Olfaction refers to the sense of smell. This sense is mediated by specialized sensory cells of the nasal cavity of vertebrates, and, by analogy, sensory cells of the antennae of invertebrates. Olfaction, along with taste, is a form of chemoreception. Olfaction is ideally suited to study the complex mechanism of transducing chemical into neuronal signals generating behavioral responses, which are essential for the survival of most mammals.

Olfactory receptors expressed in the cell membranes of olfactory receptor cells are responsible for the detection of odor molecules. Activated olfactory receptors are the initial player in a signal transduction cascade which ultimately produces a nerve impulse which is transmitted to the brain. These receptors are members of the class A rhodopsin-like family of G protein-coupled receptors (GPCRs). Each olfactory receptor cell possesses only one type of odorant receptor, and each receptor can detect a limited number of odorant substances. Olfactory receptor cells are therefore highly specialized for a few odors.

In the present work we aim to explore the molecular determinants of specific olfactory receptors. We have modeled the mouse Eugenol olfactory receptor based on the crystal structure of β2-adrenergic receptor. Based on this model, we have designed a series of site directed mutagenesis experiments to elucidate the structural determinants of receptor specificity on various chemically diverse odorant molecules. Additionally, using QSAR methods, we could computationally confirm that some synthetic sandalwood compounds (an important class of molecules used in the fragrance industry) have the capability to also activate the human nuclear estrogen receptor αlpha (ER) involved in transcriptional regulation of cellular differentiation and proliferation in a wide variety of tissues. Hence, these apparent dual active odorants induce distinct signal transduction pathways at different sub-cellular localizations, which affect both neuronal signaling, resulting in odor perception, and the ER-dependent transcriptional control of specific genes.