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. .

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM099939-01
Application #
8219706
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Krasnewich, Donna M
Project Start
2012-02-13
Project End
2015-12-31
Budget Start
2012-02-13
Budget End
2012-12-31
Support Year
1
Fiscal Year
2012
Total Cost
$284,050
Indirect Cost
$94,050
Name
University of Utah
Department
Genetics
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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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
Yandell, Mark; Ence, Daniel (2012) A beginner's guide to eukaryotic genome annotation. Nat Rev Genet 13:329-42