Resource for Quantitative Elemental Mapping for the Life Sciences

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PROJECT SUMMARY – OVERALL Inorganic chemistry plays myriad, evolutionarily-conserved roles in physiology and pathology. Cells must accumulate several metals, such as zinc and iron, to millimolar levels in order to survive. They can deploy fluctuations in metal content to control processes as varied as the mammalian cell cycle, pathogen infection and neurological function. The critical regulatory role of metals is emphasized by the observation that one-third of all protein-encoding genes in the human genome encode metal-dependent proteins. There is an increasing appreciation in the NIH research community that intracellular content and subcellular location of each element provides an inorganic signature that serves as a quantitative phenotype. These realizations are driving the demand for new technologies for quantitative evaluation of inorganic signatures in cells and tissues. Such methods are essential to understanding the regulation of physiological and pathogenic processes and developmental decisions. The proposed Resource for Elemental Imaging for Life Sciences (QE-Map) will develop and integrate emerging technologies to create transformative approaches to the compelling biological question concerning inorganic chemistry in health and disease. The technologies to be developed comprise a suite of three imaging and detection methods that will allow investigators to quantitatively map the distribution of dozens of elements in samples ranging from cell extracts to fixed cells to tissue slices. The complementary and integrative nature of these methods is critical to enabling investigators to examine fluxes in intracellular ion content and localization, and to link these fluxes to changes in distribution within tissues and in living animals. A multi-disciplinary team, located at Northwestern University and Argonne National Laboratories, will address current limitations of LA-ICP-MS and SXFM technologies and will launch the development of photoacoustic methods and probes to enable studies at the tissue level. We will develop workflows and software that allows co-registration of images and standardization of quantitative data that will maximize the impact and accelerate application to a broad range of biomedical research. A portfolio of twelve DBPs was selected for their capacity to enable iterative development of new methods, and address high impact research questions in the field of “inorganic physiology.” The DBPs focus on 4 themes: (a) metal regulation in brain function and pathology; (b) metal modulation of host-pathogen interactions; (c) metal fluxes controlling reproduction and development; and (d) metal imbalances in metabolic pathology. A Community Engagement program will foster training of new technology users and dissemination of the technologies to the scientific community. The integration and coordination of Resource projects and activities will be enabled by the Administrative Core, co-directed by Drs. Thomas O’Halloran and Chris Jacobsen, and supported by an External Advisory Committee and an Executive Committee.