Clarifying the odorant receptor-related mechanisms of “olfactory training” in anosmic and normosmic individuals

• Applicants: Professor Dr. Thomas Hummel; Privatdozent Dr. Dietmar Krautwurst
• Subject Area: Otolaryngology, Phoniatrics and Audiology ; General Genetics and Functional Genome Biology ; Food Chemistry ; Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 468981129

Understanding the receptor code for key food odorants is a prerequisite for an under-standing of mechanisms of food-related specific anosmia. It may allow both the prediction of the frequency of yet unknown specific anosmia via the frequency of e.g. non-functional OR haplotypes, and an understanding of underlying molecular mechanisms of known types of specific anosmia. Knowledge gained on mechanisms of specific anosmia in this project will serve to guide the assembly of sensory panels, and finally may enable a flexible food production, by addressing the needs and abilities of consumer groups or individuals, acknowledging the fact that a chemosensory-based hedonic evaluation of food still is the major driver for consumer choice. Knowledge gained on molecular mechanisms of olfactory training will serve to guide approaches for treatment of patients with post infectious olfactory loss.We hypothesize that (i) a de-orphaning of ORs with anosmia-related key food odorants will enable us to decipher the receptor code of specific anosmia, such that a single, specific OR, or the most sensitive ORs that may be activated by the same, single odorant, will determine an anosmic phenotype, thereby validating the biological relevance of a cognate odorant/OR pairing, (ii) one can improve an olfactory perception of a single compound in individuals with specific and post infectious general anosmia by training, given that olfactory signaling is not principally abolished, and that (iii) this improved olfactory perception involves increased transcript levels of genes coding for those receptors that are responsive to the investigated odorant. The project combines the expertise of both labs: comprehensive receptor screening and de-orphaning, functional genomics, molecular genetics, and transcript analysis (Krautwurst lab, Freising), as well as large patient/subject collectives, detailed sensory studies, and biopsies (Hummel lab, Dresden). The specific aims are:Aim 1 – Identification of anosmic individuals, chemosensory evaluation, and brush-biopsies before and after olfactory training with odorants targeted at specific anosmiaAim 2 – Deciphering the receptor code of specific anosmiaAim 3 – Genotyping of individuals with respect to ORs related to a specific anosmiaAim 4 – Quantification of receptor-specific transcript levels in normosmic participants and individuals with specific and post infectious general anosmia, before and after olfactory training with odorants of specific anosmia

• DFG Programme: Research Grants