MRI: Acquisition of Aquilos Dual-Beam Microscope

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An award is made to the University of California San Diego to support the acquisition of a cryo-dual beam microscope to enable the three dimensional visualization of cells at the level of the structure of individual biomolecules. This technology will enable the development of completely novel hypothesis on how molecules perform their function within the molecular landscapes that they operate in. This project will realize this potential for laboratories at UC San Diego, and will extend the training opportunities from technically trained scientists to non-expert users, effectively democratizing this technology and training the next generation of instrumentalists from diverse backgrounds. Furthermore, the molecular landscapes that this project will reveal are great teaching and dissemination tools for general audiences, including the creation and circulation of virtual reality and videos that allow users to navigate and explore cellular territories from within. The acquisition of this instrument will support research projects that aim to observe intricate molecular networks in their natural environment. The scientific projects it will support span from technical projects that aim to develop new methodologies that will leverage the use of cryo-FIB milling for structural cell biology, to biologically driven projects with goals of unveiling the molecular mechanisms that result from specialized molecular networks in various model systems in cell biology. Method-related projects include development of novel computational algorithms to identify proteins within the molecular panoramas and enabling simulations of entire cells to predict cellular behavior under a variety of perturbations. Biologically driven projects include: unveiling unexplored mechanisms in bacterial cell biology, such as how bacterial cells divide and differentiate, how they respond to viral infection or keep track of time; the study of fundamental processes in the nucleus of eukaryotic cells such as how the genome organizes in 3-D and how this architecture determines the state of the cell. Together with future projects that will be enabled by this technology, the awarded project has the potential to make transformative discoveries that will unleash yet-unimagined hypothesis of cellular mechanisms in a wide range of biological scenarios.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.