CAREER: Bioinformatics of Protein Post-Translational Modifications

职业：蛋白质翻译后修饰的生物信息学

• 批准号: 0644017
• 负责人: Predrag Radivojac
• 金额: $ 59.59万
• 依托单位: Indiana 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: 2007-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0644017&HistoricalAwards=false
• 关键词: CAREER; Bioinformatics; Protein; Post; Translational

Indiana University is given a CAREER award for Predrag Radivojac to develop new methods to study protein post-translational modifications (PTMs), i.e. covalent modifications to protein structure after its translation. It is now known that there are over 200 PTM types that modulate protein activity in eukaryotic organisms by acting as molecular switches which turn on and off protein function, stabilize it or target for destruction or determine its cellular location. The objective is to carry out the following research activities: (Aim 1) Develop models for automated annotation of PTM sites (Aim 2) Analyze structural and functional properties of PTM sites (Aim 3) Integrate protein bioinformatics and proteomics to construct functional map of all major PTMs Intellectual Merit. This project introduces a novel framework of integrating protein bioinformatics and proteomics towards comprehensive understanding of the regulatory and signaling roles of PTMs. In addition to the new biological knowledge, this project will develop a set of tools that will enable accurate and efficient proteomics analysis and also aid experimental biologists in experimental design. Combinatorial explosion is currently the major hindrance in proteomics studies of PTMs and cellular processes they are involved in. Thus, the proposed prioritization of the proteomics searches by incorporating PTM prediction will not only make such studies realistic, but also enable identification of many new sites by decreasing the effective database size. PTMs frequently occur in unstructured protein regions that cannot be easily studied using traditional experimental methods (X-ray crystallography, NMR spectroscopy) and structural bioinformatics. Developing sequence based methods to predict PTM sites, integrating them into proteomics searches for verification, and investigating relationship between PTMs and genetic data may be crucial for understanding the molecular basis of many diseases, thus facilitating drug design and clinical therapy. The far-reaching promise of understanding life at a molecular level and advancing medical research can be fulfilled only through an integration of research and interdisciplinary education. To achieve this goal, the PI will extend and develop new courses at graduate and undergraduate level, will expose students to advanced education, and, through an active, rigorous and enthusiastic learning environment; train a generation of new experts and researchers who will be capable of making further advances. The teaching material and research results will be disseminated via our web site, by publishing papers in internationally recognized journals and by attending major conferences. The educational plan of this project will ensure participation of underrepresented minority and socioeconomic groups in research by partnering with the Office of Strategic Mentoring (OSM) and Alliances for Graduate and Professoriate Program (AGEP) at Indiana University. Two vital components of this plan are (i) attracting underrepresented students through OSM/AGEP and courses addressing data mining and bioinformatics, and (ii) retaining and promoting underrepresented students through committing funding, advising and mentoring.

印第安纳大学因 Predrag Radivojac 开发研究蛋白质翻译后修饰 (PTM) 的新方法而获得职业奖，即蛋白质翻译后结构的共价修饰。目前已知有超过 200 种 PTM 类型可通过充当分子开关来调节真核生物中的蛋白质活性，这些分子开关可打开和关闭蛋白质功能、稳定蛋白质或靶向破坏或确定其细胞位置。目标是开展以下研究活动：（目标 1）开发 PTM 位点自动注释模型（目标 2）分析 PTM 位点的结构和功能特性（目标 3）整合蛋白质生物信息学和蛋白质组学，构建所有蛋白质的功能图谱主要 PTM 智力优点。该项目引入了一个整合蛋白质生物信息学和蛋白质组学的新框架，以全面了解 PTM 的调控和信号传导作用。除了新的生物学知识外，该项目还将开发一套工具，以实现准确、高效的蛋白质组学分析，并帮助实验生物学家进行实验设计。组合爆炸是目前 PTM 及其参与的细胞过程的蛋白质组学研究的主要障碍。因此，通过结合 PTM 预测对蛋白质组学搜索进行优先排序不仅将使此类研究变得现实，而且还能够通过以下方法识别许多新位点：减少有效数据库大小。 PTM 经常出现在非结构化蛋白质区域中，使用传统实验方法（X 射线晶体学、核磁共振波谱）和结构生物信息学无法轻松研究这些区域。开发基于序列的方法来预测 PTM 位点，将其整合到蛋白质组学搜索中进行验证，以及研究 PTM 与遗传数据之间的关系对于了解许多疾病的分子基础，从而促进药物设计和临床治疗至关重要。只有通过研究和跨学科教育的结合，才能实现在分子水平上理解生命和推进医学研究的深远承诺。为了实现这一目标，PI将在研究生和本科阶段扩展和开发新课程，让学生接受先进的教育，并通过积极、严谨和热情的学习环境；培养一代能够取得进一步进步的新专家和研究人员。教材和研究成果将通过我们的网站、在国际公认的期刊上发表论文以及参加主要会议来传播。该项目的教育计划将通过与印第安纳大学战略指导办公室 (OSM) 和研究生和教授计划联盟 (AGEP) 合作，确保代表性不足的少数群体和社会经济群体参与研究。该计划的两个重要组成部分是（i）通过 OSM/AGEP 以及涉及数据挖掘和生物信息学的课程吸引代表性不足的学生，以及（ii）通过承诺资助、建议和指导来保留和促进代表性不足的学生。