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 functioning.

Other Awards

Michael E. Talkowski, Ph.D.
Mechanistic dissection of three-dimensional regulatory architecture in neurodevelopmental disorders
Among the most intriguing discoveries to emerge from technological advances in recent years are the insights into how the three-dimensional (3D) structure of the genome influences many aspects of local…
Vikaas S. Sohal, Ph.D.
Do dopamine signals promote flexible behavior by recruiting synchronized brain rhythms?
Problems with cognition are the major cause of disability in schizophrenia. One idea is that these result from having too little dopamine in a part of the brain called the…
Xinyu Zhao, Ph.D.
Interrogating Experience-Induced Gene Regulatory Network Dynamics in Interneurons
Understanding the complex relationships between gene expression, neuronal plasticity, and behavior is a fundamental goal of neuroscience. However the brain contains many types of neurons. Therefore, a systematic understanding of…
Ryohei Yasuda, Ph.D.
Imaging dynamics of endogenous protein interactions in single dendritic spines
Changes in the efficiency of synaptic communications between neurons underlie learning and memory. This process is called synaptic plasticity and is caused by biochemical reactions mediated by hundreds of species…