscious movements, such as beating of the heart, the digestive action of the stomach or breathing. Muscles are able to facilitate movement because they contract, meaning they are able to shorten and reextend. This contraction ability is powered by mini-motors called sarcomeres.
We have hundreds of muscles in our bodies with different functions and distinct contractile properties. To achieve this, muscles modify their sarcomeres to adapt to physical demand. For example, the heart needs to be very stiff to properly pump blood, while muscles in the legs are more flexible to permit walking. In addition to regulating which proteins are present to build their sarcomeres, muscles also produce different versions of the same protein, termed isoforms, using a process called alternative splicing. Alternative splicing generates multiple versions of the same protein that for example can be more or less stiff or interact more strongly or weakly with other proteins, ultimately helping define specific contractile properties for different muscle types.
There are many regulators that help a muscle select which proteins and protein isoforms it will produce. Misregulation or loss of regulators responsible for alternative splicing causes muscle diseases such as myotonic dystrophy and dilated cardiomyopathy, along with many others. These disorders cause muscles to produce the wrong protein isoforms, for example a version of the protein normally found in leg muscle can be found in heart. Patients with these disorders experience a loss of muscle and impaired muscle function, dramatically decreasing their quality of life and life expectancy. The goal of our research is to understand how regulators of alternative splicing work in muscle, and what goes wrong in muscle disease. A better understanding of how muscles develop normally and what is disrupted in disease will aid in developing new treatments for these debilitating disorders.
Dr. Spletter's 2018
TEDxTUM talk
Curious? Motivated to learn more? Check out this animated and easy-to-understand presentation on YouTube.