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

了解关键食物气味物质的受体密码是了解食物相关特异性嗅觉丧失机制的前提。它可以允许通过例如非功能性OR单倍型的频率来预测未知的特定嗅觉丧失的频率，以及理解已知类型的特定嗅觉丧失的潜在分子机制。在这个项目中获得的关于特定嗅觉丧失机制的知识将用于指导感官小组的组装，并最终通过满足消费者群体或个人的需求和能力，承认基于化学感官的食物享乐评价仍然是消费者选择的主要驱动力，从而实现灵活的食品生产。嗅觉训练的分子机制的知识将有助于指导感染后嗅觉丧失患者的治疗方法。我们假设：（i）与嗅觉缺失相关的关键食物气味剂的OR的去孤儿化将使我们能够破译特定嗅觉缺失的受体密码，例如单个，特定的OR，或可能被相同，单一气味剂激活的最敏感的OR，将确定嗅觉丧失表型，从而验证同源气味剂/OR配对的生物学相关性，（ii）可以通过训练改善具有特异性和感染后全身嗅觉丧失的个体中单一化合物的嗅觉感知，假定嗅觉信号传导基本上没有被消除，并且（iii）这种改善的嗅觉感知涉及编码对所研究的气味剂有反应的那些受体的基因的转录水平的增加。该项目结合了两个实验室的专业知识：全面的受体筛选和去孤儿，功能基因组学，分子遗传学和转录分析（Krautwurst实验室，Freising），以及大型患者/受试者集体，详细的感觉研究和活检（Hummel实验室，德累斯顿）。具体目标是：目标1 -嗅觉丧失个体的识别、化学感觉评估和针对特定嗅觉丧失的气味剂的嗅觉训练前后的刷活检目标2 -解密特定嗅觉丧失的受体密码目标3 -关于特定嗅觉丧失相关OR的个体的基因分型目标4 -定量嗅觉正常参与者和具有特定和感染后一般嗅觉丧失的个体在特定嗅觉丧失的气味剂的嗅觉训练前后的受体特异性转录水平

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