AP3 This associate program of PMS-ICBG will characterize the chemical diversity inherent in mollusk symbiotic bacteria. We have demonstrated that mollusks contain diverse symbiotic bacteria, including strains that are closely related to previously identified strains, but also very commonly to rare or unique types of strains that have otherwise resisted cultivation and that are not available in other culture collections. We have demonstrated that these strains provide a rich, privileged source of novel, biologically active natural products with potential in treating human diseases. The goal of this program is to isolate and purify biologically active components from these bacteria. In addition, we will determine which types of compounds are important to symbiosis, and we will follow up on potential pharmaceutical hits by discovering or synthesizing active analogs in a drug development strategy. Another critical aspect of AP3 is training. Our goal is to help MSI-UP become a globally known center for natural products chemistry. With the recent acquisition of chemical infrastructure, such as the first modern NMR and MS instrumentation in the country, and an excellent educational environment, MSI-UP is poised to make this leap, which will be greatly facilitated through carefully planned interactions in this PMS-ICBG. To achieve these goals, we plan to: 1) Prioritize bacterial samples for chemical and biological analysis; 2) Elucidate structures; 3) Provide training to aid the development of natural products chemistry at MSI-UP; 4) Optimize hits via chemical approaches.