Combinatorial Microscopies: Platforms for Probing Molecular and Cellular Dynamics and Structures

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Understanding and ultimately controlling how molecules assemble into functional structures is critical in fields ranging from materials science and chemistry to structural and cell biology. Determining the structural and conformational requirements for these complex assembly processes, and the dynamics thereof, is best accomplished by examining these phenomena on relevant length scales, in real-time, and under nominally real-world conditions. Our research focuses on the design and optimization of combinatorial microscopies, tools that integrate different imaging modalities into a common framework, in order to enable direct interrogation of molecular and cellular self-assembly. Our most recent work has, for instance, allowed us to map the distribution and association state of membrane receptors, located on the cell surface, with single-molecule resolution, and track developmental processes in real-time at the resolution of individual cells. Building on these innovations, we now propose to develop platforms that will allow us to track these phenomena throughout the cell, and importantly between cells. Such insights are critical for understanding how molecules are transported to the cell surface, their state and structure during transport, and what interactions drive these dynamic processes. Developing tools that allow us to track these processes and then subsequent inter-cellular interactions between associating cells will provide researchers with a powerful suite of approaches for understanding how signalling occurs between cells and the functional consequences of these events. This highly interdisciplinary research program embraces photonics, biophysics, chemistry, computer science, cell and molecular biology, and engineering. It draws in HQP from all levels (undergraduate, graduate, post-doctoral) from diverse backgrounds into a high collaborative and interdisciplinary research environment. Due to our emphasis on bespoke design, HQP are heavily involved in collaborations, both locally and globally, which provides a rich environment for innovation and creativity. HQP are directly involved in the design, optimization, implementation, and modification of unique and innovative imaging platforms, with a specific focus on open hardware and software design. By being fully involved in the application of these imaging platforms to complex biological questions and phenomena, HQP are not simply "using" black box imaging strategies but are afforded a unique and powerful opportunity to be fully engaged in all aspects of the research. The highly applied nature of our research efforts and the close collaborations with end-users and manufacturers as well as the open distribution of our protocols, plans, and code positions HQP from our lab for a diverse suite of careers, ranging from scientists in start-up companies to academic positions and business development professionals.