Low Cost Diagnosis of Disease using Synthetic DNA Reactions

描述(由申请人提供)：这份由K25指导的定量研究发展奖申请书概述了首席调查员(PI)转变其研究专长以成为国家卫生研究院(NIH)独立调查员的必要背景、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，到以DNA为基础的用于医疗的纳米技术，将发生一个系统的转变。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博士的指导下进行为期5年的生物医学教学培训。这一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未受过生物科学方面的正式培训，iii)PI内在渴望在纳米尺度上了解和控制物质以造福人类，iv)DNA纳米技术在为PI提供智力奖励的同时为NIH的使命做出贡献的能力，以及v)与爱达荷州IDEA生物医学研究卓越网络(INBRE)和山州肿瘤与医学研究所(MSTMRI)合作并接受其技术支持的潜力。K25奖的目标是设计一种快速、低成本、一次性的肺癌检测系统，通过人工合成DNA成分与人类血液中发现的疾病特异性微型RNA(MiRNAs)之间的工程化反应。K25奖的目标是在体外建立一种超过定量逆转录聚合酶链式反应(qRT-PCR)表现的肺癌诊断工具。根据miRNA的相对浓度，金纳米颗粒的聚集将标志着疾病的阳性/阴性信号，类似于一次性怀孕测试的结果。由于miRNAs与心血管、神经、肌肉、性传播、肥胖和糖尿病疾病有关，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疾病早期诊断。此外，建议的方法是创新的，因为它使用了一种完全不同的、非基于PCR的方法来检测miRNAs。在导师的监督下，PI将从教学性学习过渡到研究自主。授课活动包括：i)在博伊西州立大学参加生物化学课程，为生物科学奠定基础；ii)在NIH参加Bio-Track课程，获得实验技术方面的高级知识；iii)每月参加MSTMRI研讨会和圣卢克医学中心的案例研究，以参与医学界；iv)与导师讨论每周的研究结果，以支持PI的实验、理论和研究开发；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)参加材料研究学会(MRS)和纳米科学基金会(FNANO)等会议，以建立网络；viii)与导师一起撰写提案，并独立于导师。

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.