Poster Presentation 8th Venoms to Drugs 2023

Utilising blood-feeding arthropods to identify novel coagulotoxins and ion channel modulators (#108)

Raine S Mercedes 1 , Christina N. Zdenek 2 , Ram P Bhusal 3 , Stephen C Barker 4 , Glenn F King 1 , Bryan G Fry 4 , Andrew A Walker 1
  1. Institute of Molecular Biosciences, St Lucia, Queensland, Australia
  2. School of Biological Sciences, The University of Queensland, St Lucia, QLD, Australia
  3. Monash Biomedicine Discovery Institute, Monash University , Clayton, VIC, Australia
  4. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia

Haematophagous animals rely on the blood of vertebrates for nutrition, egg development, and survival. To obtain blood meals, these organisms have evolved salivary constituents that potently circumvent the host haemostatic response, which otherwise prevents blood loss by forming a blood clot. These salivary proteins can directly affect platelet aggregation, induce vasodilation and inhibit proteinases of the clotting cascade. There are over >15,000 species of blood-feeding invertebrates, and several of these animals' sialomes have been characterised. Antihaemostatic proteins have been isolated and developed within these sialomes as antithrombotic therapeutics. Consequently, examining the saliva of neglected haematophagous invertebrates could be pharmacologically relevant and provide further insight into evolutionary adaptions to blood-feeding.

 

Using proteotranscriptomic analyses, I aim to explore the salivary gland venom composition of underexplored haematophagous arthropods, including Australian native march flies (family Tabanidae) and Australian native Ixodid ticks, such as Ixodes holocyclusIxodes confusus, and, Ixodes tasmani. By examining their saliva, I hope to identify coagulotoxic molecules which allow them to overcome host haemostatic systems. In addition, I will examine the activity of holocyclotoxins from Ixodes holocyclus for the first time on their presumed target, CaV2 channels. Finally, I will characterise identified molecules both structurally and functionally to gain further knowledge into their role in the saliva of blood-feeding invertebrates. This research will expand the knowledge on the salivary toxins of blood-feeding invertebrates and discover new molecules with potential as therapeutics for thromboembolic disorders.