Wellcome Trust/DBT India Alliance
Kartik has been awarded a Wellcome Trust/DBT India Alliance Intermediate Fellowship!
The project, which would be pursued in collaboration with the Liverpool School of Tropical Medicine and the International AIDS Vaccine Initiative, aims at utilising our understanding of venom evolution for the innovation of pan-India effective snakebite therapy.
This project provides the Evolutionary Venomics Lab a novel (and parallel) direction to reaching India's Next Generation Recombinant Antivenoms.
In the Evolutionary Venomics Lab at the Centre for Ecological Sciences (CES), Indian Institute of Science (IISC), we investigate venomous animals and their venoms as model systems to address basic but broad questions in evolutionary biology and genetics. Using state-of-the-art technologies across multiple disciplines, we examine the fascinating evolutionary histories of the enigmatic lineages of venomous animals and their venoms.
A particular emphasis is placed on characterizing the composition, toxicity profiles and the evolutionary dynamics of venoms of the ‘big four’ snakes in India, as the lab will strive to deliver advanced antivenom with a commensurate improvement in safety, specificity, and affordability of treatment. The protein composition, and hence the pathogenic potential of venoms, can exhibit dramatic geographical variation, with different populations of the same species having starkly distinct venom profiles and, consequently, resulting in a significantly reduced antivenom efficiency. Therefore, the lab will unravel intra- and interspecific venom variability in medically significant Indian snakes and utilize this information for the molecular design of effective snakebite therapy.
The other broad aims of the lab include (a) investigating genomes, transcriptomes and proteomes of neglected venomous lineages (e.g., scorpions, spiders, centipedes, jellyfish, Hymenoptera, etc.) to understand the molecular basis of venom production, regulation, and evolutionary diversification; (b) understanding the genetic basis of venom resistance in the venomous animal and its prey/predators; (c) unraveling the evolutionary forces that have shaped the current distribution of venomous animals in the Indian subcontinent; and (d) investigating the therapeutic potential of venom proteins.
* Joint first authors # corresponding author
- Senji Laxme RR, Khochare S, DeSouza HF, Ahuja B, Suranse V, Martin G, Whitaker R and Sunagar K #. 2019. Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies (PLOS Neglected Tropical Diseases - in Press).
Sunagar K #, Moran Y. 2015. The Rise and Fall of an Evolutionary Innovation: Contrasting Strategies of Venom Evolution in Ancient and Young Animals. PLoS Genetics 11:e1005596.
Ujvari B*, Casewell NR*, Sunagar K*, Arbuckle K, Wuster W, Lo N, O'Meally D, Beckmann C, King GF, Deplazes E, Madsen T. 2015. Widespread convergence in toxin resistance by predictable molecular evolution. Proceedings of National Academy of Sciences U S A 112:11911-11916.
Sunagar K, Johnson WE, O'Brien SJ, Vasconcelos V, Antunes A. 2012. Evolution of CRISPs associated with toxicoferan-reptilian venom and mammalian reproduction. Molecular Biology Evolution 29:1807-1822.
Jouiaei M*, Sunagar K *, Federman Gross A, Scheib H, Alewood PF, Moran Y, Fry BG. 2015. Evolution of an ancient venom: recognition of a novel family of cnidarian toxins and the common evolutionary origin of sodium and potassium neurotoxins in sea anemone. Molecular Biology Evolution 32:1598-1610.
Sunagar K *, Undheim EA*, Scheib H*, Gren EC*, Cochran C, Person CE, Koludarov I, Kelln W, Hayes WK, King GF, Antunes A, Fry BG. 2014. Intraspecific venom variation in the medically significant Southern Pacific Rattlesnake (Crotalus oreganus helleri): biodiscovery, clinical and evolutionary implications. Journal of Proteomics 99:68-83.
Sunagar K #, Casewell NR, Varma S, Kolla R, Antunes A and Moran Y. “Deadly innovations: unravelling the molecular evolution of animal venoms” in the “Toxinology. Venom Genomics and Proteomics”, edited by P. Gopalakrishnakone. Springer Handbooks of Toxinology. p. 1-23
Fry BG, Koludarov I, Jackson TNW, Holford M, Terrat Y, Casewell NR, Undheim EAB, Vetter I, Ali SA, Low DHW and Sunagar K. 2015. Chapter 1 Seeing the Woods for the Trees: Understanding Venom Evolution as a Guide for Biodiscovery. In. Venoms to Drugs: Venom as a Source for the Development of Human Therapeutics: The Royal Society of Chemistry. p. 1-36.
The Origin and Evolution of the Toxicofera Reptile Venom System. B. G. Fry, Sunagar K, N. R. Casewell, E. Kochva, K. Roelants, H. Scheib, W. Wüster, N. Vidal, B. Young, F. Burbrink, R. A. Pyron, F. J. Vonk, and T. N. W. Jackson. Venomous reptiles and their toxins: Evolution, pathophysiology and Biodiscovery. (B. G. Fry, ed.), Oxford Press, USA. p. 1-33.
Our research is funded by the following agencies