Characterisation of Staphylococcus aureus interactions with bone cells

项目概述：这个由MRC资助的博士培训伙伴关系（DTP）将尖端的分子和分析科学与数据分析中的创新计算方法结合在一起，使学生能够解决以假设为主导的生物医学研究问题。这是一个为期4年的计划，其第一年涉及一系列教学模块和两个基于实验室的研究项目，导致跨学科生物医学研究硕士学位。前两个学期包括一系列教学模块，让学生在多学科科学中获得坚实的基础。学生还参加了一系列由学术和行业专家领导的大师班，这些专家在分子，细胞和组织动力学，微生物学和感染，应用生物医学技术以及人工智能和数据科学领域。在第三和夏季学期，学生在他们选择的实验室进行两个为期11周的研究项目。项目概述：金黄色葡萄球菌是一种细菌，可引起从轻微出血到严重心内膜炎的感染。它是医院获得性感染的主要原因。耐药菌株的增加。金黄色葡萄球菌，如耐甲氧西林的S.金黄色葡萄球菌（MRSA）的感染使得葡萄球菌感染的有效管理具有挑战性。一种主要类型的感染引起的S。金黄色葡萄球菌是骨和关节感染，特别是与假体关节相关的感染。人工关节感染（PJI）通常非常严重，慢性感染率很高，极难根除。除了治疗，由于缺乏可靠的诊断工具，慢性PJI的准确临床诊断也很困难。S.金黄色葡萄球菌能够有效地侵入骨细胞，在那里它被保护免受抗生素和我们的免疫反应。细胞内细菌在我们的细胞内生存和繁殖，并与慢性感染密切相关。在细胞内感染期间由细菌调节的细胞途径仍然不清楚，并且鉴定这些可以帮助早期诊断并提供新的药物靶点。此外，它将探索新的抗生素输送系统对细胞内的S。金黄色。在本项目中，我们将使用免疫荧光共聚焦显微镜观察S。金黄色葡萄球菌和功能基因组学方法（RNA-seq），以确定在感染过程中受到调控的基因。我们还将合成新的抗生素输送系统，针对细胞内的S。使用抗微生物聚合物的金黄色葡萄球菌。在这个项目中，学生将接受高分子化学方法和定量技能的培训，如活显微镜和生物信息学分析。

Programme overview:This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice. Project overview: Staphylococcus aureus is a bacterium responsible for infections ranging from minor abscesses to severe endocarditis. It is a leading cause of hospital-acquired infections. The rise in drug resistant strains of S. aureus, such as methicillin resistant S. aureus (MRSA), has made effective management of staphylococcal infections challenging. A major type of infection caused by S. aureus is the bone and joint infections, particularly those associated with prosthetic joints. Prosthetic joint infections (PJI) are often very serious, with high rates of chronic infections, which are extremely hard to eradicate. In addition to treatment, accurate clinical diagnosis of chronic PJI is also hard, due to a lack of reliable diagnostic tools. S. aureus is able to effectively invade bone cells, where it is protected from antibiotics and our immune responses. Intracellular bacteria survive and multiply within our cells and have been strongly linked to chronic infections. The cell pathways that are modulated by the bacterium during intracellular infection remain unclear, and identification of these could aid early diagnosis and provide new drug targets.The aim of this project is to identify bacterial and host proteins that are key to bone cell infection. Additionally, it will explore novel antibiotic delivery systems against intracellular S. aureus. During this project, we will use immunofluorescence confocal microscopy to characterise the intracellular bone cell infection profiles of S. aureus and functional genomics methods (RNA-seq) to identify genes that are regulated during infection. We will also synthesise novel antibiotic delivery systems against intracellular S. aureus using antimicrobial polymers. During this project the student will receive training in polymer chemistry methods and in quantitative skills such as live microscopy and bioinformatic analysis.