Discipline: Biological Sciences
Subcategory: Physiology and Health
Gregory Herrera Rios - California State University, Los Angeles
Myotonic dystrophy (DM) is a multisystemic genetic disorder that leads to skeletal muscle, cardiac and neurological impairment. DM is characterized by multiple CUG repeats along the DMPK gene, with the severity of the disease increasing with the number of repeats. DM patients exhibit extended muscle contractions due to misregulated ion channels. As a result, normal ion balance, notably calcium, is disrupted leading to cellular damage and eventual death. While research has been aimed at identifying how the CUG repeats regulate gene expression, little is known regarding the effects of DM on organelle function. This study works to understand how DM affects calcium handling between the mitochondria and smooth endoplasmic reticulum to cause extended muscle contractions. An in vitro model of DM will be created by transfecting C2C12 cells with a plasmid containing 950 CUG repeats. This will allow for testing of overall calcium distribution and organelle functions in the control versus diseased state. We will run a mixture of fluorescent microscopy experiments to evaluate calcium distribution and organelle structure, as well as biochemical and functional assays to assess the difference in organelle function between these two groups. I hypothesize that DM cells will exhibit a misregulation of calcium handling leading to calcium overload in the mitochondria, thereby decreasing mitochondrial function. Results should indicate calcium mishandling and inhibited ATP production as shown by the results of the various assays. Therefore, if results should hold to be true, DM will indeed induce calcium mishandling through misregulation of calcium handling protein channels and a decrease in ATP synthesis due to mitochondrial dysfunction. Currently, there are limited DM treatments available and the identification of a new possible cell target may lead to the development of new pharmacological agents to combat the disease.
1. Rau F, et al: Misregulation of miR-1 processing is associated with heart defects in myotonic dystrophy. Nature Struct Biol 2011, 1:1-5
2. Gatchel JR, Zoghbi, H: Diseases of unstable repeat expansion: Mechanisms and Common Principles. Nature Rev Gen 2005, 6:743-753
Funder Acknowledgement(s): Katrina Yamazaki
Faculty Advisor: Katrina Yamazaki, firstname.lastname@example.org
Role: All research will be conducted by the primary artists.