2011 MDF Research Fellows

John Cleary, PhD
University of Florida, Gainesville, Florida, US

Working with Dr. Laura Ranum, Dr. Cleary's research is titled, “An Investigation of the Genetic Mechanisms in Myotonic Dystrophy" The primary cause of the disease is a mutated version of a gene that contains an excess number of small repetitive sections of DNA. These sections, termed trinucleotide repeats, normally occur in numbers between 5 and 34 but in the mutant version expand upwards to several hundred or even several thousand. As a consequence when transcribed into RNA, the initial step towards making a protein, the repeats, due to their expanded size, soak up cellular proteins that bind repeat-containing RNA creating an RNA gain-of-function effect. Unable to let go of the expanded RNA, these cellular proteins are prevented from accomplishing their regular function and cause a cascade of negative consequences to the cell.

The majority of current research has assumed that certain classes of repeats, due to their location in the gene, are not made into proteins. However recent evidence by the Ranum lab suggests these repeats may actually express a variety of proteins that due to their repetitive nature could have serious cellular consequences. What is perhaps more unexpected is that the repeats make these proteins by essentially taking it upon themselves to start the process - bypassing the cell’s traditional methods by which RNA is made into proteins. These data suggest that in addition to the RNA gain-of-function effects, the expression and accumulation of these unexpected expansion proteins could also contribute to myotonic dystrophy. The focus of Dr. Cleary's postdoctoral research will be to understand the potential role that these proteins play in disease.

Alexa Dickson, PhD
Colorado State University, Ft. Collins, Colorado, US

Working with Dr. Carol Wilusz, Dr. Dickson's research is titled, “The Role of mRNA Stability in Myotonic Dystrophy" Myotonic dystrophy is a genetic disorder caused by an increase of repeats in the DNA. Although the mechanism is unclear, researchers know the increased DNA repeat length causes a defect in CUGBP1, a protein responsible for determining the levels of gene expression in the cell. Without proper control of gene expression, abnormal levels of proteins result, which is thought to cause some of the symptoms in myotonic dystrophy. Dr. Dickson’s proposal examines the role of CUGBP1 in normal cellular function and seeks to determine the defect of the protein in myotonic dystrophy. With this knowledge, researchers may be able to more rationally design therapeutics targeted to improving the quality of life of a myotonic dystrophy patient.