Molecular Studies of Agriculturally and Medically Important Fungi Our research group is investigating genetic regulatory mechanisms that control the beneficial as well as the detrimental impact of fungal species that are of agricultural and medical importance. Fungi produce a wide range of natural products (also denominated secondary metabolites); among them are antibiotics, anti-tumoral drugs, cholesterol reducing drugs and carcinogenic mycotoxins. The biosynthesis of these compounds is often found to be genetically linked to morphogenesis, including the formation of air-borne spores, formation of fruiting bodies or of resistant structures that allow these eukaryotic organisms to survive adverse environmental conditions.
One of the major interests of my group resides on the identification of regulatory elements governing the biosynthesis of mycotoxins and morphological development in two fungal genera, Aspergillus and Fusarium. Contamination of the world’s crops (corn, peanut, cotton, sorghum, tree nuts, etc.) by mycotoxins produced by these fungi costs billions of dollars annually and constitutes an important health threat. Current control strategies fail to effectively eliminate mycotoxin contamination. It continues to be a major economic problem in the U.S. and a serious health threat in developing countries. Our work focuses on the discovery of new genetic elements regulating secondary metabolism and morphogenesis, or both, that will contribute to a better understanding of these signaling pathways and to the establishment of strategies to control fungal dissemination, survivability and/or mycotoxin contamination. Among others, we study a novel regulatory system, called velvet (VeA), unique to fungi, with high potential to control plant diseases in Aspergillus and Fusarium spp. We have demonstrated that velvet is vital for the production of aflatoxin, cyclopiazonic acid and aflatrem mycotoxins by Aspergillus flavus. We also showed that VeA is indispensable for the production of sclerotia, resistant structures formed by A. flavus. Our group, in collaboration with the USDA, has carried out functional genomic studies to elucidate down-stream regulatory pathways controlling toxin production, sporogenesis and formation of sclerotia in A. flavus. Based on our studies, the role of the veA gene as a regulator of in morphogenesis and secondary metabolism appear to be conserved in Aspergilli and other fungal genera.
Rocio Duran, Ph.D. Candidate
Sourabh Dhingra, Ph.D. Candidate
Leeanne Szersen, M.S. Student
Jennifer Rohrssen, M.S. Student
Due to the conservation in many aspects of the genetic regulatory network across different fungal species, some of these global regulatory genes also have a high potential as targets for human and animal disease control. We are also interested in the medical application of our research. In my laboratory we are studying regulatory genes controlling morphogenesis and secondary metabolism in Aspergillus fumigatus and Histoplasma capsulatum. Both fungi are opportunistic human pathogens capable of causing disease in immuno-depressed patients. The increasing numbers of patients with hematological malignancies, AIDS, patients undergoing chemotherapy or organ transplants are highly susceptible for aspergillosis and histoplasmosis. Our studies contribute to open new avenues for future detection and treatments of these diseases and other recalcitrant fungal infections.
Our research benefits from using a well established model system for molecular and genetic studies, Aspergillus nidulans. This filamentous fungus is one of the most characterized of eukaryotic organisms. This model system is especially productive in the study of secondary metabolism gene clusters and developmental genes, as well as the signal transduction pathways governing these processes. For example, using this phylogenetically related model organism our laboratory has demonstrated that the unique-to-fungi velvet regulator is carried into the nucleus by an importin alpha carrier, where it forms a protein complex. In this nuclear velvet complex VeA binds to light-sensing proteins, putative methyl transferases postulated to be involved in chromatin modification and transcription factors. We hypothesize that the VeA protein is essential for the integration of external stimuli (for example light) with a genetic nuclear response that leads to morphological and chemical adaptation of this organism to its environment. We are studying the architecture and dynamics of this protein complex.
While we are trying to reduce the detrimental effects of fungi, we are also trying to enhance those effects that are beneficial, for example the biosynthesis of medical drugs. Using A. nidulans as a model, we are trying to elucidate regulatory mechanisms susceptible to modification that could improve production of compounds of biomedical importance.
A list of recent published work from our group can be viewed at http://www.bios.niu.edu/calvo/calvo.shtml.