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

在生物系统中开发精确控制基因的系统对于推进当前生物技术和医学的挑战仍然是至关重要的。了解细胞如何控制和重新安排基因操作，特别是在压力条件下，可以有效地改造生物体，用于需要对不同环境进行强大适应的应用。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例如感兴趣的化合物。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，破译相关蛋白和核酸共同调节其基因目标的许多方式在很大程度上仍然未知。在这个项目中，一组研究人员使用实验和建模工具来探索在营养压力下控制代谢的保守细菌基因调控网络所涉及的机制。该项目为来自低收入群体的学生提供了研究机会，并为试点一门跨学科课程“工程变革”做出了贡献，以支持STEM学生。在生物系统中开发精确控制基因的系统对于推进合成生物学领域至关重要。转录后调控网络，包括调控mrna和sRNAs的rna结合蛋白，在很大程度上仍未得到充分研究，尽管人们期望它们阐明了强大而及时的基因表达控制的复杂天然方案。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可疑调节机制。具体来说，该团队将下一代测序，显微镜，生物分子表征技术，传统的体内遗传方法和计算工具结合起来：(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）阐明作为调节结合位点替代使用的动态调节结果。这项工作的结果有望帮助开发与天然细胞代谢更自然地一致的细菌系统的新控制机制。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。

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.