A Household Yeast Biosensor for Cholera

霍乱家用酵母生物传感器

• 批准号: 9275835
• 负责人: VIRGINIA W CORNISH
• 金额: $ 70.93万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-15 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9275835
• 关键词: Africa; African; Anabolism; Antibodies; Benchmarking; Binding; Biosensor; Bioterrorism; Cause of Death; Centers for Disease Control and Prevention (U.S.); Cholera; Cholera Toxin; Communities; Country; Coupling; Detection; Developing Countries; Development; Diagnostic; Directed Molecular Evolution; Disease; Dried Yeast; Engineering; Epidemic; Epitopes; Equipment; Evolution; Eye; Faculty; Feces; Feedback; Fermentation; Food Safety; Formulation; Freeze Drying; Fungal Peptides; G Protein-Coupled Receptor Signaling; G-Protein-Coupled Receptors; GTP-Binding Protein alpha Subunits, Gs; Goals; Grant; Hand; Health; Hospitals; Hour; Household; Household Products; Human; Hybrids; Infection; Laboratories; Ligands; Methods; Monitor; Noise; Parents; Peptides; Pigments; Plants; Positioning Attribute; Public Health; Reaction Time; Reagent; Reporter; Resources; Risk; Saccharomyces cerevisiae; Scientist; Series; Signal Transduction; Specificity; System; Technology; Testing; Tomatoes; Translating; Universities; Validation; Vibrio cholerae; Visual; Water Supply; Yeasts; base; clinical practice; cost; design; field study; improved; killings; lycopene; metabolic engineering; pathogen; product development; prototype; public health relevance; receptor; response; surveillance network; synthetic biology; tool; water sampling

 DESCRIPTION (provided by applicant): Diarrheal diseases are one of the top ten causes of death in developing countries, with V. cholerae being one of the principal bacterial causative agents annually infecting an estimated ~4 million and killing ~120,000 people. Although an easily treatable disease, cholera continues to cause fatal epidemics because in practice clinical detection rarely occurs outside remote hospitals and environmental detection in water supplies remains challenging. The state-of-the- art for cholera diagnostics are purified antibodies used as dipstick tests; unfortunately dipstick tests are prohibitively expensive and unstable for use directly in local communities where cholera is endemic. A new transformative mode of detection will be needed to generate an extremely cheap and widely distributable system for continuous local surveillance of cholera. We sought to overcome current obstacles to local diagnostics by using existing synthetic biology components to craft a new class of cheap and simple diagnostic built around freeze-dried yeast. We avoid the need for expensive equipment and additional reagents by engineering yeast to produce the red tomato pigment lycopene in response to the cholera pathogen. We envision that engineered baker's yeast can be freeze-dried and then globally distributed to provide an inexpensive, safe, simple and reliable tool for monitoring of cholera in communities at risk for infection. If successful, this yeast platform will be easily redeployable for the detection of other pathogens.

 描述（由申请人提供）：腹泻病是发展中国家的十大死因之一，霍乱弧菌是主要的细菌病原体之一，每年估计感染约400万人，造成约120，000人死亡。虽然霍乱是一种容易治疗的疾病，但它继续造成致命的流行病，因为在实践中，在偏远医院以外很少进行临床检测，而且供水中的环境检测仍然具有挑战性。霍乱诊断的最新技术是用作试纸测试的纯化抗体;不幸的是，试纸测试非常昂贵，并且不稳定，无法直接用于霍乱流行的当地社区。将需要一种新的变革性检测模式，以产生一种极其廉价和可广泛分发的系统，用于持续的地方霍乱监测。我们试图通过使用现有的合成生物学组件来克服当前本地诊断的障碍，以围绕冻干酵母构建一类新的廉价和简单的诊断。我们避免了昂贵的设备和额外的试剂的需要，通过工程酵母生产红番茄色素番茄红素，以应对霍乱病原体。我们设想，工程面包酵母可以冷冻干燥，然后在全球范围内分发，以提供一种廉价，安全，简单和可靠的工具，用于监测有感染风险的社区的霍乱。如果成功，这种酵母平台将很容易重新部署用于检测其他病原体。