EVOLUTIONARY AND TRANSLATIONAL VENOMICS
In any habitat of our planet, there is competition for resources, and every ecosystem on Earth supporting life contains venomous organisms. Venoms represent an adaptive trait and an example of both divergent and convergent evolution. Venoms comprise unique mixtures of deadly toxins tailored by Natural Selection in a prey-predator co-evolutionary arms race, and represent a sophisticated natural source of chemical and pharmacological novelty. In our laboratory we investigate structure-function correlations of the RTS-disintegrin jerdostatin, cloned from a venom gland cDNA library of the Chinese Jerdon’s pitviper Protobothrops jerdonii, which selectively blocks the function of the α1β1 integrin both in vitro and in vivo. Jerdostatin may represent a valuable lead compound for the development of anti-angiogenic drugs. On the other hand, snake envenoming constitutes a highly relevant public health issue in many tropical and subtropical countries. Snakebite envenoming has been recognised by the World Health Organization as a “neglected tropical disease”. According to the WHO’s “Global Burden of Disease 2010” study, it causes more than 125,000 deaths/year and a much larger number of victims suffering from permanent physical or emotional after-effects.
Adequate treatment of envenoming is critically dependent on the ability of antivenoms to neutralize the symptoms of systemic envenoming. Although the first antivenoms were produced more than 120 years ago, the lack of financial incentives for corporations to produce these serums, the shrinking of global markets and the weak leadership of public health organizations (both national and international) have left ignored the problem and its solution. The deficit of antivenom supply in certain regions of the world can be mitigated in part through the optimized use of existing antivenoms, and through the design of novel broad-range polyspecific antivenoms. A robust knowledge of the toxin composition and pathophysiological activities of venom proteomes is instrumental for the treatment of envenomed victims and for the selection of specimens for the generation of improved antidotes. Deconstructing the complex molecular phenotypes of snake venoms is now within the reach of “omic” tecnologies. A major research aim of our laboratoty is the development and application of proteomic tools (“venomics” and “antivenomics”) to study the natural history, composition, evolutionary, immunological trends of snake venoms, and their interaction with antivenoms.
Our Structural and Functional Venomics Laboratory collaborates with the Global Snakebite Initiative (http://www.snakebiteinitiative.org) which main aim is the mobilization and coordination of the resources, capabilities, know-how and synergies of research, clinical and technological development scientists, coming from the fields of venomics and toxinology, in order to search for solutions to snakebite envenoming.
For more detailed description of our research group interests, please consult:
Snake venomics and antivenomics: proteomic tools in the design and control of antivenoms for the treatment of snakebite envenoming. Gutiérrez, J.M. et al. J. Proteomics 72 (2009) 165-182
Ending the drought: new strategies for improving the flow of affordable, effective antivenoms in Asia and Africa. Williams, D.J. et al.. J. Proteomics 74 (2011) 1735-1767
Proteomic tools against the neglected pathology of snakebite envenoming. Calvete JJ. Exp. Rev. Proteomics 8 (2011) 739-758
The Need for Full Integration of Snakebite Envenoming within a Global Strategy to Combat the Neglected Tropical Diseases: The Way Forward. Gutiérrez et al. PLoS Negl. Trop. Dis. 7 (2013) e2162.
Snake venomics: from the inventory of toxins to biology. Calvete, J.J. Toxicon (2013) http://dx.doi.org/10.1016/j.toxicon.2013.03.020