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

基本信息

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
项目类别：
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

项目摘要

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

小型企业首席研究员：DiscoveryBioMed, Inc. (DBM) 和 Monell Chemical Senses Center 项目概要摘要食品和药品中的苦味是克服全球公共卫生挑战的障碍：食品不安全感、营养健康状况不佳以及服药依从性差，尤其是儿童和青少年老年人。糖和盐作为应对这些挑战的支柱，进一步损害了营养健康，目前的替代品有其自身不良的口味属性。我们建议开发一种可靠的、人性化的品味—— 细胞筛选平台，用于寻找对食品、香料和药品具有商业利益的苦味阻滞剂行业，旨在提高营养和可持续食品和药品的口味和接受度。第一阶段 STTR 提案有以下目标： (a) 建立永生的人类味蕾源来自具有苦味敏感基因型的供体的上皮细胞培养物和细胞系（即 hTBEC 平台）和 (b) 设计、优化和实施基于 hTBEC 的苦味受体功能和其他关键终点的生物测定点以产生用于高通量筛选（HTS）的读出数据。这项拟议的研究是第一步实现我们的最终目标，即执行基于 HTS 的完整活动，以发现和验证苦味受体来自植物化学物质、植物化学衍生物以及植物提取物和提取级分的拮抗剂。这 DiscoveryBioMed, Inc. 与莫内尔化学感官中心之间的商业学术合作汇集了以下方面的专业知识：(a) 人类味觉细胞培养，(b) 永生化细胞系的创建，(c) HTS， (c) 遗传学和人类感官分析。假设基于 hTBEC 平台的生物测定将鉴于当前方法的不完善，提供了一种更相关和更稳健的方法来识别新的苦味拮抗剂在异源细胞中过度表达已知的味觉受体。苦味受体的发现单独或混合的拮抗剂可以阻止苦味，可以通过减少对盐的依赖来改善健康饮食和糖，可以提高患者服药的依从性。因此，新的苦味阻滞剂将改善人类健康。 PHS 398/2590（修订版 09/04，重新发布 4/2006）页继续格式页