A Nanomachine for Repair of Human DNA (RMI)

纳米医学的目标是利用分子机器的详细知识在分子干预中治疗疾病和修复损伤。我们建议建立一个中心来解剖在人类细胞中进行主要DNA修复过程的纳米机器的操作。这个过程被称为核苷酸切除修复（NER），它涉及至少25个蛋白质因子。获得的关于NER机制的知识将用于纳米医学的应用。在这一概念发展备忘录中，我们首先概述了开展与人类健康有关的NER纳米机器深入研究的令人信服的理由。我们在现有知识中发现了一些新出现的问题和差距。拟议的研究最初将由四个科学家工作组进行：生物化学、结构生物物理学、高级测量和成像科学以及计算分子生物物理学。每一个小组都将由来自匹兹堡大学和桑迪亚国家实验室的核心科学家组成。匹兹堡大学的优势包括成像、计算生物学、生物化学和DNA单分子操作，而桑迪亚实验室则以生物分子材料和界面、化学合成和纳米材料以及微传感器科学和技术的优势而闻名。这群研究人员将共同形成发展新领域的强大力量

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.