Postdoctoral Fellow at Caltech: Mitochondrial DNA quality control and animal and plant mtDNA engineering
Job Description
Mitochondrial DNA (mtDNA) encodes RNAs and proteins required for oxidative phosphorylation, the primary method of ATP production in nucleated cells. mtDNA often exists in a state of heteroplasmy, in which deleterious mutant mtDNA co-exists in cells along with wildtype mtDNA. Heteroplasmy for pathogenic mutations is common, and high frequencies of mutant mtDNA result in severe maternally inherited syndromes. Inherited and somatically acquired mutations also accumulate over time and contribute to a number of diseases of aging including Alzheimer's, Parkinson's an age-related muscle loss and frailty (sarcopenia). Reducing heteroplasmy is therefore an important therapeutic goal. We have developed a system in which heteroplasmy for a specific lethal mtDNA deletion can be created at will in vivo in Drosophila. Using this system we found that mtDNA quality control is normally weak, but can be dramatically enhanced in multiple ways to promote the selective elimination of deletion-bearing mtDNA. (Kandul, N.P., Zhang, T., *Hay, B.A. and *Guo M. (2016). Selective removal of deletion-bearing mitochondrial DNA in heteroplasmic Drosophila. Nature Communications. http://www.nature.com/articles/ncomms13100We seek highly motivated individuals who are interested in using this system, and/or related systems in mammalian cells, to understand the basis for mtDNA quality control, and how to stimulate it, in somatic cells and in the germline. Genetic and drug-based screens are of interest, as are experiments focused on the cell biology of mtDNA quality control and the basis for the preferential amplification of mutant genomes often observed in vivo.
Finally, we also have an interest in using related technologies to engineer the mitochondrial genome, something that thus far has only been possible in single-celled organisms.
Contact:
Bruce A. Hay
Professor
Division of Biology and Biological Engineering
California Institute of Technology
MC156-29
1200 East California Boulevard
Pasadena, CA 91125
haybruce@caltech.edu
http://www.bbe.caltech.edu/content/bruce-hay
A CV, a summary of research background and interests, and letters of reference should be sent to haybruce@caltech.edu in PDF format.
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