Engineering a Minimal Competency Machinery for Mitochondria
Abstract
This proposal addresses the Fiscal Year 2016 Peer Reviewed Medical Research Program Topic Area "Mitochondrial Disease." Mitochondria are compartments within our cells that utilize nutrients and oxygen to produce energy. Our mitochondria contain their own DNA, and mutations in mitochondrial DNA cause problems in energy production, leading to severe and untreatable disease in humans. A critical issue in studying mitochondrial disease is the lack of appropriate animal models that mimic the symptoms in humans. This is primarily due to our inability to introduce mutations in the mitochondrial genome. We propose here to solve this problem by engineering a strategy to deliver engineered DNA molecules into the mitochondrion, which can then be used as templates to create mutations. In particular, we will use bacteria as a model. Bacteria, which are similar to mitochondria in structure, have evolved sophisticated machinery to import DNA from the outside world, and modify their own genomes. By engineering the bacterial machinery so that it can be used by mitochondria, we will develop methods to program mutations into the mitochondrial genome. Ultimately, if we can use this method to create accurate mice models of human mitochondrial disease, we can begin to develop and test treatments that will benefit patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710140
Entities
People
- Prashant Mishra
Organizations
- United States Army
- University of Texas Southwestern Medical Center