Core--PROTEOMICS

蛋白质组学核心将针对与衰老系统中蛋白质结构相关的病理过程。重点将放在使用基于质谱的技术和化学方法来鉴定翻译后蛋白质修饰，如磷酸化或氧化修饰，这些修饰似乎在衰老和与年龄相关的疾病中起重要作用。核心还将开展涉及高通量蛋白质鉴定和蛋白质表达变化的实验，并定义复杂生物系统中蛋白质-蛋白质相互作用网络。这些活动将扩大巴克研究所作为蛋白质组学区域专门知识中心的作用，特别是在翻译后修饰和蛋白质-蛋白质复合物的应用方面。Core已经开发了新的方法来确定整个细胞器的蛋白质组（例如，线粒体），蛋白质磷酸化，半胱氨酸氧化还原状态，以及使用化学交联策略的蛋白质结构变化（MS3D）。

The Proteomics Core will target pathological processes associated with protein structures in aging systems. The emphasis will be on using mass spectrometry-based technologies and chemical methods to identify posttranslational protein modifications, such as phosphorylation or oxidative modification, which appear to play important roles in aging and age-related diseases. The Core will also carry out experiments involving high-throughput protein identification and protein expression changes, and defining protein-protein interaction networks in complex biological systems. These activities will extend the Buck Institute's role as a regional center of expertise in proteomics, particularly in applications to posttranslational modifications and protein-protein complexes. New methods have been developed by the Core for determining the proteomes of whole organelles (e.g., mitochondria), protein phosphorylation, cysteine redox status, and changes in protein structure using chemical crosslinking strategies (MS3D). The continued development and application of these methodologies will further enhance the Buck Institute's ability to serve as a regional or national resource for proteomics in aging systems. A key feature of our proposal is the exploitation of a new quadrupole linear ion trap mass spectrometer for these proteomic applications. The 4000 QTRAP hybrid triple quadrupole-linear ion trap instrument will provide high sensitivity, enhanced resolution scanning and enhanced product ion scanning when operated in the linear ion trap mode, while also retaining all conventional triple quadrupole scanning modes, such as multiple reaction monitoring, neutral loss and precursor ion scanning. Together with existing resources and staff at the Institute, the proposed 'Proteomics in Aging Facility' will greatly enhance our efforts at detailing the molecular events in the proteome that underlie the complex aging process in cells, tissues and organisms, as well as for age-related diseases, such as Alzheimer's disease.