Insights in to venom and toxin activities and pharmacological/therapeutic potential using gene expression profiling

Abstract

Traditionally, venoms are assessed, usually following a standard list of potential activities including hypotensive, hemorrhagic, edema and neurotoxicity. This is then followed by the search of toxins in the venoms which contribute to the observed pathophysiological effect. Typically this is done by isolation of the toxin from the venom via biochemical procedures. Alternatively, toxins are cloned and expressed from cDNA libraries generated from venom gland RNA followed by assessment of biological/biochemical function and ultimately pathophysiological effect on the experimental model. These approaches have provided the field with a rich understanding of the potential role of toxins, but may fall short in terms of fully describing the actual function of the toxin in the context of the whole venom and whole animal. This mode of investigation likely does not provide a full understanding of the complete range of biological activities of the venoms and toxins since the suite of assays conducted are generally limited. One data-rich approach that has recently been exploited for further understanding the biological activities and functional potential of venoms and toxins is the study of their ability to alter gene expression in the host. This chapter will discuss how this approach may be of value in terms of drug discovery based on venom produced alteration of gene expression profiles using Connectivity Maps.