Novel Approaches to detect and treat sepsis

项目概要/摘要： 背景脓毒症是一种严重的危及生命的疾病，是死亡的最常见原因之一， 住院病人。脓毒症通常由细菌感染引起，包括革兰氏阴性菌和革兰氏阴性菌。 阳性细菌在美国，败血症患者的住院死亡率可能高达 41.1%，每年造成25万多人死亡，损失200亿美元。由于不足， 由于目前技术的敏感性和特异性，脓毒症诊断没有全球标准。在这 项目，PI的目标是解决脓毒症测试中特别关注的关键瓶颈，使用： 1)混合生物-无机纳米机器人，2）基于CRISPR的装置，和3）配备CRISPR的工程化机器人。 未来五年的目标。我们的第一个目标是用衣壳蛋白上的纳米抗体工程化噬菌体M13 尾丝蛋白pIII上的pVIII和His标签。在结合钴包覆的磁性纳米颗粒后， 混合生物-无机纳米机器人将用于浓缩和纯化血液样本中的病原体。捕获 将使用加标样品研究效率，然后进行临床研究。利用 CRISPR和微流控技术，第二个目标是制造便携式设备，以检测败血症相关 病原体，可用于资源有限的环境。最后一个目标是用不同的 CRISPR系统，可用于检测和对抗脓毒症相关的细菌病原体。接近尾声 到第五年，我们将把这些技术整合为脓毒症诊断的强大工具。 研究计划的总体构想。我们正在开发的技术将对世界产生广泛的影响。 生物医学研究社区检测和治疗败血症，甚至是其他疾病。我们的发达 技术还可以推进其他领域的病原体检测，如食品安全和环境保护。 监测.

Project Summary/Abstract: Background. Sepsis, a severe and life-threatening condition, is one of the most common causes of death in hospitalized patients. Sepsis is generally caused by bacterial infection, including both Gram-negative and positive bacteria. In the United States, the hospital mortality rate of patients with sepsis could be as high as 41.1%, which accounts for more than 250,000 deaths and $20 billion loss annually. Due to the inadequate sensitivity and specificity of the current technologies, there is no global standard for sepsis diagnosis. In this project, the PI has the ambition to address the critical bottlenecks specifically of concern in sepsis testing using: 1) hybrid bio-inorganic nanobots, 2) CRISPR-based devices, and 3) CRISPR-equipped engineered phages. Goals for the next five years. Our first goal is to engineer phage M13 with nanobodies on the capsid protein pVIII and his-tags on the tail fiber protein pIII. After binding cobalt-coated magnetic nanoparticles, the resulting hybrid bio-inorganic nanobots will be used to concentrate and purify pathogens from blood samples. Capture efficiency will be investigated using spiked samples and then proceed to clinical ones. Taking advantage of CRISPR and microfluidic technologies, the second goal is to fabricate portable devices to detect sepsis-related pathogens, which can be used in resource-limited settings. The last goal is to engineer phages with different CRISPR systems, that can be used to detect and combat sepsis-related bacterial pathogens. Towards the end of the fifth year, we will have integrated these technologies as a robust tool for sepsis diagnosis. Overall vision of the research program. The technologies we are developing will have a broad impact on the biomedical research communities to detect and treat sepsis, even for other diseases. Our developed technologies can also advance pathogen detection in other fields, such as food safety and environmental monitoring.