The long-term objective of this proposal is the establishment of an International Cooperative Biodiversity Group (ICBG) that would form an interdisciplinary team to discover pharmaceutical agents from poorly understood Costa Rican organisms. The initial group, in this planning phase, is the National Biodiversity Institute (INBio) in Costa Rica and several laboratories, centers, and initiatives at the Harvard Medical School (HMS). The poorly understood organisms are endophytic fungi, the fungi that live inside higher plants, and uncultured microbes from a variety of environments. The primary focus will be endophytic fungi, and these will be field collected, strain selected, fermented, extracted, and pre-fractionated at INBio. The resulting fractions will be submitted to high-throughput screening (HTS) at the Harvard Medical School and the Harvard School of Public Health. The number of screens is exceptionally broad, and the major therapeutic areas explored will be cancer, neurodegenerative diseases, and malaria. The planning phase of the grant will establish technologies and protocols for the planned ICBG. Key technologies are the use of BioXplore to prefractionate natural product extracts and the utility of high-throughput DNA sequencing to establish molecular taxonomy for the poorly understood organisms. The separation technology will be assess both through analysis of HTS screening data and benchmarking the efficiency of purifying compounds from key fractions.
| Santagata, Sandro; Xu, Ya-Ming; Wijeratne, E M Kithsiri et al. (2012) Using the heat-shock response to discover anticancer compounds that target protein homeostasis. ACS Chem Biol 7:340-9 |
