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.
AP3 This associate program of the PMS-ICBG will provide extracts and purified compounds for analysis in our AP2 Symbiosis and AP4 Pharmacology programs. In turn, these compounds will be screened for their pharmaceutical potential in treating human health conditions that include, but are not limited to: neurological conditions, cancers, including pancreatic cancer and glioblastoma, pandrug-resistant bacterial infections, and infections by apicomplexan parasites.
|Barghi, Neda; Concepcion, Gisela P; Olivera, Baldomero M et al. (2015) Comparison of the Venom Peptides and Their Expression in Closely Related Conus Species: Insights into Adaptive Post-speciation Evolution of Conus Exogenomes. Genome Biol Evol 7:1797-814|
|Neves, Jorge L B; Lin, Zhenjian; Imperial, Julita S et al. (2015) Small Molecules in the Cone Snail Arsenal. Org Lett 17:4933-5|
|Cragg, Simon M; Beckham, Gregg T; Bruce, Neil C et al. (2015) Lignocellulose degradation mechanisms across the Tree of Life. Curr Opin Chem Biol 29:108-19|
|Barghi, Neda; Concepcion, Gisela P; Olivera, Baldomero M et al. (2015) High conopeptide diversity in Conus tribblei revealed through analysis of venom duct transcriptome using two high-throughput sequencing platforms. Mar Biotechnol (NY) 17:81-98|
|Lin, Zhenjian; Koch, Michael; Abdel Aziz, May Hamdy et al. (2014) Oxazinin A, a pseudodimeric natural product of mixed biosynthetic origin from a filamentous fungus. Org Lett 16:4774-7|
|Olivera, Baldomero M; Showers Corneli, Patrice; Watkins, Maren et al. (2014) Biodiversity of cone snails and other venomous marine gastropods: evolutionary success through neuropharmacology. Annu Rev Anim Biosci 2:487-513|
|Imperial, Julita S; Cabang, April B; Song, Jie et al. (2014) A family of excitatory peptide toxins from venomous crassispirine snails: using Constellation Pharmacology to assess bioactivity. Toxicon 89:45-54|