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.

开发生物系统基因基因的精确控制的系统仍然至关重要，这是针对生物技术和医学领域的当前挑战。了解细胞如何控制和重新排列遗传操作，尤其是在压力条件下，可能会导致生存生物的有效工程，以适应对不同环境的适应性。最终，合成基因网络领域的进步将使新方案的开发产生感兴趣的化合物。在分子水平上，控制基因行为的一些最复杂的天然网络涉及蛋白质和核酸。然而，将相关蛋白质和核酸共同调节其基因靶标的多种方式解密，在很大程度上未知。在这个项目中，一组研究人员使用实验和建模工具来探索与保守的细菌基因调节网络有关的机制，该基因调节网络控制营养应激下的代谢。该项目为来自低收入人数不足社区的学生提供了研究机会，并为跨学科课程工程进行了贡献，以进行变革以支持STEM学生。开发用于精确控制生物系统基因的系统，对于推进合成生物学领域的发展仍然至关重要。转录后调节网络涉及调节mRNA和SRNA的RNA结合蛋白，尽管期望它们说明了对基因表达的强大和及时控制的精致天然方案，但仍在很大程度上被研究了。在这个项目中，包括研究生和本科生在内的一个跨学科研究人员探索了RNA结合蛋白在保存良好的细菌中心全球全球全球碳代谢网络中使用的新的可疑调节机制。具体而言，团队将下一代测序，显微镜，生物分子表征技术，传统的遗传学方法和计算工具结合在一起：（i）研究细菌冷凝物的形成作为转录后基因调节活性的机制，以及（ii）阐明动态调节性调节性的偶然性均可互动的情况。预计这项工作的结果将有助于开发细菌系统的新型控制机制，这些机制与天然细胞代谢更为自然。该奖项反映了NSF的法定任务，并被认为是通过基金会的智力优点和更广泛的影响来通过评估来支持的。