8.

       Venom, amongst nature's most complex cocktails, has underpinned the evolutionary success of several lineages of animals. It has independently originated in at least 26 lineages of animals. Venom is defined as a complex cocktail that is secreted in a specialised gland or cell of an animal and is actively delivered to the target animal to facilitate defence or offence (i.e. feeding) of the venomous animal. This definition shows that venom is much more phylogenetically widespread than usually acknowledged, and venomous lineages include blood-feeding animals like vampire bats, lampreys, and ticks. Note that these sanguivorous animals use a complex cocktail of proteins to interfere with the coagulation of blood, and thus, facilitate their feeding. Venomous animals and their venoms are thus an excellent system to investigate fascinating concepts in evolutionary biology and ecology, including predator-prey evolutionary arms races, the origination of novel protein functions, the evolution of gene families associated with adaptations, etc.  The major themes of research in the lab include...

 

The introduction of next-generation of antivenoms in India

Snake venoms can vary dramatically in both composition and potency between species, and even within different populations of the same species (Sunagar et al. 2014, Journal of Proteomics). Therefore, this natural variation needs to be accounted for when producing antivenoms that are used in the treatment of snakebites. Unfortunately, in India antivenoms are still based on the venoms of a single southern population of snakes. However, it is impractical in a huge country like India to account for variation in venoms of all populations of all the medically significant species. Therefore, a particular emphasis will be placed in unravelling intra- and interspecific variation in venoms of Indian snakes and utilising this information for designing highly cost-effective and cross-neutralizing next-generation of antivenoms with an increased dose efficacy and specificity.

 

Sunagar K, Undheim EA, Scheib H, Gren E, Cochran C, Person C, Koludarov I, Kelln W, Hayes W, King GF, Antunes A and Fry BG. 2014. Intraspecific venom variation in the medically significant Southern Pacific Rattlesnake (Crotalus oreganus helleri): Biodiscovery, clinical and evolutionary implications. Journal of Proteomics.  doi: 10.1016/j.jprot.2014.01.013

 

Mechanisms of regulating venom compositions

The evolution of venom is tightly linked to the ecology of the venomous animal. Venom is often highly specific to the molecular targets of the natural prey or predatory animals. Since these animals can have very different physiologies, it is advantageous for the venomous animal to secrete highly specific but distinct toxin cocktails. During my postdoctoral research, I have investigated how different developmental stages of the sea anemone, Nematostella vectensis, can utilise different types of toxins for predation and defence (manuscript in Review). In the past, we have also shown how cone snails can inject a predation- and defence-specific cocktails of venom, depending on whether they are hunting for fish or defending themselves from predators (Duterte 2015. Nature Communications). However, the molecular mechanisms that shape venom compositions in animals have remained largely uninvestigated. To shed light on these systematic processes, some of the projects in the lab would investigate the molecular mechanisms (e.g., gene regulation) and mechanistic strategies underpin the regulation of venom compositions in animals.

 

The molecular evolution of venom

How do genes that code for venom originate from physiological protein coding genes? What are the underlying mechanisms that drive the evolution of toxin families? Experimental and bioinformatic approaches, including genomics and evolutionary analyses, will be utilised to understand the molecular mechanisms that underpin the transition of harmless physiological proteins into deadly toxins. In turn, this would further our understanding of the origin and diversification of novel protein functions.

 

Sunagar K and Moran Y. The Rise and Fall of an Evolutionary Innovation: Contrasting Strategies of Venom Evolution in Ancient and Young Animals. 2015. PLoS Genetics. 11(10): e1005596. doi: 10.1371/journal.pgen.1005596

 

Sunagar K, Jackson TNW, Undheim EAB, Ali S, Antunes A and Fry BG. 2013. Three-fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of snake venom toxins. Toxins. 5:2172-2208.

 

Some of the other lines of research in the lab include population genetics, phylogeography, and species phylogenetics of venomous animals, and drug discovery.