Structure, function, and evolution of chemosensory receptors
We have a longstanding interest in the molecular basis of odour detection by the Ionotropic Receptor (IR) family of chemosensory receptors, which have derived from the ancestral ionotropic glutamate receptor family of ligand-gated ion channels. Through comprehensive comparative bioinformatic analyses of IR repertoires in animal genomes, we have studied the evolutionary origin, expansion and diversification of this family of chemosensory receptors, and how this relates to individual species’ chemosensory ecology. Using electrophysiological and cell biological approaches in vivo and heterologous cells, we have studied IR complex formation and stoichiometry, and their trafficking, ion conduction and ligand-recognition properties. Our results provide insights into the conserved and distinct architecture of these chemosensory receptors and their synaptic ancestors. In current work, we collaborate with structural biologists Rongsheng Jin and Chun Tang to visualise the three-dimensional organisation and dynamics of the apo and odour-bound IR ligand-binding domain by X-ray crystallography and Nuclear Magnetic Resonance to understand the molecular basis and evolution of their odour recognition properties.
Pheromone signal transduction
Pheromones form one of the major sensory mechanisms by which animals communicate with members of their own species. These signals are often chemically distinct from other environmental chemical cues, because they derive from internal metabolic pathways, such as those for lipids or peptides. Consistently, the molecular machinery that detects pheromones also appears to be highly specialised. In previous work, we and others have characterised a set of proteins, including the olfactory receptor OR67d, the CD36-related transmembrane protein SNMP, and the extracellular Odorant Binding Protein, LUSH, which are each required for detection of the fatty acid-derived Drosophila sex pheromone cis -vaccenyl acetate (cVA). We are investigating the role of these proteins in mediating the sensitive and specific neuronal responses to cVA through in vivo structure-function and biochemical analysis.
Chemical biosensor development
Harnessing our knowledge of chemosensory receptors, we are involved in developing novel types of chemical biosensors as part of the Nano-tera Envirobot project. Our aim is to integrate known chemosensory receptors or custom-designed receptors of desired specificity into a chemosensing robot to enable remote and real time tracking of environmental pollutants.
Neuroanatomy and physiological functions of chemosensory circuits
We have completed a comprehensive neuroanatomical and physiological analysis of the IR olfactory circuits, in which we have identified odour ligands and central circuit organization for the vast majority of IR olfactory pathways. By comparing our findings with the properties of the circuits expressing Odorant Receptors (ORs), we can begin to explain how and why two complementary olfactory subsystems have evolved in insects. Recently, we have shown that a large number of IRs are selectively expressed in small subpopulations of neurons in peripheral and internal gustatory neurons, suggesting roles for these receptors in taste detection and internal food assessment. We are currently defining the ligands detected by these sensory pathways, identifying their higher order circuit elements and exploring the taste-evoked behaviours they underlie.
Olfactory circuit evolution
Much of our current work focuses on obtaining mechanistic explanations for how novel olfactory pathways evolve, through two main approaches. First, we are performing comparative transcriptomics analyses of olfactory subsystems, as well as of individual olfactory pathways within these subsystems, to identify and characterise loci that have driven the developmental and functional diversification of these sensory circuits. Second, we are expanding our efforts to genetic, physiological and behavioural analysis of drosophilid species that have distinct chemosensory preferences to D. melanogaster, to identify the genetic basis of their ecologically-important olfactory adaptations. Together these studies will provide general insights into the mechanisms of, and constraints on, brain evolution. Moreover, we anticipate that understanding how brains have been finely sculpted through random mutation and natural selection in the past may enable future directed manipulation of the connectivity and activity of neural circuits.
Chemosensory and social behaviours in flies and ants
We have used simple chemosensory preference assays to define the innate behaviours mediated by a number of olfactory and gustatory pathways. We have also examined the role of chemosensory signals in controlling sexual behaviours. Current efforts are directed towards development of novel behavioural assays in which we can precisely control the temporal pattern of odour stimuli, and video-track single or groups of flies in a high-throughput manner, together with the group of Dario Floreano (EPFL). These technical advances are allowing us to describe previously unobservable individual and group behaviours. Finally, in a new research direction, we are collaborating with Laurent Keller (DEE-UNIL) to study how chemical communication can control social organisation in a social insect, the carpenter ant Camponotus floridanus.