Abstract

Insects use their sense of smell to locate food, avoid environmental dangers, recognise kin and identify potential mates. Despite a wealth of data on the neuroanatomy and physiology of their olfactory circuits, remarkably little is known about the molecular basis of insect olfaction. Insect odorant receptors (ORs) contain seven predicted transmembrane domains, which has led to the prevailing assumption that they – like mammalian ORs – are members of the G protein-coupled receptor (GPCR) superfamily.

I have challenged this dogma, through my demonstration that Drosophila ORs are structurally and functionally distinct from their mammalian counterparts. I have found that insect ORs adopt an inverted membrane topology relative to GPC Rs, with their N-termini and most highly conserved loops in the cytoplasm. Moreover, these receptors do not exist in a monomeric state but rather associate via these loops with OR83b, a broadly expressed member of the OR family. OR83b appears to act as an olfactory co-receptor that is essential to transport and maintain the heteromeric OR/OR83b complex in the sensory cilia.

Given this evolutionarily unique molecular design of the Drosophila odorant receptor, I reasoned that other components of olfactory signalling pathways might also be specific to insects. To identify such molecules, I have initiated a comparative genomics approach, through in silico analysis of Drosophila, mosquito and vertebrate genome sequences. I have identified approximately fifty novel genes that are expressed specifically or highly enriched in olfactory sensory neurons. I will describe this screening strategy and present my functional characterisation of some of the identified genes. Such insect-specific molecules represent excellent candidate targets for custom-designed insect repellents to inhibit the olfactory-driven behaviours of agricultural pests and disease vectors.