Our lab elicits new functions from DNA beyond that of its traditional role as Nature’s genetic material. DNA nanodevices are nanoscale assemblies, formed from a collection of synthetic DNA strands, that can have artificial function engineered into them. We have created quantitative imaging technology that uses DNA nanodevices as fluorescent reporters to map second messengers in real time in cells and in vivo. Until our innovation, it was not at all obvious whether such DNA nanodevices could function inside a living cell without being interfered with, or interfering with, the cells own networks of DNA control.
We have developed a range of strategies around this concept to interrogate diverse biological processes not previously amenable to analysis. We can now transform virtually any detection chemistry for various analytes into quantitative detection chemistries and localize that detection tissue-specifically in specific pre-designated subcellular locations in live organisms. Given the powerful ability to engineer a range of functionalities into DNA nanodevices, our lab seeks to create powerful biological imaging tools where none exist and unplug decades-old bottlenecks that have prevented quantitative measurements required to answer questions in systems biology.
Quantitative Functional Imaging
The versatile, functional imaging technology developed by us uses self-assembled DNA nanostructures to quantitatively image second messengers in real time, in living cells (1) and genetic model organisms (3). Why develop DNA nanodevices as fluorescent reporters when a range of fluorescent proteins exist? DNA is a modular scaffold, allowing the integration of independent and interdependent functionalities onto one assembly. By harnessing the modularity of DNA, we continuously develop two halves of a universal in vivo chemical imaging platform. One halfdeals with creating "measuring modules" for specific analytes. It uses a DNA scaffold to display both (i) analyte detection chemistries and (ii) normalizing dyes to measure analyte concentration (1-3). The other half creates "targeting modules" for specific organelles. Here, organelle trafficking motifs are incorporated onto DNA nanodevices to enable their localization in a designated area of the cell (1). Together the two halves now allow one to measure analyte concentrations with accuracies that were previously unattainable in subcellular locations that were previously inaccessible.
