The importance of nuclear position to Emery-Dreifuss Muscular Dystrophy

Project: Research


  • Eric S Folker (PI)


The relationship between cellular structure and function is the key question that has motivated biologists throughout time. One cell type that has been heavily investigated is that of striated muscle. Striated muscle refers to both skeletal muscle and cardiac muscle, and research over the past century has revealed the relationship between the structure of the myofibril and the ability of the muscle cell to produce force. Indeed, this structure-function relationship remains among the best understood in biology. However, much is still not understood regarding the structure-function relationship of the full muscle cell. Many diseases of striated muscle have been linked to genes that encode proteins that have not been identified to contribute to the structure or function of the myofibril. How mutations in these genes impair muscle function is a crucial question for cardiovascular health moving forward. This knowledge will change the way that the specific disease is approached and will impact our general understanding of muscle development and identify novel therapeutic avenues.Emery-Dreifuss Muscular Dystrophy (EDMD) is a disease of striated muscle. It is characterized by the deterioration of the skeletal muscles, but patients suffer mortality from poor function of their cardiac muscles. The coincident effects on both muscle cell types indicates that the underlying cell biology of the disease is conserved between cell types. EDMD-linked genes do not encode proteins of the myofibril, but rather proteins that localize to the nucleus and range from inside the nucleus to the outer membrane of the nucleus.This research will investigate the genetic linkages of the EDMD-linked genes and identify the cellular processes that these genes regulate, and test the hypothesis that their role in nuclear positioning is essential for muscle function. High resolution microscopy combined with quantitative analysis will determine what aspects of cellular organization are affected by each gene and will correlate these effects with muscle function. In total, these experiments will identify underlying cellular pathology associated with EDMD and long-term present processes that can be used as therapeutic targets and biomarkers for therapeutic evaluation.
Award amount$231,000.00
Award date01/01/2015
Program typeScientist Development Grant
Award ID15SDG22460004
Effective start/end date01/01/201512/31/2017