Advances in imaging mass spectrometry

成像质谱学(MS)是一项新兴技术，它允许在一次实验中绘制出组织切片中存在的数百种不同化合物的图谱。多种类型的生物化合物，包括代谢物、磷脂、多肽和蛋白质，可以被检测到，并与潜在的组织学直接相关地成像。分子图谱和图像是特定于细胞和组织的，它们的一些特征可以直接与组织样本的健康状况相关。事实上，这项技术足够灵敏，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L的蒙特雷亚尔大学化学系实施并进一步开发这种基于质谱学的技术。将开展两个主轴的研究：1)开发和优化福尔马林固定石蜡包埋(FFPE)组织标本的成像MS分析方案；2)利用串联耗尽策略通过成像MS分析冷冻组织标本中特定的蛋白质组亚群，并引入蛋白质浓缩表面化学。通过这些发展所获得的知识的总和将使我们能够在保持空间组织的同时，以更深层次的敏感性来查询组织的蛋白质组内容。总而言之，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.