NSF-sponsored workshop: The cross-disciplinary study of post-transcriptional and post-translational modifications: Finding the commonalities of interests, approaches, and future di

地球上的每一个有机体都依赖其DNA含量(即基因组)来指导其生命、生长和发育。然而，基因组并不是生物体的命运。例如，毛虫和蝴蝶的基因组完全相同，但形式不同。这种差异在很大程度上可以归因于基因组编码的其他重要生物分子。这些生物分子是RNA和蛋白质，它们在合成后可以通过数百种不同的方式进行修饰。对RNA和蛋白质修饰的多样性和复杂性的认识已经从根本上改变了我们对这些分子在从微生物到植物和人类的大小生物体中不同功能的看法。了解RNA和蛋白质是如何被修饰的，以及它们的生物学含义，在许多基础和应用生物学和医学研究领域非常重要。提高我们的理解将需要建立社区资源、技术突破和跨学科研究努力，以实现RNA和蛋白质生物学的交叉进展。该项目将支持一个虚拟的国家讲习班，使100-150名积极参加会议和讨论的不同参与者汇聚一堂。此外，所有研究讲座和讨论环节都将开放给任何有兴趣的人通过Zoom观看。参与者来自许多不同的学科和领域，包括植物、动物和人类生物学，涵盖化学、工程、计算机科学、人工智能、系统和合成生物学等研究领域。领导、小组和互动会议的主旨演讲将促进和激励研究人员讨论以下关键主题：1)各种研究生物体中RNA和蛋白质修饰研究的成功和失败；2)利用所有与RNA和蛋白质相关的科学学科的实验系统和研究方法；3)可能的“生命规则”，以指导不同生物体领域的基线和比较问题；4)现有工具、联盟和数据库的优缺点；5)对能够促进RNA和蛋白质生物学未来进步的研究人员的培训需求；6)中短期研究和知识目标，指出实现这些目标的潜在策略。在我们目前对遗传信息流的理解框架内，RNA分子的转录后修饰(PRM)和蛋白质的翻译后修饰(PTM)是极其重要的细胞调节部分。然而，在对这两个调控部分及其对不同生物有机体整体细胞新陈代谢的影响的综合理解方面，仍然存在显著的差距。不同系统(如微生物、植物、动物和人类)的零散研究工作，以及使用不同的方法和标准，阻碍了对不同数据集的综合分析和对可再生能源和可再生能源的共同原则的确定。这次研讨会旨在填补这些空白，并推动研究从描述性和具体的机制重点转向综合、一般理论、建模和预测以及全球理解。此外，这次研讨会将促进研究关键调节修饰的功能和机制，研究它们在细胞信号和新陈代谢中的作用，以及它们对生物体的影响。研讨会将通过确定：1)驱动/激励PRM和PTM研究的核心问题；2)为假设检验提供有用的镜头的概念和理论基础；3)推动这些领域的进步和对生命规则的更多了解的大想法；以及4)合作研究和综合分析的前进道路，以推动这些领域的进步和对生命规则的理解；以及4)通过多学科方法进一步整合这两个密切相关的研究领域的合作研究和综合分析的前进道路。职业生涯初期的博士后科学家和研究生将参加研讨会组织并担任虚拟讨论领袖，为他们提供与这些前沿领域的许多领袖建立网络的机会。讲习班旨在增加未被充分代表的群体对RNA和蛋白质修饰研究的广泛参与，并作为整合包容性和互动性在线会议机会的典范，使更广泛的受众能够参与。总的来说，这次研讨会将确定在资源和对跨学科的PRM和PTM的理解方面的关键差距，并重要的是为社区范围内的协作研究起草一条前进道路，以促进这些影响我们对人类、植物、动物和生态系统生物学的理解的重要研究领域。本次研讨会的资金由生物理事会的生理和结构系统群、植物基因组研究计划和遗传机制群以及ENG理事会的细胞和生化工程计划提供。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Every organism on earth relies on its DNA content (i.e., genome) to direct its life, growth, and development. However, the genome is not the destiny of the organism. For example, caterpillars and butterflies have exactly the same genome, but distinct forms. The difference can be largely attributed to the other important biomolecules that are encoded by the genome. These biomolecules are RNA and proteins, which can be modified in hundreds of different ways after their synthesis. Recognition of the diversity and complexity of modifications of RNA and proteins has changed how we think about their different functions of these molecules in fundamental ways in both large and small organisms, ranging from microbes to plants and humans. Understanding how RNA and proteins are modified, and their biological implications is very important in many areas of basic and applied biological and medical research. Improving our understanding will require building community resources, technical breakthroughs, and cross-disciplinary research efforts to achieve cross-cutting advances in RNA and protein biology. This project will support a virtual national workshop that will bring together 100-150 diverse participants that are actively involved in both the meeting and discussion sessions. In addition, all research talks, and discussion sessions will be open for anyone interested to watch through Zoom. The participants are from many different disciplines and areas, including plant, animal, and human biology, and cover research areas such as chemistry, engineering, computer science, artificial intelligence, and systems and synthetic biology. Keynote talks from leaders, small-group and interactive sessions will facilitate and stimulate researchers to address the following key topics: 1) Successes and failures in RNA and protein modification research in a variety of research organisms; 2) Experimental systems as well as research approaches that leverage all RNA and protein–related scientific disciplines; 3) Possible “rules of life” to guide baseline and comparative questions across the different realms of organisms; 4) Advantages and disadvantages of currently available tools, consortia, and databases; 5) Training needs for researchers capable of contributing to future advancement in RNA and protein biology; and 6) Short- and medium-term research and knowledge goals, noting potential strategies to reach these goals.In the framework of our current understanding of genetic information flow, post-transcriptional modifications (PRMs) of RNA molecules and post-translational modifications (PTMs) of proteins are extremely important cellular regulatory moieties. Yet significant gaps remain in the integrated understanding of these two regulatory moieties and their effects on overall cellular metabolism in different biological organisms. Fragmentated research efforts in different systems (e.g., microbe, plant, animal, and human) and using different approaches and standards, has prevented integrative analyses of different datasets and identification of common principles of PRMs and PTMs. This workshop aims to fill these gaps and advance research from descriptive and specific mechanistic focus towards integration, general theory, modeling and prediction, and global understanding. Moreover, this workshop will promote studying the functions and mechanisms of the key regulatory modifications, of their roles in cellular signaling and metabolism, as well as their impact on organisms. The workshop will provide significant opportunities for cross-disciplinary interactions to advance the field of RNA and protein biology by identifying: 1) core questions driving/motivating PRM and PTM studies; 2) conceptual and theoretical foundations that provide a useful lens for hypothesis testing; 3) big ideas to drive advances in these areas and increased understanding of the rules of life; and 4) a path forward for collaborative research and synthetic analyses that will further integrate the two closely-related areas of research through multidisciplinary approaches. Early-career post-doctoral scientists and graduate students will participate in the workshop organization and serve as virtual discussion leaders, providing them the opportunity to network with many of the leaders in these cutting-edge fields. The workshop aims to increase broad participation of underrepresented groups in RNA and protein modification research, and serves as a model for integration of inclusive and interactive online conference opportunities allowing participation from broader audiences. Collectively, this workshop will identify critical gaps in resources and understanding of PRMs and PTMs across disciplines, and importantly draft a path forward for community-wide collaborative research to advance these important areas of research that affect our understanding of human, plant, animal, and ecosystem biology. Funding for this workshop was provided by the Physiological and Structural Systems Cluster, Plant Genome Research Program, and Genetic Mechanisms Cluster in the BIO Directorate and the Cellular and Biochemical Engineering Program in the ENG Directorate.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.