A super-resolution microscope for visualizing cellular structure and dynamics

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Well below the resolution limit dictated by the wavelength of light, super-resolution confocal microscopes bend the laws of physics to allow cell and developmental biologist to peer down at molecular machines at work within living cells. This Nobel prize winning advance in microscopy is quickly becoming the standard for all high-impact molecular cell biology research, including that conducted by all the member labs of the Centre for Cell Biology, Development and Disease (C2D2) at Simon Fraser University (SFU). In addition to the need for this new super-resolution technology, we are also desperate for another multi-purpose confocal microscope. There currently exists only two confocal microscopes at SFU (for the entire campus) that are generally available to the >183 faculty and student users. Apart from being oversubscribed, these confocal microscopes are aging systems that are reaching the end of their functionality. We propose to acquire a base model super-resolution confocal microscope that offers flexibility to serve both the routine microscopy needs of all SFU researchers but also to provide our institution with its first super-resolution microscope. The TCS SP8 microscope with Hyvolution from Leica can provide tremendous benefits not fulfilled by our current confocal microscopes, namely, a combination of high sensitivity, speed, excellent depth of penetration for any sample, and most importantly, resolving power that is significantly higher. Overwhelming support for the acquisition of this system is underscored by the many pledged contributions, which are needed in addition to the NSERC RTI to purchase the equipment, coming from three SFU Departments (MBB, BISC, BPK), two Faculties (Science, Health Sciences), and a number of individual researchers (the lead applicant Dr. C. Beh and 10 other investigators from across SFU). The added benefit of the proposed system is that it is modular, permitting future upgrades to the base system for even higher resolution capabilities. The flexibility of the proposed microscope system matches the varied NSERC-funded research activities of the molecular cell biology labs at SFU. As the lead applicant, the Beh lab will use the super-resolution microscope to directly visualize the tiny contact sites between internal cellular membranes to understand how these sites mediate the transport of lipids and metabolites back-and-forth. The 10 co-applicants (Drs. T. Beischlag, S. Gorski, N. Harden, N. Hawkins, H. Hutter, M. Moore, G. Rintoul, M. Silverman, G. Tibbits, and D. Vocadlo) will apply the new equipment to various research interests ranging from nerve cell transport and cellular process regulating organ development, to cellular etiologies of cancer and the tracking of intracellular pathogens. As an open resource to all SFU users, trained students will benefit from the mastery of this technologically advanced system for future employment in biotech.