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.
The goal of this research is to develop a point-of-contact device for detecting lung cancer via engineered reactions between synthetic DNA components and disease-specific micro-RNAs (miRNAs) found in bodily fluids. As miRNAs are linked to over 180 diseases including cardiovascular, neurological, muscular, sexually transmitted, obesogenic, and diabetic, this device may impact healthcare by facilitating accurate self-diagnosis of disease on a global scale. The test will only require the mixing together of four fluids, including bodily fluid from the patient, a liquid-based nucleic acid substrate, a liquid-based nucleic acid fuel, and a liquid based reporter complex.
|Zhirnov, Victor; Zadegan, Reza M; Sandhu, Gurtej S et al. (2016) Nucleic acid memory. Nat Mater 15:366-70|
|Goltry, Sara; Hallstrom, Natalya; Clark, Tyler et al. (2015) DNA topology influences molecular machine lifetime in human serum. Nanoscale 7:10382-90|
|Cannon, Brittany L; Kellis, Donald L; Davis, Paul H et al. (2015) Excitonic AND Logic Gates on DNA Brick Nanobreadboards. ACS Photonics 2:398-404|
|Takabayashi, Sadao; Klein, William P; Onodera, Craig et al. (2014) High precision and high yield fabrication of dense nanoparticle arrays onto DNA origami at statistically independent binding sites. Nanoscale 6:13928-38|
|Klein, William P; Schmidt, Charles N; Rapp, Blake et al. (2013) Multiscaffold DNA origami nanoparticle waveguides. Nano Lett 13:3850-6|
|Huttanus, Herbert M; Graugnard, Elton; Yurke, Bernard et al. (2013) Enhanced DNA sensing via catalytic aggregation of gold nanoparticles. Biosens Bioelectron 50:382-6|
|Graugnard, Elton; Kellis, Donald L; Bui, Hieu et al. (2012) DNA-controlled excitonic switches. Nano Lett 12:2117-22|