• campus:  a to z index
• map
• directory
• calendar

Search:

David R. Hillyard

Associate Professor of Biology

B.A. University of Utah

M.D. Columbia University

Research

References

 

 

Research

Conotoxin Genetics: Our lab focuses on an analysis of the very large and diverse family of genes encoding conotoxin peptides. Conus toxins are capable of discriminatory inhibition of individual subtypes of neuronal receptors. Furthermore, venoms are known to contain multiple variants of a given toxin type which inhibit different receptor subtypes. These molecules are therefore key to the functional characterization of the many emerging neuronal networks composed of multiple receptor subtypes. Initial work has suggested that Conus may use novel genetic strategies to carry out its prolific toxin design. We wish to understand how conotoxin genes are organized and how diversification is accelerated in this species. This work has as a parallel goal, the refinement of strategies to identify new classes and variants of conotoxins by methods of molecular biology.

Cone Snails express "families" of mRNAs which are organized into conserved and hypervariable regions. Probing for conserved nucleic acid sequences can quickly reveal families of conopeptides. Some of these conopeptide families, such as the Conus Magus w-conopeptides, are structurally homologous and target subtypes of a single receptor class (calcium receptors in this case). Others, such as the King Kong family are structurally related only by a conserved cysteine framework and may target a diversity of receptor targets. We are also interested in identifying the precursors of conotoxins and the mechanisms by which precise folding of very small cysteine rich peptides is achieved. Finally, we are interested in applying lessons from Conus molecular biology to the design of analogous peptide ligands by genetic engineering.

 

References