- Michael Smith Laboratories
- Department of Microbiology and Immunology
- Faculty of Land and Food Systems
- Ph.D. (1984) University of Washington
We are interested in several aspects of fungal biology including pathogenesis, morphogenesis, infection-related gene expression, and self versus nonself recognition. The focus of much of our work is on understanding the mechanisms by which fungal pathogens sense and respond to nutrients during proliferation in host tissue. The fungal species that we are studying include the cereal pathogens Ustilago maydis and Ustilago hordei. These basidiomycete fungi are highly amenable to molecular genetic experimentation and cause dramatic diseases on maize and barley, respectively. We are also using the basidiomycete Cryptococcus neoformans as a model to explore fungal pathogenesis. This fungus is an opportunistic pathogen of immunocompromised humans and is believe to be responsible for ~15% of all AIDS-associated deaths. Examples of projects are underway in the laboratory are as follows:
- U. maydis is an excellent model for studying biotrophic interactions between fungi and plants. With support from the Natural Sciences and Engineering Research Council of Canada, we are using molecular genetic and genomic approaches to characterize the response of the fungus to the nutritional signals during the infection of maize tissue.
- We have also characterized the role of the cAMP signal transduction pathway in the control of morphogenesis and pathogenesis for U. maydis and C. neoformans. For U. maydis, we have found that mutants defective in the cAMP pathway are altered in cell shape and virulence. For example, mutants defective in adenylate cyclase or in cAMP dependent protein kinase (PKA) no longer grow by budding and instead display constitutive filamentous growth. In contrast, cells defective in the regulatory subunit of PKA display a multiple budding phenotype. In C. neoformans, the cAMP/PKA pathway is critical for nutrient sensing and the deployment of key virulence factors including melanin and the polysaccharide capsule. With support from the Canadian Institutes for Health Research, we have developed transcriptome and proteome datasets for investigating cAMP/PKA signaling. For both fungi, we are identifying genes encoding downstream targets of PKA and characterizing connections with nutrient sensing and disease.
- A major effort in the laboratory involves the analysis of iron and phosphate sensing by C. neoformans. These nutrients are important for proliferation of the fungus in vertebrate hosts, and they are also signals for the deployment of virulence traits including the polysaccharide capsule. This work is supported by the National Institutes of Health and has led to a mechanistic characterization of iron uptake systems and iron regulators, and an understanding of the roles of these functions during disease.
- What are the mechanisms of fungal pathogenesis?
- How do fungal pathogens deploy virulence factors to attack hosts?
- How do microbes interact in antagonistic and mutually beneficial ways?
- Are there opportunities for novel therapeutics based on mutant screens, microbial products and repurposed drugs?
Biochemistry, biotechnology, biological imaging, genomics, immunology, infectious disease, protein regulation, agriculture, cell delivery, microbial pathogenesis, plant biology, gene editing, metabolomics, food security
To learn more about the Kronstad Lab, please visit kronstadlab.msl.ubc.ca.