Characterisation of Staphylococcus aureus interactions with bone cells

课程概述：这个由MRC资助的博士培训伙伴关系(DTP)将尖端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，使学生能够解决假设引导的生物医学研究问题。这是一个为期4年的课程，第一年包括一系列的教学模块和两个基于实验室的研究项目，这些项目导致了跨学科生物医学研究的硕士学位。前两个学期包括精选的教学模块，使学生能够在多学科的科学中获得坚实的基础。学生们还参加了由学术和行业专家主持的一系列大师课程，这些专家涉及分子、细胞和组织动力学、微生物学和传染病、应用生物医学技术以及人工智能和数据科学等领域。在第三学期和暑期，学生们在他们选择的实验室里进行两个为期十一周的研究项目。项目概述：金黄色葡萄球菌是一种细菌，可引起从轻微脓肿到严重心内膜炎的各种感染。它是医院获得性感染的主要原因。耐甲氧西林金黄色葡萄球菌(MRSA)等耐药菌株的增加，使有效控制葡萄球菌感染具有挑战性。金黄色葡萄球菌引起的一种主要感染类型是骨骼和关节感染，特别是与假肢关节相关的感染。假体关节感染(PJI)通常非常严重，慢性感染率很高，极难根除。除了治疗外，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。金黄色葡萄球菌能够有效地入侵骨骼细胞，在那里它受到抗生素和我们的免疫反应的保护。细胞内细菌在我们的细胞内存活和繁殖，并与慢性感染密切相关。细菌在细胞内感染过程中调节的细胞通路尚不清楚，识别这些通路有助于早期诊断并提供新的药物靶点。该项目的目的是鉴定对骨细胞感染至关重要的细菌和宿主蛋白。此外，它还将探索针对细胞内金黄色葡萄球菌的新型抗生素输送系统。在这个项目中，我们将使用免疫荧光共聚焦显微镜来表征金黄色葡萄球菌细胞内的骨细胞感染情况，并使用功能基因组学方法(RNA-seq)来识别在感染过程中受到调控的基因。我们还将使用抗菌聚合物合成针对细胞内金黄色葡萄球菌的新型抗生素递送系统。在这个项目中，学生将接受聚合物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.