Genomics-based venom studies using the cone snail C. bullatus. The marine snail, Conus bullatus is a fish predator and must quickly immobilize its prey. This is accomplished by injecting prey with a lethal cocktail of conopeptide venoms, small cysteine-rich peptides, each with a high affinity to a different ligand or voltage- gated ion channel. Over the last decade, cone venoms have proven indispensable reagents for the study of vertebrate neurotransmission, and the FDA has approved one for the treatment of chronic pain. There is good reason to believe that collectively the cone snails still harbor a large repertoire of uncharacterized venoms (<100,000) of pharmacological interest. Conopeptides also undergo many unusual posttranslational modifications, carried out by enzymes that are themselves of pharmacological interest. This process of venom maturation is poorly characterized. Unfortunately, cone venom research today is hindered by a lack of significant genomic resources. Hence, the purpose this application is (1) to obtain funds for Conus transcriptome and genome sequencing and analyses to identify new venoms and their posttranslational modifiers, and (2) for functional characterizations of these new venoms and the enzymes involved in their posttranslational modifications. .
This project will use high-volume DNA and RNA sequencing to identify and characterize new venom genes in cone snails. This is important because these venoms are useful for vertebrate neurobiology research and as drugs for control of chronic pain. Discovering and characterizing more cone venoms will thus further both basic research and human health.
|Robinson, Samuel D; Li, Qing; Lu, Aiping et al. (2017) The Venom Repertoire of Conus gloriamaris (Chemnitz, 1777), the Glory of the Sea. Mar Drugs 15:|
|Robinson, Samuel D; Li, Qing; Bandyopadhyay, Pradip K et al. (2017) Hormone-like peptides in the venoms of marine cone snails. Gen Comp Endocrinol 244:11-18|
|Li, Qing; Barghi, Neda; Lu, Aiping et al. (2017) Divergence of the Venom Exogene Repertoire in Two Sister Species of Turriconus. Genome Biol Evol 9:2211-2225|
|Safavi-Hemami, Helena; Li, Qing; Jackson, Ronneshia L et al. (2016) Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides. Proc Natl Acad Sci U S A 113:3227-32|
|Safavi-Hemami, Helena; Lu, Aiping; Li, Qing et al. (2016) Venom Insulins of Cone Snails Diversify Rapidly and Track Prey Taxa. Mol Biol Evol 33:2924-2934|
|Safavi-Hemami, Helena; Gajewiak, Joanna; Karanth, Santhosh et al. (2015) Specialized insulin is used for chemical warfare by fish-hunting cone snails. Proc Natl Acad Sci U S A 112:1743-8|
|Safavi-Hemami, Helena; Hu, Hao; Gorasia, Dhana G et al. (2014) Combined proteomic and transcriptomic interrogation of the venom gland of Conus geographus uncovers novel components and functional compartmentalization. Mol Cell Proteomics 13:938-53|
|Ul-Hasan, Sabah; Burgess, Daniel M; Gajewiak, Joanna et al. (2013) Characterization of the peptidylglycine ?-amidating monooxygenase (PAM) from the venom ducts of neogastropods, Conus bullatus and Conus geographus. Toxicon 74:215-24|
|Hu, Hao; Bandyopadhyay, Pradip K; Olivera, Baldomero M et al. (2012) Elucidation of the molecular envenomation strategy of the cone snail Conus geographus through transcriptome sequencing of its venom duct. BMC Genomics 13:284|
|Yandell, Mark; Ence, Daniel (2012) A beginner's guide to eukaryotic genome annotation. Nat Rev Genet 13:329-42|
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