DNA Precursor Metabolism in Mitochondria: Simulations of Anti-viral Drug Toxicity & Genetic Diseases

Mitochondria play a central role in ATP production, apoptosis control, and numerous other biochemical processes. As a vestige of their bacterial ancestors, mitochondria still contain a small genome encoding 13 proteins necessary for the function of the electron transfer chain, which generates the vast majority of the ATP used by the cell. The mutation or loss of these small DNA molecules is fatal to almost all eukaryotic cells. An individual mitochondrial DNA (mtDNA) molecule only survives for about two weeks. Contrast this to the nuclear DNA molecules which can survive for a century or more. Due to this short lifespan, the mtDNA in all cells must be continually copied to maintain a sufficient population of mtDNA. Our research group is developing computational models of the metabolism of the deoxyribonucleotides needed for mtDNA replication. In one project we are applying this model to a group of genetic diseases that affect the enzymes of this metabolism. In another project, we are investigating the toxic effects of nucleoside analog drugs on this metabolism. These drugs, such as AZT, are the primary treatment for HIV/AIDS. Toxicity of these drugs, due to damage to the patients' mitochondria, is a serious problem with maintaining AIDS therapy.

David Samuels, PhD

David Samuels is an assistant professor at the Virginia Bioinformatics Institute at Virginia Tech, where his group works on computational biomedical research, mainly in the area of mitochondrial medicine. Dr. Samuels' PhD is in Physics, from the University of Oregon. He was a postdoctoral fellow at Stanford, NASA, and at Emory University. Later, he was Reader in Applied Mathematics at the University of Newcastle upon Tyne in the UK. At Newcastle, David began to work with members of the Neurology department in the medical school. In 2002 David moved to the new bioinformatics research institute at Virginia Tech to devote his research to biomedical work, in collaboration with several clinical and lab researchers.