Integrated mass spectrometric methods for the analysis of protein function and proteome regulation

蛋白质构成了任何类型细胞的大部分成分。这个分子家族基本上也参与了所有的细胞过程或结构。了解细胞是如何工作的，即在任何时间点进行的许多不同任务是如何协调的，需要专门的分析工具。质谱法是一种功能强大、用途广泛的分析技术，可用于分析单个蛋白质及其所经历的修饰、它们之间的相互作用，也可用于分析细胞结构，甚至整个细胞、组织和生物体。我们的实验室专注于开发和实施新的质谱技术，可以在所有这些不同的水平上研究细胞。我们在创新方面有着良好的记录，例如我们在甲醛交联蛋白相互作用研究方面的开创性工作，以及我们在蛋白质修饰分析方面的多种方法。我们在跨学科环境中培养研究生方面有着良好的记录，这提高了他们的资格，并增加了他们成为高素质人才的机会。在本提案中，我们寻求资金继续培训研究生，他们将从事开发和优化专用的基于质谱和生物信息学的工具，用于分析单个蛋白质，它们的浓度，修饰状态，稳定性，相互作用以及它们对细胞中整个蛋白质含量（蛋白质组）的调节的影响。其中一些方法将整合到一个更全面的工作流程中，并应用于几个合作中的选定项目，重点关注哺乳动物和海洋生物学的各个方面。

Proteins make up the majority of the content of any type of cell. This family of molecules is also involved in essentially all cellular processes or structures. Understanding how cells work, i.e. how the many different tasks that are being carried out at any point in time are coordinated, requires dedicated analytical tools. Mass spectrometry is a powerful and versatile analytical technique that can be employed for the analysis of individual proteins and modifications they undergo, their interactions, but also of cellular structures, and even entire cells, tissues, and organisms. Our laboratory focuses on the development and implementation of novel mass spectrometric techniques that allow to study cells at all of these different levels. We have a strong track record of innovation, such as our pioneering work on formaldehyde cross-linking for protein interaction studies and our multiplex approaches for protein modification analysis. We have an excellent track record in the training of graduate students in an interdisciplinary environment, which enhances their qualifications and improves their chances for subsequent employment as highly qualified personnel. In this proposal, we seek funding to continue the training of graduate students who will engage in the development and optimization of dedicated mass spectrometry-based and bioinformatic tools for the analysis of individual proteins, their concentration, modification state, stability, interactions, as well as their impact on the regulation of the entire protein content of the cell (the proteome). Several of these methods will be integrated into a more comprehensive workflow, and applied to selected projects in several collaborations, focusing on aspects of mammalian and marine biology.