Descrizione del progetto
Un approccio inedito per migliorare il rilevamento delle impronte tramite biomarcatori
Il tracciamento dell’origine del biomarcatore si dimostra sempre più fondamentale in molti ambiti differenti, quali le scienze della vita, dell’ambiente, dell’alimentazione e la scienza forense. La combinazione di metabolomica e flussomica con il rilevamento delle impronte isotopiche mostra grandi potenzialità per il raggiungimento di tale obiettivo. L’analisi isotopica tramite risonanza magnetica nucleare (RMN) permette agli scienziati di quantificare con notevole precisione le differenze tra indici isotopici su ogni sito di una molecola. Il progetto SUMMIT, finanziato dall’UE, è stato istituito per intervenire sugli attuali limiti dell’analisi RMN di isotopi del carbonio-13. Avvalendosi di due potenti metodi di RMN, ovvero la polarizzazione nucleare dinamica di dissoluzione e la risonanza magnetica nucleare bidimensionale ultra rapida, il progetto consentirà agli scienziati la misurazione simultanea di impronte di carbonio-13 da molteplici biomarcatori a bassa concentrazione presenti in miscele biologiche complesse, un compito arduo da svolgere mediante i metodi esistenti.
Obiettivo
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.
Campo scientifico
Not validated
Not validated
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
44000 Nantes
Francia