Mitochondrial medicine is an emerging area of research. This field has rapidly developed following the description in the late 1980s of the first mitochondrial mutations that led to human disease. However, through the late 1990s, in vivo animal models were extremely rare and limited to characterizations of spontaneous mutations.
My interests relate to the technical hurdles associated with creating transmitochondrial research animals; i.e., animals harboring engineered mutations in the mitochondrial genome. Though the mitochondrial genome is small (16.6kb in vertebrates), transfection of mitochondrial DNA (mtDNA) or entire mitochondrial genomes into mitochondria is not possible by conventional transgenesis. Furthermore, recombination within mitochondria is a rare event, such that harnessing the mitochondrial recombination machinery is not possible.
To address these issues, our laboratory has utilized a mtDNA large-scale deletion mutation that is small enough to electroporate into isolated mouse mitochondria without causing irreparable damage to the mitochondrial membranes. These transfected mitochondria can then be microinjected into fertilized eggs for production of heteroplasmic mice (mice harboring both wild type and mutated mtDNA) that may serve as an animal model for a similar class of large-scale deletions seen in human patients.
A related project seeks to explore new strategies for introducing isolated, genetically manipulated mitochondria into embryonic stem cells via liposome encapsulation and subsequent fusion of liposome vesicles with the ES cell plasma membrane. Going forward, development of strategies for increasing mtDNA recombination frequency would enable techniques for introducing specific point mutations, allowing for the creation of mouse models for a variety of human diseases of the mtDNA.
In addition to my own research, interactive studies in animal transgenesis through the Auburn University Transgenic Facility are envisioned across a broad spectrum of interests in the life sciences at
. Auburn University