A Nanomachine for Repair of Human DNA (RMI)

纳米医学的目标是在治疗疾病和修复损伤的分子干预中使用详细的分子机器知识。我们建议建立一个中心来剖析纳米机器的运作，该机器在人类细胞中执行主要的DNA修复过程。这一过程被称为核苷酸切除修复(NER)，它至少涉及25个蛋白质因子。获得的关于NER机械的知识将被用于纳米医学。在这份概念发展备忘录中，我们首先概述了进行与人类健康相关的NER纳米机器深入研究的令人信服的理由。我们确定了一些新出现的问题和现有知识中的差距。拟议的调查将首先由四个科学家工作组进行：生物化学、结构生物物理、高级测量和成像科学以及计算分子生物物理。每个小组都将围绕来自匹兹堡大学和桑迪亚国家实验室的科学家组成。匹兹堡大学的独特优势包括成像、计算生物学、生物化学和DNA单分子操作，而桑迪亚实验室尤其以生物分子材料和界面、化学合成和纳米材料以及微型传感器的科学和技术而闻名。这一批调查人员的共同努力，将形成新领域发展的强大力量 纳米医学。一个主要的目标是开发分析NER纳米机器的工具，这些工具可以用于研究与纳米医学相关的其他细胞机器。申请的资金将用于促进科学家和工程师之间的互动，以准备提交给NIH的概念开发计划，作为发展纳米医学中心的下一步。

The goal of nanomedicine is to use a detailed knowledge of molecular machines in molecular intervention for treating disease and repairing damage. We propose to establish a center to dissect the operation of a nanomachine that carries out a major DNA repair process in human cells. This process is called nucleotide excision repair (NER), and it involves at least 25 protein factors. The knowledge gained about the NER machinery will be harnessed for application to nanomedicine. In this Concept Development Memo we first outline compelling reasons for undertaking an intensive study of the NER nanomachine in relation to human health. We identify some emerging questions and gaps in existing knowledge. The proposed investigations will be carried out initially by four working groups of scientists: Biochemistry, Structural Biophysics, Advanced Measurement and Imaging Science, and Computational Molecular Biophysics. Each of these groups will be formed around a core of scientists drawn from the University of Pittsburgh and from Sandia National Laboratories. Particular strengths at the University of Pittsburgh include imaging, computational biology, biochemistry and single-molecule manipulation of DNA, while Sandia Labs is noted especially for strengths in biomoiecular materials and interfaces, chemical synthesis and nanomaterials, and the science and technology of microsensors. Together, this group of investigators will form a powerful force in development of the new field of nanomedicine. A major goal is to develop tools for analysis of the NER nanomachine that can be utilized to investigate other cellular machines relevant to nanomedicine. The requested funds will be used to facilitate the interactions of scientists and engineers in preparing a Concept Development Plan for submission to NIH as the next step in developing a Nanomedicine Center.