Bitter Human Taste Bud Epithelial Cell Platforms for Bitter Taste Antagonist Discovery

用于苦味拮抗剂发现的人类苦味芽上皮细胞平台

• 批准号: 9912248
• 负责人: DANIELLE Renee REED
• 金额: $ 1.54万
• 依托单位: DISCOVERYBIOMED, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9912248
• 关键词: Address; Agonist; Beverages; Biological Assay; Botanicals; Businesses; CDK4 gene; Calcium; Cell Culture Techniques; Cell Line; Cell Survival; Cell membrane; Cells; Chemicals; Child; Childhood; Clinical; Clone Cells; Cloning; Collaborations; Collection; Data; Detection; Drug Industry; Elderly; Ensure; Epithelial Cells; Food; Genetic; Genotype; Goals; Harvest; Health; Health Benefit; Healthy Eating; Human; Image; Industry; Institution; Intellectual Property; Intention; Joints; Large T Antigen; Maintenance; Masks; Measurement; Medicine; Membrane; Membrane Potentials; Methods; Natural Products; Neurotransmitters; Nutritional; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phenotype; Physiological; Phytochemical; Plants; Population; Positioning Attribute; Principal Investigator; Public Health; RNA-Directed DNA Polymerase; Research; Sensory; Signal Transduction; Simian virus 40; Small Business Technology Transfer Research; Small T Antigen; Smell Perception; Sodium Chloride; Source; Stimulus; System; Taste Buds; Taste Perception; Taste aversion; Telomerase; Testing; Time; Tongue; Validation; Variant; afferent nerve; base; cell immortalization; compliance behavior; design; food challenge; food flavor; food insecurity; grasp; high throughput screening; immortalized cell; improved; interest; liquid formulation; meetings; neurotransmitter release; novel; overexpression; public health relevance; receptor function; reduced food intake; response; screening; small molecule libraries; sugar; voltage; voltage sensitive dye

Principal Investigators for Small Business: DiscoveryBioMed, Inc. (DBM) and Monell Chemical Senses Center Project Summary Abstract Bitter taste in foods and medicines presents a barrier to overcoming global public health challenges: food insecurity, poor nutritional health, and poor compliance with medication use, particularly among children and the elderly. Sugar and salt, the mainstays to address these challenges, further erode nutritional health, and current alternatives have adverse taste attributes of their own. We propose to develop a reliable, human taste- cell screening platform to find bitter blockers of commercial interest to the food, flavor, and pharmaceutical industries, with the aim to improve the taste and acceptance of nutritious and sustainable foods and medicines. This Phase 1 STTR proposal has the following goals: (a) to establish immortal human taste-bud-derived epithelial cell cultures and lines (i.e., hTBEC platforms) from donors with bitter-sensitive genotypes and (b) to design, optimize, and implement hTBEC-based bioassays of bitter taste receptor function and other key end points to produce readout data for high-throughput screening (HTS). This proposed research is the initial step toward our ultimate goal of executing a full HTS-based campaign to discover and validate bitter taste receptor antagonists from phytochemicals, phytochemical derivatives, and botanical extracts and extract fractions. This commercial-academic collaboration between DiscoveryBioMed, Inc. and Monell Chemical Senses Center brings together expertise in (a) culture of human taste cells, (b) the creation of immortalized cell lines, (c) HTS, and (c) genetics and human sensory analysis. The hypothesis is that hTBEC-platform-based bioassays will provide a more relevant and robust way to identify new bitter antagonists, given the imperfect current methods of overexpressing known taste receptors in heterologous cells. The discovery of bitter taste receptor antagonists that alone or blended will block bitter taste can improve healthy eating by reducing reliance on salt and sugar and can improve compliance by patients taking medicines. Thus, new bitter blockers will improve human health. PHS 398/2590 (Rev. 09/04, re-issued 4/2006) Page Continuation Format Page

小型企业的主要调查人员：DiscoveryBioMed，Inc.(DBM)和Monell化学传感中心 项目摘要摘要 食品和药品的苦味是克服全球公共卫生挑战的障碍：食品 不安全、营养健康差和服药依从性差，特别是在儿童和 老年人。糖和盐是应对这些挑战的支柱，进一步侵蚀了营养健康，以及 目前的替代品都有自己不利的品味属性。我们建议开发一种可靠的、人性化的品味- 细胞筛选平台，寻找对食品、香料和药品有商业利益的苦味阻滞剂 工业，目的是提高人们对营养和可持续食品和药品的品味和接受度。 这项第一阶段的STTR提案有以下目标：(A)建立不朽的人类味蕾来源 来自苦味敏感型捐赠者的上皮细胞培养和系(即hTBEC平台)和(B)至 设计、优化和实施基于hTBEC的苦味感受器功能和其他关键端的生物检测 为高通量筛选(HTS)提供读数数据。这项拟议的研究是第一步 我们的最终目标是执行基于HTS的全面活动，以发现和验证苦味感受器 来自植物化学物质、植物化学衍生物以及植物提取物和提取物的拮抗剂。这 DiscoveryBioMed，Inc.与Monell化学传感中心之间的商业-学术合作 汇集了(A)人类味觉细胞培养，(B)永生化细胞系的创建，(C)HTS， 以及(C)遗传学和人类感官分析。假设基于hTBEC平台的生物检测将 提供一种更相关和更强大的方法来识别新的苦涩对手，考虑到当前方法的不完善 在异种细胞中过度表达已知的味觉受体。苦味感受器的发现 单独或混合使用可以抑制苦味的拮抗剂可以通过减少对盐的依赖来改善健康饮食 和糖，并可以提高患者服药的依从性。因此，新的苦涩拦网将会有所改善。 人类健康。 PHS 398/2590(09/04版，2006年4月4日重新发布)页面续格式页面