Nancy P. Keller
Professor, Dept. Medical Microbiology & Toxicology; Dept. BacteriologyAddress: 1550 Linden Drive
Phone: (608) 262-9795
Office: 3476 Microbial Sciences Building
The long-term goal of my research program is to reduce aflatoxin and sterigmatocystin contamination of food and feed crops. Aflatoxin (AF) and sterigmatocystin (ST) are toxic and carcinogenic secondary metabolites produced by the same biochemical pathway in several Aspergillus spp. My program focuses on identifying the molecular genetic processes controlling expression of ST/AF biosynthesis and host metabolites which effect fungal growth and ST/AF biosynthesis. Results from these areas of research are directed towards designing rational ST/AF control strategies and should contribute to control of other fungal pathogens.
We are using A. nidulans to dissect the molecular mechanisms governing genetic control of ST biosynthesis. We have isolated a ST gene cluster in A. nidulans and have identified gene functions within the cluster through gene disruption and sequence analysis. This cluster contains 26 genes encoding both enzymatic activities and regulatory proteins necessary for ST and AF biosynthesis. We have demonstrated that both regulatory and structural genes are conserved between the A. nidulans ST gene cluster and the A. flavus and A. parasiticus AF gene clusters. Most interestingly, we find that both sporulation and mycotoxin biosynthesis are inactivated by the same Ga protein-dependent signaling pathway thus suggesting the possibility of a strategy to control inoculum and ST/AF production simultaneously.
We are also interested in host factors which affect the regulation of mycotoxin production in Aspergillus spp. and have identified linoleic acid-derived compounds from the lipoxygenase pathway of plants which regulate both fungal sporulation and ST/AF production. One current goal involves transforming corn and peanut plants with a soybean lipoxygenase gene whose product inhibited AF/ST biosynthesis in laboratory studies. Ultimately, many of our studies should lead to creating transgenic crops where AF/ST-inducing or inhibiting traits will be engineered 'out' or 'into' plants respectively.
These studies will be complemented by functional genomic projects where we are involved in sequencing the Aspergillus genome and analyzing Aspergillus/seed ESTs. Microarray analysis of host seed and Aspergillus genes should reveal those set required for pathogenesis and aflatoxin production in situ.