SUMMIT · Site-specific Ultrasensitive Magnetic resonance of Mixtures for Isotopic Tracking

There is a high demand to design approaches capable of tracking the origin of biomarkers in complex biological environments, in the areas of life, environmental, food and forensic sciences. Metabolomics and Fluxomics show great promises towards this aim, and a high potential arises from their combination with Isotopic fingerprinting at natural abundance. The resulting isotopomics approach requires cutting-edge analytical tools, and Nuclear Magnetic Resonance (NMR) is currently the only generic technique giving access to the site-specific isotope content at natural abundance. The detection of very small relative variations between samples originating from different (bio)chemical pathways is possible through 13C isotopic NMR, which can however only be applied to simple and concentrated samples, due to its low sensitivity. Consequently, numerous applications are out of reach. To tackle the current limitations of 13C isotopic analysis, SUMMIT will develop a groundbreaking analytical workflow relying on two of the most powerful NMR methods: dissolution dynamic nuclear polarization and ultrafast 2D NMR. This cutting-edge approach will allow the simultaneous measurement of 13C fingerprints from multiple low-concentrated biomarkers in complex mixtures, which is impossible with existing methods. The high potential of this analytical strategy will be demonstrated on a relevant biological study, the investigation of breast cancer cell metabolism, through applications with gradually increasing risk levels. These approaches will make it possible to identify (i) new biomarkers to discriminate between cell lines expressing different hormonal receptors; (ii) novel potential therapeutic targets from the elucidation of metabolic pathways. Beyond this application, the project will have a high impact on a wide community of academic and industrial researchers, covering unmet needs from life sciences, food industry and forensic analysis.