Deciphering newly uncovered mechanisms of fluid regulation in bacterial RNA-protein networks

破译细菌 RNA-蛋白质网络中新发现的液体调节机制

• 批准号: 2349832
• 负责人: Lydia Contreras
• 金额: $ 65.02万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2349832&HistoricalAwards=false
• 关键词: Deciphering; newly; uncovered; mechanisms; fluid

Developing systems for precise control of genes in biological systems continues to be paramount for advancing current challenges in biotechnology and medicine. An understanding of how cells control and rearrange genetic operations, particularly during conditions of stress, could lead to efficient engineering of living organisms for applications that require robust adaptation to different environments. Ultimately, advances in the field of synthetic gene networks will allow development of novel schemes to produce chemical compounds of interest, for example. At the molecular level, some of the most sophisticated native networks that control gene behavior involve both proteins and nucleic acids. Yet, deciphering the many ways in which associated proteins and nucleic acids work together to regulate their gene targets remains largely unknown. In this project, a team of researchers use experimental and modeling tools to explore mechanisms involved in a conserved bacterial gene regulatory network that controls metabolism under nutritional stresses. The project provides research opportunities to students from low-income underrepresented communities and contributes to piloting a cross-discipline course Engineering for Change to support STEM students. Developing systems for precise control of genes in biological systems continues to be paramount for advancing the synthetic biology field. Post-transcriptional regulatory networks, involving RNA-binding proteins that regulate both mRNAs and sRNAs, remain largely understudied despite expectations that they illustrate sophisticated native schemes of robust and timely control of gene expression. In this project, an interdisciplinary team of researchers, including graduate and undergraduate students, explore new suspected regulatory mechanisms used by RNA-binding proteins within a well-conserved bacterial central global carbon metabolism network. Specifically, the team combines Next Generation Sequencing, microscopy, biomolecular characterization techniques, traditional genetic in vivo methods, and computational tools to: (i) Investigate the formation of bacterial condensates as a mechanism of post-transcriptional gene regulation activity, and (ii) Elucidate dynamic regulatory outcomes as a consequence of regulatory binding sites alternative usage. Results from this work are expected to aid development of novel control mechanisms of bacterial systems that are more naturally aligned with native cellular metabolism.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.

开发精确控制生物系统中基因的系统对于应对当前生物技术和医学挑战仍然至关重要。了解细胞如何控制和重新排列遗传操作，特别是在应激条件下，可以实现对生物体的有效工程改造，以满足需要对不同环境进行强有力适应的应用。最终，合成基因网络领域的进步将允许开发新的方案来生产感兴趣的化合物。在分子水平上，一些控制基因行为的最复杂的天然网络涉及蛋白质和核酸。然而，破译相关蛋白质和核酸共同调节其基因靶标的多种方式仍然很大程度上未知。在该项目中，一组研究人员使用实验和建模工具来探索保守细菌基因调控网络的机制，该网络在营养压力下控制新陈代谢。该项目为来自低收入代表性不足社区的学生提供研究机会，并有助于试点跨学科课程“变革工程”以支持 STEM 学生。开发精确控制生物系统中基因的系统对于推进合成生物学领域仍然至关重要。转录后调控网络，涉及调节 mRNA 和 sRNA 的 RNA 结合蛋白，尽管人们期望它们阐明了基因表达的强大而及时的控制的复杂的天然方案，但仍然在很大程度上未被充分研究。在这个项目中，一个由研究生和本科生组成的跨学科研究小组，探索了在保守的细菌中央全球碳代谢网络中 RNA 结合蛋白使用的新的可疑调节机制。具体来说，该团队结合了下一代测序、显微镜、生物分子表征技术、传统体内遗传方法和计算工具来：（i）研究细菌凝聚物的形成作为转录后基因调控活性的机制，以及（ii）阐明由于调控结合位点替代使用而产生的动态调控结果。这项工作的结果预计将有助于开发更自然地与天然细胞代谢相一致的细菌系统的新型控制机制。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。