ENDOPHYTES & ALKALOIDS--CHEMISTRY/GENTICS/BIOLOGIC ACTIV

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Description (Adapted from Application): Mycotoxins are fungal secondary metabolites that are toxic to animals and humans. Fungi that live inside plant tissues (endophytes) produce some of the most toxic and interesting mycotoxins. This project will study an unexplored group of endophytes of grasses and lupins, their toxins, and the biological activity and pharmaceutical potential of the toxins. Many grasses contain endophytic fungi (family Clavicipitaceae). The fungi produce alkaloids of great importance to man: they protect the plant host from herbivory, they cause enormous losses to the livestock industry, and they are useful as drugs. They are also interesting models to study relationships between pathogenicity and mutualism. Although grass endophytes have been studied extensively in temperate areas, almost nothing is known about them in the Neotropics. Lupins from the same areas will be tested for presence of the endophyte Phomopsis and phomopsins. Phomopsins are tubulin-binding mycotoxins that cause diseases in animals, and, possibly in humans. Study of tropical endophytes of grasses should provide new alkaloids of biochemical and pharmacological interest, new insights into animal health problems, and a new context to test ideas of host-pathogen relationships developed in temperate systems. This project has four interrelated parts: 1) isolation of grass endophytes in the Neotropics, which will also provide materials for the other parts; 2) DNA fingerprinting and sequencing study of some endophytes, to test hypotheses about evolution and hybridization of the group and to decide which fungi are most likely to produce novel alkaloids; 3) identification of alkaloids and phomopsins; and 4) studies of biological activity and pharmaceutical potential of the compounds, based on insect feeding bioassays, an in vitro bioassay for estrogenicity, and a spore germination bioassay to test for inhibition of mitosis.