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Abstract:
The primary function of DNA is the storage and transfer of biological information, but the past decade has seen a paradigm shift in terms of the molecular functions that can be achieved with engineered DNA-based constructs. For example, structures formed from DNA can generate sophisticated and dynamic “smart materials” or even 3D constructs (i.e. DNA origami) or can exhibit remarkably specific and strong recognition of molecular targets (i.e. aptamers). The path to advance DNA-based materials in biomedical applications is being approached carefully and systematically, starting from devising tools to inspect the stability and integrity of DNA nanostructures, to adding complex functions such as signaling and switching and estimating the accessibility and application of such devices inside model animal systems. In the first part of my talk, I will discuss how we generated complex reconfigurable DNA assemblies and specifically used single molecule fluorescence methodologies for the in-situ study of structure, dynamics, integrity, and operation of these DNA-based devices. The techniques we developed have the potential to significantly increase the quality of structural information obtained for DNA nanocarrier to use them as promising candidates for applications in smart/targeted delivery.
In the second part of my talk, I will highlight our recent work on the development of a real-time DNA-based biosensor technology that will enable the simultaneous detection of major neuromodulators (e.g. Dopamine and Serotonin) in the brain of living animals – in real time. Instead of relying on conventional electrochemical approaches, we are using structure-switching DNA aptamers that change their conformation upon binding to specific neuromodulators and optically measure the binding signal using optical waveguides and highly sensitive optical detection methods. The invention of optogenetics has transformed neuroscience by providing the technology to control the firing of specific neurons and the means to link neuronal activity to behavior in freely behaving animals. Similarly, we believe that our novel sensor will help create a “multi-dimensional map” of how different neural circuits, influenced by different neuromodulators, operate together to govern behavior and disease in a manner not previously achievable. Indeed, if successful, this technology will enable us to generate more biologically meaningful insights into the effects of drugs on brain function; and a have a better understanding of the pathophysiology of prominent brain disorders. This advanced optical biosensor platform can be generalized to detect pathogens, proteins and many biomarkers to provides valuable information about a given disease state.