This year’s Journal Club will highlight the evolution of methods utilized to assess the physiological role and function of odorant receptors since their discovery in 1991 by Buck and Axel.

We will start by reviewing Zhao et al.’s 1998 paper, “Functional expression of a mammalian odorant receptor,” in which the authors accomplished rat I7 receptor expression in its native environment, the olfactory sensory neuron, via recombinant adenovirus. The authors found this receptor is selective for C7 to C10 saturated aliphatic aldehydes although they did not resolve how those odorants physically interact with receptor binding sites. However, this and other expression approaches launched decades of additional work to identify ligands for the family of odorant receptors.

While much progress has been made, a recent review by Lalis et al observed that a ligand has not been identified for approximately half of the known receptor variants. Thus, our discussion will include the 2024 paper by de March et al. “Engineered odorant receptors illuminate the basis of odour discrimination,” and its application of cryo-EM to the long unresolved problem of describing odorant receptors protein structure. This exciting advancement furthers our understanding of the molecular determinants of ligand selectivity and will enable further deorphanization via in silico methodologies.

AGENDA

• Introduction (Jessica H. Brann, Ph.D., dsm-firmenich, New York, NY, USA)
• Classic publication: Functional expression of a mammalian odorant receptor - PubMed (Ricardo Araneda, Ph.D., University of Maryland, College Park, MD, USA)
• Recent publication: Engineered odorant receptors illuminate the basis of odour discrimination - PubMed (Mona Marie, Ph.D., Molecular Genetics and Microbiology Department, Duke University School of Medicine, Durham, NC, USA)