Advances in imaging mass spectrometry

成像质谱（MS）是一种新兴技术，其允许在单个实验中映射组织切片内存在的数百种不同化合物。许多类型的生物化合物，包括代谢物，磷脂，肽和蛋白质，可以检测和成像与潜在的组织学直接相关。分子谱和图像是细胞和组织特异性的，并且它们的一些特征可以与组织样本的健康状态直接相关。事实上，该技术足够敏感，可以检测到由于疾病的存在而导致的分子组成的细微变化。在接下来的五年里，我建议在蒙特利尔大学化学系实施并进一步发展这种基于质谱的技术。将开发两个主要研究轴：1）通过成像MS分析福尔马林固定石蜡包埋（FFPE）组织标本的方案的开发和优化;以及2）通过成像MS使用系列耗尽策略和引入蛋白富集表面化学分析冷冻组织标本的蛋白质组的特定亚群。通过这些发展获得的知识的总和将使我们能够以更深层次的灵敏度查询组织的蛋白质组内容，同时保持空间组织。总之，这些工具有望促进生物学和医学的新发现。

Imaging mass spectrometry (MS) is an emerging technology that allows to map in a single experiment hundreds of different compounds present within a tissue section. Numerous types of biocompounds including metabolites, phospholipids, peptides and proteins can be detected and imaged in direct correlation with the underlying histology. The molecular profiles and images are cells and tissue specific and some of their features can be directly correlated with the health status of a tissue specimen. Indeed, the technology is sensitive enough to detect subtle changes in molecular composition due to the presence of disease. Over the next five years, I propose to implement and further develop this mass spectrometry-based technology in the Department of Chemistry at l'Université de Montréal. Two main axis of research will be developed: 1) the development and optimization of protocols for the analysis of formalin fixed paraffin embedded (FFPE) tissue specimens by imaging MS; and 2) the analysis of specific subpopulations of the proteome from frozen tissue specimens by imaging MS using serial depletion strategies, and introducing protein enrichment surface chemistries. The sum of knowledge gained by these developments will allow us to query the proteomic content of tissues with a deeper level of sensitivity, while maintaining spatial organization. Together, these tools promise to promote new discoveries in biology and medicine.