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 Dr. Eberwine’s 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 the understanding of basic mitochondrial function. In particular Dr. Eberwine’s lab 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

Chaolin Zhang, Ph.D., Columbia University
Human-specific Alternative Splicing, Brain
Development, and Ciliopathies
Like movie frames needing to be edited to tell an engaging story, pieces of genetic information stored in DNA for each gene need to be sliced and rejoined, through a…
Jason Shepherd, Ph.D. University of Utah
Virus-like Intercellular Signaling Underlying Autoimmune Neurological Disorders
Dr. Shepherd’s lab discovered that a brain gene critical for memory and cognition, Arc, has biochemical properties like retroviruses such as HIV. Arc protein can form virus-like protein capsids that…
Yuki Oka, Ph.D., California Institute of Technology
Molecular Mechanisms of Osmolality Sensing in the Mammalian Brain
Animals constantly detect and process sensory signals to react appropriately. External sensory information (e.g., light and sound) serves as prominent environmental cues to guide behavior. On the other hand, our…
Angelique Bordey, Ph.D., Yale University
The Role of Ribosomes in Synaptic Circuit Formation and Socio-Communicative Deficits
Dr. Bordey and her lab’s proposal aims at identifying a molecular mechanism responsible for autism-like socio-communicative defects in the developmental disorder, tuberous sclerosis complex (TSC). TSC is a genetic disorder…