Rational design of DNA Nanostructures for disease diagnostics and prognostics

点击翻译按钮获取中文摘要

As the "omics" revolution has made abundantly clear, diseases manifest at the cellular level through myriad subtle changes in behaviour. For example, immune cells alter transcription patterns after encountering pathogens, as do cancerous cells in response to chemotherapeutics. These patterns have allowed the identification of a broad set of expression signatures with diagnostic potential for conditions ranging from infectious disease and diabetes to cancer and drug resistance. However, the technology to quickly and accurately recognize these characteristic signatures has yet to reach fruition. Hybridization-based technologies have excelled at ultraspecific recognition of numerous RNA sequences in parallel yet exhibit poor sensitivity; conversely, enzymatic reactions have achieved rapid detection of trace target concentrations yet lack the resolution to discern the subtle changes in evident in these expression signatures. The goal of this project will be to combine these two approaches, leveraging the specificity of rationally-designed hybridization systems with the sensitivity of enzymatic systems. The student will become skilled in the simulation-guided design of DNA nanostructures, modelling DNA interactions at hierarchical scales to engineer the desired sequence, domain, and whole-reaction dynamics. The student will apply these BioDesign principles to the diagnosis and prognosis of disease.