This award supports several research visits by Dr. Vladimir Macko, Boyce Thompson Institute of Cornell University, to the Swiss Federal Institute of Technology in Zurich in order to collaborate with Dr. Duilio Arigoni in studies of the chemistry and biology of host-selective toxins from plant pathogenic fungi. Collaboration with Dr. Arigoni, a world reknowned natural products chemist, will enhance Dr. Macko's long-term domestic research on the mechanism of action of these toxins which is directed at gaining a better understanding of host-pathogen interactions at the molecular level. The specific experimental objectives of their proposed research are: 1) to isolate and characterize the host-selective toxins from the plant pathogenic fungus Periconia circinata (PC); 2) to establish the structure-activity relationship for the PC toxins: and 3) to prepare a radioactively labeled PC toxin that could serve as a probe in future studies of its site of action (receptor) in the host plant. Most of this work will be carried out in the U.S. laboratory. Spectral analysis by various methods will be carried out in both laboratories, and Dr. Arigoni's virtually unique expertise in interpreting spectra of the bioactive compounds will be extremely valuable. Dr. Arigoni will carry out parallel research on the chemical and biological synthesis of the active compounds and their precursors, with concomitant exchange of samples, ideas and information with Dr. Macko. Despite the contributions of modern, quantitative biology to advances in the analysis of the physiology and biochemistry of host-pathogen interactions, we lack a basic understanding of specificity in toxins and the molecular mechanisms of resistance and susceptibility. The elucidation of the molecular basis of specificity in host-pathogen interactions is one of the most important objectives in contemporary plant pathology, because it will help in identifying and manipulating the disease reaction genes and their products. There is also increasing interest in bioactive natural products because of their potential applications in agriculture and biotechnology.
