Molecular characterization of sensory function

感觉功能的分子表征

基本信息

批准号：
7753177
负责人：
Ardem Patapoutian
金额：
$ 41.13万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-03-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7753177
关键词：
Absence of pain sensation Acute Address Affect Alleles Amino Acids Analgesics Antifungal Agents Artificial Sweeteners Attention Behavior Behavioral Binding Biochemical Biological Biology Burn injury Calcium Camphor Capsaicin Cataloging Catalogs Cells Chemicals Chili Pepper Cinnamon - dietary Cloning Code Collaborations Cysteine Data Detection Distant Electrophysiology (science)Esthesia Ethnic Origin Exons Follow-Up Studies Future Gated Ion Channel Genetic Variation Genetic screening method Genus Mentha Goals Grant Heating Horseradish Human Image Indium Individual Inflammation Ion Channel Ion Channel Protein Isothiocyanates Libraries Ligands Link Mechanics Mediating Mediator of activation protein Menthol Miconazole Modality Modification Molecular Mus Mustard Mutagenesis Mutation Nature Neurons Nociception Pain Physiological Plant Extracts Plants Play Point Mutation Population Positioning Attribute Process Property Proteins Psychophysiology Publications Recurrent pain Relative (related person)Reporting Research Institute Role Saccharin Seminal Sensory Signal Transduction Site Stimulus Structure-Activity Relationship TRPV1 gene Temperature Temperature Sense Testing Therapeutic Uses Thermometers Touch sensation Transmembrane Domain Variant Work allicin base chronic pain cinnamic aldehyde clinically relevant design extracellular icilin in vivo insight mustard oil mutant novel public health relevance receptor research study response response to injury sensor somatosensory voltage

项目摘要

DESCRIPTION (provided by applicant): The sense of touch is unique in perceiving stimuli both physical (temperature, mechanical) and chemical (compounds that cause pain, itch, et cetera) in nature. In each modality, touch neurons distinguish noxious (painful) from innocuous stimuli, and the sensitization of touch neurons in response to injury and inflammation is the basis for many clinically-relevant chronic pain states. The molecules that mediate detection of touch stimuli have been a long-standing mystery. Recently, we and others have identified and characterized molecules responsible for sensing environmental temperature. These proteins are ion channels activated by distinct changes in thermal energy (in the noxious to innocuous range), thus functioning as the molecular thermometers of our body. We have found these same ion channels also act as chemosensors, and at least one of them is a polymodal sensor of physical and chemical damage. We wish to understand the activation process of thermoTRPs. Most fundamentally, how do these channels actually sense temperature at the molecular level? We will use a high- throughput random mutagenesis approach to address mechanism of thermoTRP activation. Our long-term goal is to synthesize a detailed molecular understanding of somatosensory neuron function. These studies aim to expand the fundamental understanding of basic sensory biology and are also expected to contribute to novel insights to treating pain. PUBLIC HEALTH RELEVANCE The studies described in this grant will address how ion channels involved in sensing pain and temperature are regulated. Information from these studies could potentially help in designing analgesic drugs.

描述（由申请人提供）：触觉在感知自然界的物理（温度、机械）和化学（引起疼痛、瘙痒等的化合物）刺激方面是独特的。在每种模式中，触觉神经元区分有害（疼痛）和无害刺激，并且触觉神经元对损伤和炎症的敏感化是许多临床相关慢性疼痛状态的基础。介导触摸刺激检测的分子长期以来一直是一个谜。最近，我们和其他人已经识别并表征了负责感知环境温度的分子。这些蛋白质是由热能的明显变化（在有害到无害的范围内）激活的离子通道，因此充当我们身体的分子温度计。我们发现这些相同的离子通道也可以充当化学传感器，其中至少有一个是物理和化学损伤的多模式传感器。我们希望了解thermoTRP 的激活过程。最根本的是，这些通道实际上如何在分子水平上感知温度？我们将使用高通量随机诱变方法来解决thermoTRP 激活机制。我们的长期目标是综合对体感神经元功能的详细分子理解。这些研究旨在扩大对基础感觉生物学的基本理解，并有望为治疗疼痛提供新的见解。公共健康相关性这项资助中描述的研究将解决如何调节参与感知疼痛和温度的离子通道。这些研究的信息可能有助于设计镇痛药物。