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Postdoctoral position: Mitochondrial DNA quality control and plant mitochondria engineering (Hay lab)

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. mtDNA mutations also accumulate over time and contribute to a number of diseases of aging including Alzheimer’s, Parkinson’s, and sarcopenia. Reducing heteroplasmy is, therefore, an important therapeutic goal. We have developed systems in which heteroplasmy for a specific lethal mtDNA deletion can be created at will in vivo. We find that mtDNA quality control is normally weak, but can be dramatically enhanced in multiple ways to promote the selective elimination of deletion-bearing mtDNA http://www.nature.com/articles/ncomms13100

 We 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.

 We also seek individuals interested in using related technologies to engineer the plant mitochondrial genome, something that thus far has only been possible in single-celled organisms such as yeast and algae.

Contact:
Professor Bruce Hay
Division of Biology and Biological Engineering
California Institute of Technology
MC 156-29
1200 East California Boulevard
Pasadena, CA 91125
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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