Acquisition of a calScreener Isothermal Microcalorimetry System for Translational Cancer Metabolism Research at Roswell Park - PROJECT SUMMARY / ABSTRACT Funds are requested to obtain a calScreener Isothermal Microcalorimetry System from Symcel at Roswell Park Comprehensive Cancer Center. This instrument is a label free, cell-based assay system based on measuring the heat flux/metabolism from living cells in real time and will provide unique value to investigators at Roswell Park, and the surrounding area in Western New York. This system is cost effective, and can be used for mammalian cells, bacteria, fungi, and parasites, in conventional cell culture, three-dimensional cultures, as well as tissue samples. It functions independent of media composition, making it applicable to many different types of projects. While there are tools for studying metabolism at Roswell Park (such as the Agilent Seahorse XFe96 Analyzer), there is no comparable technology to the calScreener. In fact, there are no comparable technologies available anywhere on the market, and the nearest calScreener is in Milwaukee, WI, over 600 miles away. Without this device, it would not be possible to investigate several important problems in cancer biology and immunology. For example, traditional metabolism technologies, cells must be isolated and evaluated at specific timepoints during an experiment. This instrument allows for continuous datacollection throughout an experiment, allowing for the quantification of metabolism over time. It also allows for the analysis of entire tissue sections without disrupting the architecture of the tissue. This allows investigators to study the effect of various treatments on the metabolic state of the tumor microenvironment including chemo-radiation therapy, immunotherapy, and metabolic inhibitors. Using these advantages, we can investigate the effects of inhibiting various metabolic pathways in T cells, myeloid cells, and tumor cells as described in our research projects. Additionally, while most researchers view heat production as merely an inert byproduct of metabolism, temperature flux is a major component of the function of cells that we can now study. Thus, this instrument will allow us to answer fundamental questions at the intersection of tumor biology, immunology, and thermobiology. The calScreener will be housed in the Immune Analysis Facility (IAF), where it will be closely supervised and available as a shared resource. There are 10 major users of the instrument that together will use ~80% of the instrument capacity. The remaining instrument capacity will be made available to internal or external researchers through our on -line scheduling and booking system. The IAF will generate a business plan, with a multidisciplinary advisory board responsible for instrument oversight, while the Cancer Center will support the instrument through service contracts, personnel, and marketing/promoting. Finally, this new instrument will not only provide unique data that will enable researchers to best advance their programs to obtain new grants and publications, but it will also provide a new dimension in pre-clinical and clinical applications that benefit cancer patients.
