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

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，当细胞间的通讯不受控制时，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，或不适当的器官发育。这项研究基于细胞和分子生物学、计算建模和机器学习方面的独特专业知识，旨在揭示蛋白质调节剂对植物中连接邻近细胞和微调细胞通信的通道的重要性。本研究的新概念和新发现将作为整合的新生物信息学课程和实验模块介绍给研究生和本科生。此外，从这个项目开发的软件将与源代码一起在网上免费提供给公众。此外，新产生的数据、结果和工具将被整合到一个现有的网页服务器上，以方便用户使用，以便更好地为研究和教育界服务。从长远来看，本研究获得的基础知识有可能用于设计基因编码合成蛋白，以有效控制农业重要作物植物的营养分配、流动和适应性。虽然胞间连丝在植物生物学中作为细胞间通讯通道发挥着重要作用，但我们对胞间连丝的分子结构和调控机制知之甚少。许多植物病毒蛋白，包括可溶性的和膜附着的，已经被研究了几十年，以寻找关于它们的胞原粒靶向信号和机制的一些线索。然而，没有普遍的信号或机制被确定。为了解决当前知识中的这一空白，研究小组旨在利用称为Plasmodesmata-located Proteins （ppdlp）的先天plasmodesmal调节剂揭示plasmodesmata -targeting/retention的分子机制。这些蛋白家族被发现共享一个进化上保守的特征，这是它们的浆粒定位和功能所必需的；这个新结构域在这里被命名为胞间连丝关联激活盒（PaaC）。深入研究PaaC结构域的结果，将提供前所未有的机制见解，了解胞间连丝相关的整体膜蛋白如何靶向并锚定在胞间连丝上，以及它们如何自组装形成功能性蛋白复合物。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PaaC和PaaC样信号背后的复杂特征也将作为鉴定以前未被识别的各种植物基因组编码的胞浆连丝蛋白的有价值的手段。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.