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

Angelique Bordey, Ph.D., Yale University
The Role of Ribosomes in Synaptic Circuit Formation and Socio-Communicative Deficits
Our 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 with a 30-60% incidence…
Adam E. Cohen, Ph.D., Harvard University
To spike or not to spike? Mapping dendritic computations in vivo.
The brain is made of neurons, and neurons convert synaptic inputs to spiking outputs. How does a neuron decide when to spike?
Gina Turrigiano, Ph.D., Brandeis University
Homeostatic Maintenance of Neocortical Excitation-inhibition Balance by Ciliary Neuropeptidergic Signaling
Brain circuit wiring is adjusted during adolescence to generate fully functional circuits, and this process depends on an interaction between genetics and experience. During this period of experience-dependent development, excitatory…
Gregory Scherrer, Ph.D., The University of North Carolina at Chapel Hill
Mechanisms of Affective States and Drug Discovery at the Intersection of Chronic Pain and Opioid Addiction
Pain is normally a sensation that we experience when our body is exposed to damaging stimuli, such as the noxious heat of an open flame. However, when chronic, pain becomes…