Low Cost Diagnosis of Disease using Synthetic DNA Reactions

使用合成 DNA 反应进行低成本疾病诊断

• 批准号: 8728938
• 负责人: William L. Hughes
• 金额: $ 13.68万
• 依托单位: BOISE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8728938
• 关键词: A549; Adopted; Amplifiers; Architecture; Area; Award; Behavior; Biochemistry; Biocompatible Materials; Biological Markers; Biological Sciences; Biomedical Research; Blood; Blood specimen; Cancer Detection; Cancer Diagnostics; Cardiovascular system; Case Study; Catalysis; Cells; Communities; Complex; DNA; Detection; Development; Devices; Diagnostic; Disease; Educational process of instructing; Engineering; Enrollment; Ensure; Exhibits; Extravasation; Feedback; Foundations; Gene Expression; Goals; Gold; Healthcare; Human; Humanities; Idaho; In Vitro; Journals; Kinetics; Knowledge; Learning; Length; Link; Liquid substance; Logic; Longevity; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Medical; Medical Research; Medical center; Mentors; Methods; MicroRNAs; Mission; Mus; Muscle; Nanostructures; Nanotechnology; Neurologic; Non-Small-Cell Lung Carcinoma; Nucleic Acids; Nucleotides; Nude Mice; Output; Patients; Performance; Plasma; Polymerase Chain Reaction; Pregnancy Tests; Procedures; Publishing; Reaction; Relative (related person); Reporter; Research; Research Institute; Research Personnel; Reverse Transcription; Rewards; Sampling; Serum; Signal Transduction; Silicon; Societies; Speed; Staging; Supervision; System; Techniques; Technology; Testing; Time; Training; Transistors; United States National Institutes of Health; Work; Writing; Zinc Oxide; base; cancer diagnosis; career; chemical reaction; cost; design; diabetic; disease diagnosis; in vivo; innovation; literacy; mouse model; nanoparticle; nanoscale; nanoscience; nuclease; prevent; professor; research and development; self diagnosis; symposium; synthetic construct; tool; tumor

DESCRIPTION (provided by applicant): This K25 Mentored Quantitative Research Development Award application outlines the necessary background for, the extensive commitment from, and the proposed plan by the Primary Investigator (PI) to transition his research expertise to become an independent investigator for the National Institutes of Health (NIH). A systematic transition will occur from the synthesis, discovery, and characterization of zinc oxide nanostructures for piezoelectric applications towards DNA-based nanotechnology for medical benefit. In support of this transition, the PI is requesting 5 years of didactic biomedical training under the supervision of Dr. Bernard Yurke, an internationally recognized physicist, biophysicist, and DNA nanotechnologist. Primary reasons for this early career transition include: i) the PI was hired as an Assistant Professor in the area of Biomaterials, ii) the PI was not formally trained in the biological sciences, iii) the PI's inherent desire to understand and control matter at the nanoscale for the benefit of humanity, iv) the ability for DNA nanotechnology to contribute to the mission of NIH while providing intellectual reward to the PI, and v) the potential to collaborate with and receive technical support from the Idaho Idea Network of Biomedical Research Excellence (INBRE) and the Mountain States Tumor & Medical Research Institute (MSTMRI). The goal of the K25 Award is to engineer a rapid, low-cost, disposable detection system for lung cancer via engineered reactions between synthetic DNA components and disease-specific micro-RNAs (miRNAs) found in human blood. The objective of the K25 Award is to build a diagnostic tool for lung cancer in vitro that exceeds the performance of quantitative reverse transcription polymerase chain reaction (qRT-PCR). Based on relative miRNA concentrations, gold nanoparticle aggregation will signify a positive/negative signal for disease, analogous to the results of a disposable pregnancy test. As miRNAs are linked to cardiovascular, neurological, muscular, sexually transmitted, obesogenic, and diabetic diseases, the proposed research is significant because it may catalyze low-cost, early-stage diagnosis of disease on a global scale. In addition, the proposed approach is innovative because it uses a radically different, non-PCR-based method for detecting miRNAs. Under mentor supervision, the PI will transition from didactic study to research independence. Didactic activities include: i) attending biochemistry courses at Boise State to establish a foundation in the biological sciences, ii) enrolling in Bio-Track courses at NIH to acquire advanced knowledge in experimental techniques, iii) attending monthly MSTMRI seminars and case studies at St Luke's Medical Center to engage the medical community, iv) discussing weekly research results with the mentor to support the experimental, theoretical, and research conduct development of the PI, v) continued co-teaching of a journal club with the mentor to facilitate scientific literacy in the area of DNA nanotechnology, vi) continued teaching of an upper-division Biomaterials course to reinforce learning via teaching, vii) participating in conferences such as the Materials Research Society (MRS) and Foundations of Nanoscience (FNANO) to network, and viii) writing proposals alongside and independent of the mentor.

描述（由申请人提供）：这份 K25 指导定量研究发展奖申请概述了主要研究者 (PI) 将其研究专业知识转变为美国国立卫生研究院 (NIH) 独立研究者的必要背景、广泛承诺和拟议计划。从用于压电应用的氧化锌纳米结构的合成、发现和表征到用于医疗用途的基于 DNA 的纳米技术，将会发生系统性的转变。为了支持这一转变，PI 要求在国际公认的物理学家、生物物理学家和 DNA 纳米技术专家 Bernard Yurke 博士的监督下进行 5 年的生物医学教学培训。这种早期职业转变的主要原因包括：i) PI 被聘为生物材料领域的助理教授，ii) PI 没有接受过生物科学方面的正式培训，iii) PI 内在地渴望理解和控制纳米尺度的物质以造福人类，iv) DNA 纳米技术有能力为 NIH 的使命做出贡献，同时为 PI 提供智力奖励，以及 v) 有潜力与爱达荷州生物医学卓越研究创意网络 (INBRE) 和山区国家肿瘤与医学研究所 (MSTMRI) 合作并获得技术支持。 K25 奖的目标是通过合成 DNA 成分与人类血液中发现的疾病特异性微 RNA (miRNA) 之间的工程反应，设计一种快速、低成本、一次性的肺癌检测系统。 K25 奖的目标是建立一种体外肺癌诊断工具，其性能超过定量逆转录聚合酶链反应 (qRT-PCR) 的性能。根据相对 miRNA 浓度，金纳米颗粒聚集将表示疾病的阳性/阴性信号，类似于一次性妊娠测试的结果。由于 miRNA 与心血管、神经、肌肉、性传播、肥胖和糖尿病疾病有关，因此拟议的研究具有重要意义，因为它可能会促进全球范围内的低成本、早期疾病诊断。此外，所提出的方法具有创新性，因为它使用一种完全不同的、非基于 PCR 的方法来检测 miRNA。 在导师的监督下，PI将从说教式学习过渡到独立研究。教学活动包括：i) 参加博伊西州立大学的生物化学课程，为生物科学奠定基础；ii) 参加 NIH 的 Bio-Track 课程，以获得实验技术方面的高级知识；iii) 参加圣卢克医学中心每月举行的 MSTMRI 研讨会和案例研究，以吸引医学界的参与；iv) 每周与导师讨论研究结果，以支持实验、理论和研究。 研究进行 PI 的发展，v) 继续与导师共同教授期刊俱乐部，以促进 DNA 纳米技术领域的科学素养，vi) 继续教授高级生物材料课程，通过教学加强学习，vii) 参加材料研究协会 (MRS) 和纳米科学基金会 (FNANO) 等会议以建立联系，viii) 一起撰写提案 并且独立于导师。