Characterizing the role of YjiS in Salmonella virulence

表征 YjiS 在沙门氏菌毒力中的作用

• 批准号: 379643359
• 负责人: Professor Dr. Jörg Vogel
• 金额: --
• 依托单位: Institut für Molekulare Infektionsbiologie (IMIB)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/379643359?language=en
• 关键词: Characterizing; role; YjiS; Salmonella; virulence

The first funding period was used to develop an integrative workflow combining new and existing datasets with the aim to compile a global overview of sORFs in the model human pathogen Salmonella enterica serovar Typhimurium, with special emphasis on sORFs with putative roles in bacterial virulence. The pipeline was designed to be universal applicable to other organisms and research question underlining its usefulness for a broader research community. The applicability of the proposed approach was demonstrated by novel insights into MgrB activity as well as the prioritization of the small DUF1127 domain protein YjiS as candidate for in-depth analysis in the second funding period. We now plan to use advanced techniques such as Dual RNA-seq and ribosome profiling, together with classical molecular biology approaches, to identify the regulon and interactome of YjiS and the impact of this small protein on Salmonella virulence. At the end of the project we will have performed an in-depth analysis of the role of YjiS in regulating virulence during macrophages infection. We will investigate this from different points of view, such as the pathways YjiS might be involved in, and the changes it induces in the host response to infection. We will describe the molecular mechanism of action that YjiS employs, and draw a comprehensive picture of how it affects different aspects of virulence. In parallel, we will initiate validation of our newly predicted STsORFs and perform a preliminary analysis to identify the ones with an infection phenotype. With this, we will have obtained a better picture of how small proteins are used by Salmonella to adapt to and manipulate the host environment.

第一个资助期用于开发一个综合工作流程，结合新的和现有的数据集，目的是编制模型人类病原体肠沙门氏菌血清型鼠伤寒沙门氏菌中sorf的全球概况，特别强调在细菌毒力中可能起作用的sorf。该管道被设计为普遍适用于其他生物体和研究问题，强调其对更广泛的研究社区的有用性。通过对MgrB活性的新见解以及DUF1127结构域小蛋白YjiS作为第二个资助期深入分析的候选蛋白的优先级，证明了所提出方法的适用性。我们现在计划使用先进的技术，如双RNA-seq和核糖体分析，结合经典的分子生物学方法，确定YjiS的调控和相互作用，以及这种小蛋白对沙门氏菌毒力的影响。在项目结束时，我们将对巨噬细胞感染期间YjiS在调节毒力中的作用进行深入分析。我们将从不同的角度来研究这一点，比如YjiS可能参与的途径，以及它在宿主对感染的反应中引起的变化。我们将描述YjiS使用的分子作用机制，并绘制它如何影响毒力不同方面的综合图片。同时，我们将开始验证我们新预测的stsorf，并进行初步分析以识别具有感染表型的stsorf。有了这个，我们将更好地了解沙门氏菌是如何利用小蛋白质来适应和操纵宿主环境的。