Single Mitochondrion Analysis and Engineering for Human Neurological Disease

2017 Scientific Innovations Award
James Eberwine, Ph.D.
Systems Pharmacology and Translational Therapeutics
University of Pennsylvania Perelman School of Medicine

The goal of this proposal is to enable new therapeutic modalities for treating mitochondrial diseases through the development and use of novel mitochondrial engineering procedures. While mammalian genome engineering has been performed for decades, advances in mitochondria engineering have been hindered because little is known about individual mitochondrial differences and it hasn’t been possible to easily insert or delete genes into the mitochondria to assess potential biological roles of these differences. Even if modification were possible, there are hundreds of mitochondria in a cell, making it difficult to envision how to modify all mitochondria in the same way. This application details novel approaches to overcome these issues, providing a technical and theoretical framework to create therapeutic mitochondria and enhance our understanding of basic mitochondrial function. In particular we will detect, quantify and functionally assess specific single mitochondrion mutations in mouse and human neurons and astrocytes, in hopes that these data will provide new insights into the increasingly complex role mitochondria play in modulating neuronal cell functionin.