Fungi have both beneficial and harmful impacts on human affairs. They are essential for decomposition and nutrient cycling, as plant and animal symbionts, and for industrial fermentation processes. Fungi also represent a major group of plant and animal pathogens, and cause food and materials spoilage and human allergies. I am interested in developing control strategies that selectively inhibit target fungal species.
Research in my laboratory is carried out in four general areas and selected publications within each area are provided under the “publications” heading of this blog.
First, we are characterizing genes involved in fungal nonself recognition and exploring how the products of these genes are integrated into cellular pathways. This is fundamental research since, as with other life forms, fungal individuals must constantly detect and appropriately respond to contacts with other members of their community. The nonself recognition process is essential for acquiring and maintaining resources, mating, and reducing the spread of invasive genetic elements such as plasmids transposons and viruses. In addition to exploring how nonself recognition systems may be used to control fungal growth processes, we are gaining insights into the complexity of nonself recognition systems as a basic attribute of life.
Second, we look for and characterize compounds that inhibit the growth of microbes. For example, plant-derived chemicals represent an ideal source of new antifungals – since fungi encompass major plant pathogens and plants are unable to “run away” from such pathogens, plants have evolved a vast array of antifungal compounds. We use ethnobotanical and ecological approaches to identify candidate plants, extract bioactive compounds from these plants, and use bioassay-guided fractionation and analytical chemistry to identify naturally-occurring antifungals. Recently we have broadened our search for antibiotics by screening secondary metabolites of various microbes, including mushrooms and synthetic analogs of existing inhibitors. We are also developing bacterial control strategies based on naturally occurring bacteriophage.
In addition to discovery, it is important to understand the mode of action of antimicrobials. Ideally, a new antibiotic should have a different inhibitory mechanism than existing ones. Also, priority should be given to developing antimicrobials that act specifically on the target organism. For example, the fungal cell wall is a unique attribute of fungi, one that sets fungi apart from their sister group, the animals. For mode of action studies of antifungals and antibacterials we initially use gene deletion arrays (GDAs) of yeast and E. coli, respectively. Genetic inferences gained from GDAs are subsequently tested by secondary assays.
Finally, we pursue studies of general genetics in my laboratory. For example, we are interested in the theory and practice of developing high-resolution genetic markers for population genetics applications, strain typing and molecular ecology. Additional examples of genetic and biological studies on fungi and insects from my laboratory can be found under the “publications” heading of this website.