AUTOMATION OF STEPS IN LARGE-SCALE DNA SEQUENCING

大规模 DNA 测序步骤的自动化

• 批准号: 3068608
• 负责人: Deirdre R. Meldrum
• 金额: $ 8.75万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3068608
• 关键词: bioengineering /biomedical engineering; biomedical automation; biomedical equipment development; biotechnology; method development; nucleic acid sequence; robotics

The overall objective of this research career award is to develop new methods and tools for automated large-scale DNA sequencing. Initially, the specific aims of the award are to: Train extensively in the field of genomics via lab rotations, courses and seminars in the Department of Molecular Biotechnology. In the lab training the candidate will perform all steps of DNA sequencing via current methods. This experience combined with the candidate's electrical engineering background will be used to develop fast, efficient methods to automate certain steps in large-scale DNA sequencing procedures. Develop a prototype robot that will dispense sub-microliter to sub- nanoliter volumes of reagents for DNA sequencing reactions. A precise robotic positioning system will be designed and built to access individual wells on 384-well or 864-well microtiter plates and alternate denser formats. Investigate and develop a new, automated procedure for loading sequencing reactions onto gels from high density formats. Currently this step in large-scale DNA sequencing is performed manually but with higher density reactions this will be more problematic. Explore alternate electrophoretic formats that require no net migration. Signal processing and identification techniques will be employed to identify DNA molecules in free solution. While performing the steps of large-scale DNA sequencing in lab training during the first year of the five year SERCA program, bottlenecks in large-scale DNA sequencing procedures will be identified. The remainder of the award will be used to focus on solving these problems using new, automated techniques. Ultimately, these technological developments will increase the throughput in DNA sequencing and contribute to the sequencing of the Human Genome. Deirdre Meldrum, the candidate, received her Ph.D. in Electrical Engineering from Stanford University in 1992. At Stanford and the Jet Propulsion Laboratory, Deirdre worked extensively on robotic and controls for space structures, space robots, and computer disk drives. Her strong background in robotics, controls, dynamics, and electrical/mechanical design will be invaluable for fulfilling the goal of automating steps in large-scale DNA sequencing. Throughout the award period and beyond, Deirdre will train and work closely with the faculty in the Department of Molecular Biology while maintaining close ties with the Department of Electrical Engineering. Leroy Hood, the principle faculty advisor, is Professor and Chair of the Department of Molecular Biotechnology at the University of Washington.

这一研究事业奖的总体目标是开发新的 自动化大规模DNA测序的方法和工具。最初， 该奖项的具体目的是： 通过实验室轮换、课程和 分子生物技术系的研讨会。在实验室里 培训候选人将通过以下途径执行DNA测序的所有步骤 目前的方法。这一经历与候选人的 将利用电气工程背景快速、高效地发展 大规模DNA测序中某些步骤的自动化方法 程序。 开发一种原型机器人，将亚微升分配到亚微升 用于DNA测序反应的纳升体积试剂。一个精准的 机器人定位系统将被设计和建造以访问 在384孔或864孔微滴定板上的单个井和 替代密度更高的格式。 研究和开发一种新的自动加载测序程序 在高密度格式的凝胶上发生反应。目前这一步是在 大规模DNA测序是手动执行的，但密度更高 反应这将是一个更大的问题。 探索不需要净迁移的替代电泳格式。 将使用信号处理和识别技术来 识别自由溶液中的DNA分子。 在实验室培训中执行大规模DNA测序的步骤 在五年SERCA计划的第一年， 将确定大规模的DNA测序程序。剩下的 将用于集中解决这些问题，使用新的， 自动化技术。最终，这些技术发展将 提高DNA测序的吞吐量，并为 人类基因组的测序。 候选人迪尔德丽·梅尔德鲁姆获得了电学博士学位 1992年从斯坦福大学获得工程学学位。在斯坦福大学和Jet Deirdre推进实验室在机器人和控制方面做了大量工作 用于空间结构、空间机器人和计算机磁盘驱动器。她的坚强 具有机器人、控制、动力学和电子/机械方面的背景 设计对于实现以下步骤的自动化目标将是无价的 大规模DNA测序。在整个颁奖期间和以后， Deirdre将与系内教职员工密切合作并进行培训 与分子生物学系保持密切联系 电气工程专业。首席教职顾问勒罗伊·胡德是 斯坦福大学分子生物技术系主任兼教授 华盛顿大学。