Looking for new gene functions that aid in recovery from nutrient depletion.

Staff Scientist at Washington University School of Medicine.

Zinc metabolism and homeostasis are fundamental biological processes, since zinc is necessary for the function of many proteins and zinc modulates signal transduction pathways. Zinc is an essential nutrient that profoundly affects human health, as zinc deficiency and excess result in a broad spectrum of pathologies. Yet, the mechanisms that regulate zinc metabolism remain poorly defined. In particular, little is known about mechanisms that influence resistance and sensitivity to high levels of zinc. C. elegans is an outstanding experimental system for forward genetics, reverse genetics, and molecular analysis supported by a fully sequenced genome. The identification and characterization of new genes involved in zinc metabolism is a high priority, since this will contribute to a comprehensive understanding of zinc biology and may have practical implications for treating medical problems associated with zinc abnormalities. To identify new genes in zinc metabolism, the Kornfeld laboratory conducted a forward genetic screen with chemical mutagenesis. 19 mutants demonstrated resistance to the toxicity caused by excess zinc. I positionally cloned four of these mutant alleles using a variety of genetic and molecular techniques including whole genome sequencing. This work led to a publication in PLoS Genetics, other work is unpublished and ongoing.