Single molecule techniques for antibody adsorption and manipulation

抗体现在在疾病诊断和治疗中起着核心作用，例如在癌症治疗的免疫疗法中。将抗体输送给患者涉及一系列生物物理学方面的挑战。高浓度的抗体导致高粘弹性，导致胶体系统因运输受限而堵塞。此外，抗体可与制剂生产工艺相互作用。例如，加工设备或最终药物容器的表面可能导致它们吸附和变性。这对药物疗效和患者安全构成风险。相稳定性也是一个大问题，因为蛋白质的聚集会破坏它们的功能。学生将接受培训，使用一系列单分子技术来实验性地探测抗体的行为，然后开发一些简单的软物质模型来描述所涉及的物理现象。我们将使用磁镊，荧光显微镜（TIRF和STORM）和微观流变学来探索单分子水平的现象。统计模型将被开发来描述的干扰现象，表面吸附，蛋白质构象，粘弹性和介观相互作用潜力。学生将在曼彻斯特进行研究，但将在Medimmune（剑桥）进行一些研究和培训。因此，该项目为学生提供了一个独特的培训机会，学习如何将领先的生物物理研究与先进的制药应用联系起来。

Antibodies now play a central role in disease diagnosis and treatment e.g. in immunotherapies for cancer treatment. The delivery of the antibodies to patients involves a series of challenges in terms of their biological physics. High concentrations of the antibodies lead to high viscoelasticities causing the colloidal systems to become jammed with limited transport. Furthermore, the antibodies can interact with the drug product manufacturing process. For example, the surfaces of processing equipment or final drug containers can cause them to adsorb and denature. This poses risks to drug efficacy and patient safety. Phase stability is also a big issue, since aggregation of the proteins can disrupt their functioning. The student will be trained to use a series of single molecule techniques to experimentally probe the behavior of antibodies and then develop some simple soft matter models to describe the physical phenomena involved. We will use magnetic tweezers, fluorescence microscopy (TIRF and STORM) and microrheology to explore the phenomena at the level of single molecules. Statistical models will be developed to describe the jamming phenomena, surface adsorption, protein conformations, viscoelasticity and mesoscopic interaction potentials. The student will base his research at Manchester, but will undertake some research and training at Medimmune (Cambridge). The project thus provides a unique training opportunity for the student to learn how to link leading biophysical research to advanced pharmaceutical applications.