Grant: Research Tools and Instruments - Category 1 (<$150,000)

Proposed instrumentation for discovery of cancer subtypes through analysis of miRNA signatures is crucial for our research program concerned with the development of technologies for personalized cancer medicine. Within each cancer type there are multiple subtypes that exhibit different levels of malignancy and require different therapies. MiRNAs are very promising molecular markers for accurately identifying cancer subtypes as every cancer subtype is presumably associated with a unique quantitative miRNA signature. Despite successful efforts to identify candidate miRNA markers of cancer, miRNA signatures have not yet been used for the discovery of cancer subtypes. The lack of a miRNA analysis technology that is (i) quantitative, (ii) highly-sensitive, (iii) rugged, and (iv) capable of simultaneously analyzing multiple miRNAs is arguably the major challenge on our way to practical use of miRNA markers in personalized cancer medicine. Our research program focuses on the development of a suitable technology. The instrumental platform for this technology is our recent invention: capillary electrophoresis (CE) with confocal time-resolved fluorescence detection through an embedded capillary interface. The methodological platform is our other recent invention: a CE-based direct quantitative analysis of multiple miRNAs. Here we propose to assemble an instrument for analysis of miRNA signatures with a sensitivity equivalent to 1 copy of miRNA per cell. Four trainees (1 undergraduate student, 2 graduate students, and 1 PDF) are currently working on miRNA detection projects supported by two operating grants totaling 140,000 per year. Training of these researchers critically depends on the availability of the proposed instrument. If the laboratory does not get the instrument in 2013 then our research in this direction will be stalled. This, in turn, could result in the loss of our leading position in direct miRNA detection research. The delay in acquiring the proposed instrument would also dramatically affect the HQP training process.