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.

开发用于精确控制生物系统中基因的系统对于推进生物技术和医学中的当前挑战仍然是至关重要的。了解细胞如何控制和重新排列遗传操作，特别是在压力条件下，可能会导致有效的生物工程应用，需要强大的适应不同的环境。最终，合成基因网络领域的进展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点的许多方式仍然是未知的。在这个项目中，一组研究人员使用实验和建模工具来探索保守的细菌基因调控网络所涉及的机制，该网络控制营养压力下的代谢。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。开发用于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RNA结合蛋白，调节mRNA和sRNA，仍然在很大程度上研究不足，尽管期望他们说明了强大的和及时的控制基因表达的复杂的天然方案。在这个项目中，一个跨学科的研究团队，包括研究生和本科生，探索了RNA结合蛋白在一个保守的细菌中心全球碳代谢网络中使用的新的疑似调控机制。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，传统的遗传体内方法和计算工具：（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）阐明动态调控结果作为调控结合位点替代用途的结果。这项工作的结果预计将有助于开发新的控制机制的细菌系统，更自然地与天然细胞代谢。这个奖项反映了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。