High-Throughput Technology for Global Protein and Metabolite Analysis

 描述(申请人提供)：人类基因组测序标志着理解复杂生物体的集体科学考察的开始。当然，基因只包含蛋白质将填充到细胞中的指令。解开调控复杂生物体及其疾病的多方面网络将需要创新技术来全球监测许多类别的生物分子，包括核酸、蛋白质和代谢物。高通量的基因和转录本测量技术已经发展得很好，而且可以广泛获得，因此对现代生物学和医学产生了奇妙的和变革性的影响。由于许多原因，对蛋白质和代谢物--关键的生物效应分子--进行全球分析的方法进化得较少，而且明显更难获得。我的计划的首要任务是(1)通过创新新的质谱学技术来促进对蛋白质和代谢物的便捷、全面的分析，以及(2)将这些技术应用于推进生物医学研究。为了实现这些目标，我们的努力集中在四个主要领域：仪器和信息学、蛋白质组学方法论、代谢组学和生物医学应用。首先，利用我们广泛的电子转移解离(ETD)开发历史，我们计划扩大我们的能力，以询问许多目前难以处理的多肽、翻译后修饰(PTM)和其他生物分子。其次，有了这些和其他工具，我们将简化和加快蛋白质组分析；我们设想在几小时甚至几分钟内分析整个蛋白质组(&gt；10,000个蛋白质)或PTMome(&gt；10,000个磷酸化位点)。第三，通过开发新的化学仪器和软件工具，我们将推动代谢物分析和发现领域的发展。最后，上述技术是在相关生物学的背景下开发的，因此，我们计划将我们的创新工具应用于许多尖端生物医学项目。

 DESCRIPTION (provided by applicant): The sequencing of the human genome marked the beginning of a collective scientific expedition to understand complex organisms. Genes, of course, merely contain the instructions for which proteins will populate the cell. Untangling the multi-faceted networks that regulate complex organisms and their diseases will require innovative technologies to globally monitor many classes of biomolecules, including nucleic acids, proteins, and metabolites. High-throughput technologies for gene and transcript measurement are well-developed and broadly accessible, and, as such, have had a fantastic and transformative impact on modern biology and medicine. For numerous reasons, methods for global analysis of proteins and metabolites - crucial biological effector molecules - are less evolved and markedly less accessible. The overarching mission of my program is to (1) facilitate expedient, comprehensive analysis of proteins and metabolites by innovating new mass spectrometric technologies and (2) apply these techniques to advance biomedical research. To accomplish these goals we center our efforts on four main areas: Instrumentation and Informatics, Proteomic Methodology, Metabolomics, and Biomedical Applications. First, leveraging our extensive electron transfer dissociation (ETD) development history, we plan to expand our ability to interrogate many currently intractable peptides, post-translational modification (PTMs), and other biomolecules. Second, with these and other tools, we will simplify and expedite proteome analysis; we envision analyzing an entire proteome (>10,000 proteins) or PTMome (>10,000 phosphorylation sites) in hours, or even minutes. Third, by development of novel chemical instrumentation and software tools, we will advance the field of metabolite profiling and discovery. Finally, the above mentioned technologies are most meaningfully developed in the context of relevant biology and, therefore, we plan to apply our innovative tools to many cutting-edge biomedical projects.