Investigating the diversity of immune molecular mechanisms in 'non-model' species.

To survive in an environment regularly exposed to fungal, bacterial, parasitic, and viral pathogens, the adaptive arm of the immune system of jawed vertebrates has constantly adapted over ~ 400 million years of evolution. While we have a good understanding of human and mouse immunity, our basic knowledge on how immunity operates in other species is largely unknown and unexplored. In the past decade, the development of technologies (e.g. genomics) has opened new exciting frontiers and novel opportunities to explore the diversity of immunity in species evolutionarily distant from humans and mice. For instance, in recent years, novel and unique immune receptors were discovered in a variety of species that include the NAR-TCR and Ig-NAR receptors in sharks, the unusual bovine antibodies (ultralong CDR-H3 paratopes) and the camelid single-domain antibodies. This immunogenetic variation across species clearly highlights how host immunity has convergently evolved to shape a diversity of molecular solutions for immune receptors and responses. Yet, the field of comparative immunology is sorely lacking protein chemistry and molecular approaches to fully understand the functioning of the immune system in those ‘non-model’ species that represent a veritable ‘gold mine’ of opportunities, where novel antigens, ligands, and immune receptors can be found, leading to high impact generalist findings and possible biotechnological applications. For instance, although discovered 30 years ago, we are beginning to realise the full therapeutic potential of the camelid single-domain antibodies (VHH) for the treatment of COVID 19 and cancer. It is also critically important to understand how the immune system operates in other species if we wish to protect species that are highly threatened by emerging and devastating diseases and that include iconic Australian wildlife. Our projects aim to transform our understanding of immune molecular mechanisms by investigating evolutionary diverse, 'non-model' species (e.g. Marsupials, bats, frogs) that exhibit unique and under explored modes of immune recognition. To do so, our projects employ a combination of molecular and cellular approaches that include protein chemistry, structural biology & mass spectrometry.