Collaborative Research: Arabidopsis 2010: Function/Structure Annotation of Lipid Binding Domains in Arabidopsis Thaliana Proteins: Computational Modeling of Subcellular Targeting

合作研究：拟南芥 2010：拟南芥蛋白质脂质结合域的功能/结构注释：亚细胞靶向的计算模型

• 批准号: 0738311
• 负责人: Diana Murray
• 金额: $ 95.05万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0738311&HistoricalAwards=false
• 关键词: Collaborative; Research; Arabidopsis; 2010; Function

The reversible binding of proteins to cellular membranes is central to many biological processes and is often accomplished through lipid-interacting protein domains. The Arabidopsis genome contains at least 2,000 such domains. Different types of lipid signals target the domains to different cellular membranes. The interaction of lipid-binding domains with membrane surfaces is an essential part of their function. This project aims to understand, at the molecular level, how these domains are recruited to different cellular membranes and how proteins and lipid signals are organized laterally at membrane surfaces and, thus, regulate cellular processes. Function will be determined at the family and genome levels through the synthesis of computational and experimental analyses. An automated high-throughput comparative modeling pipeline will detect new instances of lipid-binding domains in the Arabidopsis genome and predict the structures of their amino acid sequences using known structures as templates. The biophysical properties of these models will be calculated and the functional predictions will be tested through the interpretation and rational design of experiments. Ultimately, detailed models of the physical interactions underlying lipid signaling pathways at membrane surfaces will be built in collaboration with experiment. This project reflects all three of the current 2010 Project focus activities: 1) Benchmarking gene function. Genes from Arabidopsis will be quantitatively compared with genes from other, much more annotated model organisms. 2) Developing genome-wide tools for analyzing gene function: The comparative modeling pipeline, which is highly modular, is the framework for a comprehensive tool that allows for the inclusion of new computational methods to facilitate both larger scale and more detailed annotation of gene function. 3) Exploring exemplary networks and systems: The results for individual lipid-binding domains will be leveraged to model how proteins and lipids collaborate to transduce cellular signaling. Finally, an automated mechanism for alerting other 2010 Program groups to potentially useful results will be implemented. Information on this project is posted at http://maat.med.cornell.edu/Arabidopsis2010/arabidopsis2010.html.The foundation of this effort is a strong partnership between Weill Medical College of Cornell University (WMC) and City University of New York Brooklyn College (CB), which is a non-PhD granting institution. The values of this partnership are research, education, mentoring, and outreach activities. Through this project, two early career female scientists, one of which has two children, will receive training in new areas of biology and computation and, together, will develop a supportive research environment for women through this project as well as other areas of research. Both labs mentor many young women at all levels of education, from high school through the postdoctoral level. There is strong multidisciplinary and multiethnic student participation: Two minority female high school students were finalists in the International Intel Competition, and another minority female high school student is currently working on an Intel project. Undergraduate and graduate students at CB and WMC are being trained in computational biology by participating in this project and through formal course work. Both investigators design and teach classes in Bioinformatics, Computational Biology, Biochemistry, Logic and Critical Analysis, and journal-based "Focus Groups". The results of this project will be broadly disseminated through 1) a dedicated, publicly accessible, database-driven website with links to online Arabidopsis resources; 2) participation in multi-disciplinary conferences and Arabidopsis-specific data-support services; 3) publications in quality, multidisciplinary journals, e.g. PLoS Computational Biology, which seeks to make computation accessible to biologists; and 4) seminars presented to "Women in Science" programs and programs meant to recruit students from other fields into biology, e.g. American Physical Society Biology Tutorials. It is anticipated that a highly successful, eight-session, 48-speaker symposium on protein/membrane interactions, organized by one of the investigators for the American Chemical Society March 2006 meeting, is the first in a series of similar meetings that will bring together experimental and computational researchers in this field. Future meetings will have sessions devoted to Arabidopsis membrane binding proteins.

蛋白质与细胞膜的可逆结合是许多生物过程的核心，通常是通过脂类相互作用的蛋白质结构域来完成的。拟南芥基因组包含至少2000个这样的结构域。不同类型的脂质信号将这些结构域指向不同的细胞膜。脂质结合域与膜表面的相互作用是其功能的重要组成部分。这个项目的目的是在分子水平上了解这些结构域如何被招募到不同的细胞膜上，以及蛋白质和脂肪信号如何在膜表面横向组织，从而调节细胞过程。功能将通过计算和实验分析的综合，在家族和基因组层面上确定。一个自动化的高通量比较建模管道将检测拟南芥基因组中脂结合结构域的新实例，并使用已知结构作为模板预测其氨基酸序列的结构。这些模型的生物物理性质将通过实验的解释和合理设计来计算和验证功能预测。最终，将与实验合作建立膜表面脂质信号通路下的物理相互作用的详细模型。该项目反映了目前2010年项目的所有三项重点活动：1)确定基因功能的基准。来自拟南芥的基因将与其他更具注解的模式生物的基因进行定量比较。2)开发全基因组范围的基因功能分析工具：高度模块化的比较建模管道是一个综合工具的框架，该工具允许包括新的计算方法，以促进对基因功能的更大规模和更详细的注释。3)探索示范网络和系统：单个脂结合结构域的结果将被用来模拟蛋白质和脂类如何协作传递细胞信号。最后，将实施一个自动机制，提醒其他2010年方案组注意可能有用的成果。有关该项目的信息发布在http://maat.med.cornell.edu/Arabidopsis2010/arabidopsis2010.html.The网站上，这项工作的基础是康奈尔大学威尔医学院和纽约城市大学布鲁克林学院(CB)之间的牢固合作伙伴关系，后者是一家非授予博士学位的机构。这种伙伴关系的价值在于研究、教育、指导和外展活动。通过这一项目，两名职业生涯早期的女科学家，其中一人有两个孩子，将接受生物学和计算新领域的培训，并将通过这一项目以及其他研究领域，共同为妇女建立一个支持性的研究环境。这两个实验室指导了从高中到博士后水平的各种教育水平的年轻女性。有很强的多学科和多种族学生参与：两名少数族裔女高中生进入了国际英特尔竞赛的决赛，另一名少数族裔女高中生目前正在参与一个英特尔项目。CB和WMC的本科生和研究生正在通过参与这一项目和通过正式的课程工作接受计算生物学方面的培训。两位研究人员都设计和教授生物信息学、计算生物学、生物化学、逻辑和关键分析课程，以及以期刊为基础的“焦点小组”。该项目的成果将通过以下方式广泛传播：1)一个专门的、公众可访问的、由数据库驱动的网站，带有与在线拟南芥资源的链接；2)参加多学科会议和特定于拟南芥的数据支持服务；3)在高质量的多学科期刊上发表文章，如PLoS计算生物学，其目的是使生物学家能够获得计算；和4)为“女性参与科学”计划和计划举办研讨会，这些计划旨在招募来自其他领域的学生进入生物学领域，如美国物理学会生物学教程。预计，由美国化学学会2006年3月会议的一名研究人员组织的关于蛋白质/膜相互作用的非常成功的八节48人专题讨论会将是一系列类似会议中的第一次，这些会议将聚集这一领域的实验和计算研究人员。未来的会议将专门讨论拟南芥的膜结合蛋白。