In-situ AFM of pathogenic proteins involved in meningitis and septicaemia

许多致病细菌会分泌攻击和降解人体组织的物质(蛋白质)。我们最近发现了颠覆人类血细胞的新蛋白质，使细菌能够将其内容物用作营养物质，并在血液中生存。当一种由引起脑膜炎和败血症的细菌分泌的蛋白质进入红细胞的细胞膜时，我们应该可以跟踪它，想象由此导致的细胞形状的变化，并对这种蛋白质在细胞中所扮演的角色--S死亡--有一个新的理解。原子力显微镜(AFM)是一种成像技术，它允许我们以极高的放大倍数查看膜内的单个蛋白质。我们可以在生理条件下观察表面，并有可能实时跟踪分子尺度的过程，提供比目前传统光学或电子显微镜所能获得的更多细节。申请者最近的发展使成像速度大大加快，提供了一个实时可视化疾病建立过程中重要早期事件的机会。这项赠款旨在将专业知识从物理科学转移到医学中，提供以前没有应用于医疗问题的设备的机会和专业知识。一名物理科学家研究员将被重新安置到医学院，为她提供相当多的新培训，并为她提供将AFM技术应用于这些重要系统的独特技能。这项计划亦会让物理学家申请者有充分时间熟习与医学有关的生物学，为发展更广泛应用于医学的原子力显微镜相关新技术奠定良好基础。

Many bacteria responsible for disease secrete substances (proteins) that attack and degrade human tissue. We have recently identified new proteins that subvert human blood cells allowing bacteria to use their contents as nutrients and survive in the blood. It should be possible to follow a protein secreted by the bacteria responsible for meningitis and septicaemia as it enters the cell membrane of a red blood cell, image the resultant changes in cell shape, and gain a new understanding of role played by the protein in the cell?s demise. Atomic force microscopy (AFM) is an imaging technique that allows us to view individual proteins within membranes at extremely high magnification. We can view surfaces under physiological conditions, and potentially follow processes at a molecular scale in real-time providing much more detail than is available currently with conventional light or electron microscopy. Recent developments by the applicant allow considerably faster imaging, providing an opportunity to visualize, in real time, important early events in the establishment of disease.This grant aims to transfer expertise from physical science into medicine, providing access and expertise in equipment not previously applied to a medical problem. A physical scientist researcher will be physically re-located into the School of Medicine, providing her with considerable new training and giving her a unique skill set for applying AFM technology to these important systems. It will also give the physical scientist applicant sufficient time to become well acquainted with the medically relevant biology, providing a sound basis for the development of new AFM related technologies of wider application to medicine.