A/Professor Paul Ebert
We are using a genetic model organism to study the genetics of longevity as it relates to oxidative stress. Caenorhabditis elegans, a leading model organism for studies of longevity, has a completely sequenced genome and is unsurpassed for genetic analysis. I have selected mutants resistant to a chemical which induces oxidative stress via mitochondrial disruption. These mutants exhibit a dramatic increase in post-reproductive life expectancy. The mutant nematodes are not only being tested for longevity, but also for cross-resistance against a range of oxidative stressors. We are currently engaged in the map-based cloning of the mutated genes and are testing previously characterised stress resistant mutants for a longevity phenotype.
More recently, we have begun a detailed and systematic genetic analysis of mitochondrial function. This project is providing some surprising insight into the roles of specific proteins including a previously unknown communication link between the mitochondria and the nucleus.
Stored grain is protected from insect pests by fumigation with phosphine, a compound which induces oxidative stress. Pest insects that survive exposure to phosphine 240 times the normally lethal level have recently been discovered in Australia. Resistance to this effective, inexpensive and environmentally friendly fumigant has been identified by the Australian grains industry as a national priority issue as there are no equally suitable pest control alternatives. We are investigating the mode of phosphine action and the mechanisms of resistance to allow 1) the effective monitoring of resistance, 2) improvement of fumigation strategies, and 3) the identification of suitable alternatives or synergists. We have identified two genes which together account for high-level phosphine resistance. One of these genes is currently the target of a map-based gene cloning effort. The genetics of additional phosphine resistance outbreaks across Australia and southeast Asia are also being investigated.
This project involves identification of resistance genes by genetic mapping, map-based gene cloning, DNA sequencing, bioinformatics and confirmation of gene function by RNAi. The project also involves toxicology and physiology as part of the search for mechanisms of action and synergistic chemicals. The project benefits from close research ties with the Queensland Department of Primary Industries and the grain industry. As a result of these linkages, students with strong academic backgrounds who wish to participate in the insect projects are eligible to apply for grains industry scholarships. A personal connection to agriculture will enhance your competitiveness for a scholarship.
Schlipalius, D. I., Valmas, N., Tuck, A. G., Jagadeesan, R., Ma, L., Kaur, R., Goldinger, A., Anderson, C., Kuang, J., Zuryn, S., Mau, Y. S., Cheng, Q., Collins, P. J., Nayak, M. K., Schirra, H. J., Hilliard, M. A., and Ebert, P. R. (2012). A core metabolic enzyme mediates resistance to phosphine gas. Science (New York, N.Y.), 338(6108), 807–810.
Mathew, M., Mathew, N., Ebert, P.R. (2012). WormScan: A technique for high-throughput phenotypic analysis of Caenorhabditis elegans. PLoS ONE 7(3): e33483.
Kuang, J., Ebert, P.R. (2012). The failure to extend lifespan via disruption of Complex II is linked to preservation of dynamic control of energy metabolism. Mitochondrion 12: 280-287.