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: 8544479
• 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/8544479
• 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）将其研究专长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，到用于医疗效益的基于dna的纳米技术，将发生系统的转变。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博士的指导下进行5年的教学性生物医学培训。这种早期职业转型的主要原因包括：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天生渴望在纳米尺度上理解和控制物质，以造福人类，iv) DNA纳米技术为NIH的使命做出贡献的能力，同时为PI提供智力奖励。v)与爱达荷州卓越生物医学研究理念网络（INBRE）和山地州肿瘤与医学研究所（MSTMRI）合作并获得技术支持的潜力。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 （miRNAs）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超越定量逆转录聚合酶链反应（qRT-PCR）性能的肺癌体外诊断工具。基于相对miRNA浓度，金纳米颗粒聚集将表示疾病的阳性/阴性信号，类似于一次性妊娠试纸的结果。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，因为它可能在全球范围内催化低成本的早期疾病诊断。此外，所提出的方法是创新的，因为它使用了一种完全不同的、基于非pcr的方法来检测mirna。在导师的监督下，私家侦探将从教学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)参加美国国立卫生研究院的生物跟踪课程，以获得实验技术方面的先进知识；iii)参加圣卢克医学中心的每月MSTMRI研讨会和案例研究，以参与医学界；iv)与导师讨论每周的研究成果，以支持PI的实验、理论和研究行为发展。v)继续与导师共同教授一个期刊俱乐部，以促进DNA纳米技术领域的科学素养；vi)继续教授高年级生物材料课程，以加强教学相长；vii)参加诸如材料研究学会（MRS）和纳米科学基础（FNANO）等会议，以建立联系；viii)与导师一起或独立撰写提案。