权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Toward the molecular unpacking of the PaaC domain, a novel Plasmodesmata-association & activation Cassette

PaaC 结构域的分子解包，一种新型的胞连丝关联

基本信息

批准号：
1820103
负责人：
Jung-Youn Lee
金额：
$ 80万
依托单位：
University of Delaware
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1820103&HistoricalAwards=false
关键词：
Toward molecular unpacking PaaC domain

项目摘要

Many human diseases and developmental defects are associated with malfunction in communication between cells. Similarly, plants also suffer from uncontrolled spread of diseases, inappropriate seasonal or environmental responses, or improper organ development when cell-to-cell communication goes unchecked. This research, building on unique expertise in cell and molecular biology and computational modeling and machine learning, aims to unravel how important protein regulators are targeted to the channels that connect neighboring cells and fine tune cell communications in plants. New concepts and discoveries made by this research will be introduced to both graduate and undergraduate students as integrated new bioinformatics courses as well as laboratory modules. Furthermore, the software developed from this project will be made available free online to the public together with the source code. In addition, the newly produced data, results, and tools will be incorporated into an existing webserver with user-friendly interface to better serve the research and education community. The fundamental knowledge gained by this study has the potential to be utilized in the long run to engineer genetically encoded synthetic proteins to effectively control nutrient distribution, flow, and fitness in agriculturally important crop plants.Given the fundamental role that plasmodesmata play in the biology of plants as intercellular communication channels, we know so little about the molecular architecture and mechanisms underlying the plasmodesmal association and regulation. Numerous plant viral proteins, both soluble and membrane-attached, have been studied for a few decades in search for some clues about their plasmodesmal targeting signals and mechanisms. However, no universal signal or mechanism was identified. To address this gap in the current knowledge, the research team aims to unveil molecular mechanisms underlying plasmodesmal-targeting/retention using innate plasmodesmal regulators called the Plasmodesmata-located Proteins (PDLPs). These protein families are found to share an evolutionarily conserved feature which is required for their plasmodesmal localization and function; this novel domain is here named the Plasmodesmata-association & activation Cassette (PaaC). The outcomes of in-depth investigations of the PaaC domain, will provide unprecedented mechanistic insights into how plasmodesmata-associated integral membrane proteins are targeted and anchored at plasmodesmata, and how they may self-assemble to form functional protein complexes. To achieve these goals, the research team will take an integrative computational approach utilizing newly developed machine learning tools and techniques in combination with the state-of-the-art bioimaging techniques. It is anticipated that computational extraction and identification of complex features underlying the PaaC and PaaC-like signals will also serve as a valuable means to identify previously unrecognized plasmodesmal proteins that are encoded by various plant genomes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

许多人类疾病和发育缺陷都与细胞间通讯功能障碍有关。同样，植物也会遭受疾病不受控制的传播，不适当的季节或环境反应，或者当细胞间通讯不受控制时器官发育不正常。这项研究建立在细胞和分子生物学以及计算建模和机器学习方面的独特专业知识基础上，旨在揭示蛋白质调节剂对连接相邻细胞的通道的重要性，并微调植物中的细胞通信。本研究所提出的新概念和新发现将作为综合的新生物信息学课程和实验室模块介绍给研究生和本科生。此外，该项目开发的软件将与源代码一起在网上免费向公众提供。此外，新产生的数据、结果和工具将被纳入现有的网络服务器，该服务器具有方便用户的界面，以便更好地为研究和教育界服务。这项研究获得的基础知识有可能被长期利用来设计基因编码的合成蛋白质，以有效地控制农业上重要的作物植物中的营养分布、流动和适合度。鉴于胞间连丝在植物生物学中作为细胞间通讯通道的基本作用，我们对胞间连丝结合和调节的分子结构和机制知之甚少。几十年来，人们对许多植物病毒蛋白（包括可溶性和膜连接蛋白）进行了研究，以寻找有关其胞间连丝靶向信号和机制的线索。然而，没有确定普遍的信号或机制。为了解决现有知识中的这一差距，研究小组的目标是利用称为胞间连丝定位蛋白（PDLPs）的先天胞间连丝调节因子来揭示胞间连丝靶向/保留的分子机制。这些蛋白质家族被发现共享一个进化上保守的特征，这是它们的胞间连丝定位和功能所必需的;这个新的结构域在这里被命名为胞间连丝关联激活盒（PaaC）。PaaC结构域的深入研究的结果，将提供前所未有的机制的见解，胞间连丝相关的整合膜蛋白如何靶向和锚定在胞间连丝，以及它们如何自组装形成功能蛋白复合物。为了实现这些目标，研究团队将采用综合计算方法，利用新开发的机器学习工具和技术，结合最先进的生物成像技术。预计，计算提取和识别复杂的功能潜在的PaaC和PaaC样信号也将作为一个有价值的手段，以确定以前未被识别的胞间连丝蛋白编码的各种植物genomes.This奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。