Description du projet
Spectrométrie de masse avancée pour la métabolomique du cancer
La métabolomique, incluant la lipidomique, apparaît comme une approche prometteuse pour fournir de nouvelles informations sur la régulation du métabolisme dans un contexte de santé et de maladie. La spectrométrie de masse constitue la technique de choix pour l’analyse des biomolécules telles que les peptides, les lipides et les sucres dans des échantillons biologiques. Les scientifiques du projet MASS2, financé par l’UE, entendent surmonter certaines limites de l’analyse des tissus complexes par le biais de la spectrométrie de masse. La technologie améliorée facilitera la caractérisation complète des tissus et sera accompagnée d’un logiciel spécialisé pour l’analyse de multiples paramètres. MASS2 se concentrera sur le suivi du cancer de la vessie pour en caractériser la physiologie et identifier de nouveaux biomarqueurs de pronostic et de diagnostic.
Objectif
Matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry imaging (MSI) is increasingly used for clinical application. Based on untargeted, spatial chemical information, tissue samples can be analysed with superior density of information compared to conventional histology techniques. However, MALDI suffers from several significant limitations like strong ion suppression effects, inherently low ion yields limited to a few classes of polar to mid-polar analytes, and impeded detection of low-weight compounds. This crucially hampers a comprehensive analysis of complex biological samples. Strategies for post ionisation (PI) – most prominently MALDI-2 – significantly increase the ion yields for numerous mid-polar and polar compounds. Surface-assisted LDI (SALDI) uses photoactive surfaces, which feature specific ablation and ionisation that can majorly extend the range of detectable compounds and can be prepared in a superiorly homogeneous manner for SALDI-MSI.
The proposed study aims to develop a novel means for extensive metabolome and lipidome analysis by SALDI-PI-MSI to overcome limitations of MALDI. Therefore, a new PI strategy coined Single-Photon Induced Chemical Ionisation (SPICI) will be combined with functionalised Au layers for comprehensive tissue characterisation of an extended polarity range with high mass resolution. The versatile software package rMSI will provides the computational means for the analysis of the complex measured data sets. We will apply our approach to human samples of bladder cancer tumour and achieve detailed monitoring of physiological processes in the cancerous tissue in unpreceded analytical depth. Newly identified biomarkers will help the urgent need for prognostic and diagnostic means for cancer. This comprehensive approach can be a massive generator of hypotheses for disease characterisation and foster the implementation of MSI into further fields of medical research and help to mature MSI in a multidisciplinary fashion.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinateur
43003 Tarragona
Espagne