RPI researchers seek answers in muscle physiology

Dr. Swank works to uncover the important fundamental details of muscle and the heart

RESEARCHERS ANALYZE a Drosphila to test the fiber’s ability to generate force.

In the Center for Biotechnology and Interdisciplinary Sciences, Dr. Douglas Swank is working on uncovering important fundamental details about muscle and the heart. As a part of the Biology Department for nine years, Dr. Swank has been an integral part of research at RPI. His interest in muscle physiology and disease began in high school and was solidified by a summer undergraduate internship at State University of New York at Buffalo which eventually led to his graduate school study. Dr. Swank has undertaken research projects that may help scientists understand the fundamental importance of several characteristics of muscles and the heart. With the award of two new grants from the National Institutes of Health, new research opportunities have opened up for the Swank laboratory.

A main research project in the lab focuses on heart muscle and point mutations that can be fatal in humans. Over 200 point mutations exist that cause enlargement and extra muscle mass in the heart, which can lead to cardiac arrest. According to Dr. Swank, these point mutations can be difficult to diagnose and are often inherited, as the heart can typically compensate for the reduced area in the ventricles when younger and sometimes allows people with the mutation to live into their 30s and 40s. However, more severe forms of the disease often strike athletes in their teens or 20s, resulting in sudden cardiac arrest. Dr. Swank has partnered with researchers at San Diego State University and Johns Hopkins University to research the mutations that change important muscle proteins which lead to this disease. After modifying the protein genes in flies, Dr. Swank and his team removed a mutated muscle fiber from drosophila, or fruit fly, muscle and test it to determine the fiber’s ability to generate force, and power, as well as the shortening velocity of the fiber. After many trials, they then use this data to establish what specific point mutations do to the muscle fiber and why it causes enlargement of the heart.

Another area of research includes the study of stretch activation in the heart that Dr. Swank has headed for four years. Stretch activation is the process by which the heart muscles are stretched by incoming blood and causes the contraction of the heart to have a much larger force than if the muscle was not stretched. This increases heart muscle power, generation, and efficiency. The stretch activation phenomenon is not understood by the scientific community and the Swank lab’s research could be incredibly important in helping scientists understand more about how this heart mechanism operates.

In the lab, graduate students work on studying many different facets of muscle fiber and heart physiology. Research into the role of different muscle fiber types will increase our understanding of how myosin, the molecular motor that powers muscle contraction, converts chemical energy into force and motion. Using custom-built muscle mechanics apparatuses, the Swank lab measures the tension, force, and shortening velocity that individual muscle fibers produce when expressing different myosin isoforms. This data is used to understand how myosin is forms contribute to setting the mechanical properties of different muscle types, including heart muscle.

In Dr. Swank’s lab, new information is found fairly frequently as the researchers make many small, incremental gains. Dr. Swank believes that the projects done in his lab are small, but important steps in making a whole picture that would allow understanding of the process in question. He hopes that his research can be used to gain insight into diseases and to be applicable to patients with the specific mutations he is researching. However, with such a large number of mutations that he has yet to investigate, one of Dr. Swank’s goals of his current research is to understand generally how the diseases work and why exactly these point mutations cause the disease so that, someday, they can be treated. Still, Dr. Swank is optimistic and notes, “The real breakthroughs in science most often come from basic research. You learn something no one knew before. We are always very much interested in increasing our fundamental understanding of muscle and heart physiology. That’s where you’re most likely to get the real breakthroughs that will lead to big jumps instead of the typical incremental ones.”