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

阐明嗅觉缺失和嗅觉正常个体嗅觉训练的气味受体相关机制

• 批准号: 468981129
• 负责人: Professor Dr. Thomas Hummel
• 金额: --
• 依托单位: Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/468981129?language=en
• 关键词: Clarifying; odorant; receptor; related; mechanisms

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

了解关键食物气味物质的受体密码是了解与食物相关的特异性嗅觉障碍机制的先决条件。它既可以通过例如非功能性或单倍型的频率来预测未知的特定嗅觉缺失的频率，也可以了解已知类型的特定嗅觉缺失的潜在分子机制。在该项目中获得的关于特定嗅觉丧失机制的知识将有助于指导感官面板的组装，并最终可能通过满足消费者群体或个人的需求和能力来实现灵活的食品生产，承认基于化学感官的食品享乐学评估仍然是消费者选择的主要驱动力。关于嗅觉训练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)用与嗅觉缺失相关的关键食物气味使ORs去孤儿将使我们能够破译特定嗅觉丧失的受体密码，使得可能由相同的单一气味激活的单个、特定OR或最敏感的ORs将决定无嗅觉表型，从而验证同源气味/或配对的生物学相关性，(Ii)一个人可以通过训练改善感染后全身性嗅觉障碍患者对单一化合物的嗅觉，因为嗅觉信号主要不是被废除的而且(Iii)这种改善的嗅觉涉及编码那些对所研究的气味有反应的受体的基因转录水平的增加。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，弗里辛)，以及大型患者/受试者集体、详细的感官研究和活组织检查(Hummel实验室，德累斯顿)。具体目标是：目标1-针对特定嗅觉缺失的嗅觉训练前后的无嗅觉个体的鉴定、化学感官评价和刷检目的2-破译特定嗅觉缺失的受体密码目标3-针对特定嗅觉缺失的ORs对个体进行基因分型目标4-对正常受试者和感染后的全身性嗅觉障碍患者在嗅觉训练前后的受体特异性转录水平进行量化