Understanding the molecular mechanism of bacterial sphingolipid synthesis

了解细菌鞘脂合成的分子机制

• 批准号: 2884596
• 金额: --
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2884596
• 关键词: Understanding; molecular; mechanism; bacterial; sphingolipid

Bacteria produce a wide range of membrane lipids and our understanding of these is growing, with recent work showing that they produce lipids that were previously thought to only be produced by eukaryotes, including an array of different sphingolipids. Sphingolipids are key structural components of eukaryotic membranes, and they also play key roles in intra- and inter-cellular signalling. Recently they have been discovered in key human microbiome species, including Bacteroides thetaiotaomicron and Escherichia coli.The project aims are to determine the structure and function of the key enzymes involved in the early stages of sphingolipid biosynthesis in E. coli and understand how the expression of these enzymes is regulated in response to environmental and host factors. In this project the student will use molecular cloning to produce protein expression constructs; they will produce recombinant protein in an Escherichia coli expression host; and use chromatography methods to purify the recombinant proteins. The student will develop skills in structural biology and biochemistry methods to characterise the structure and function of these proteins. This multidisciplinary project combines expertise in structural biology and biochemistry with expertise in the study of gene regulatory networks in key host/microbe interactions additional expertise in structural biology will come from Durham partner. The student will also have extensive opportunities to work with our collaborators at Edinburgh University and Rutgers University. Ultimately this project will help us develop our understanding of the biosynthetic pathways used by bacteria to produce these important membrane lipids and how their expression is controlled in a host context. The project outcomes will have impact in understanding host microbe interactions and may provide new targets for the development of antimicrobial molecules.

细菌产生多种膜脂，我们对这些膜脂的了解正在不断加深，最近的研究表明，细菌产生的脂质以前被认为只能由真核生物产生，包括一系列不同的鞘脂。鞘脂是真核细胞膜的关键结构成分，在细胞内和细胞间信号传导中也发挥着关键作用。最近在关键的人类微生物组物种中发现了它们，包括多形拟杆菌和大肠杆菌。该项目的目的是确定大肠杆菌中鞘脂生物合成早期阶段涉及的关键酶的结构和功能，并了解这些酶的表达如何这些酶根据环境和宿主因素进行调节。在这个项目中，学生将使用分子克隆来产生蛋白质表达结构；他们将在大肠杆菌表达宿主中生产重组蛋白；并利用层析方法纯化重组蛋白。学生将培养结构生物学和生物化学方法的技能，以表征这些蛋白质的结构和功能。这个多学科项目结合了结构生物学和生物化学的专业知识以及关键宿主/微生物相互作用中基因调控网络研究的专业知识，结构生物学的其他专业知识将来自达勒姆合作伙伴。学生还将有广泛的机会与我们在爱丁堡大学和罗格斯大学的合作者一起工作。最终，该项目将帮助我们加深对细菌用于产生这些重要膜脂的生物合成途径的理解，以及它们的表达如何在宿主环境中受到控制。该项目的成果将对理解宿主微生物的相互作用产生影响，并可能为抗菌分子的开发提供新的目标。