Single molecule techniques for antibody adsorption and manipulation

用于抗体吸附和操作的单分子技术

• 批准号: 2288921
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2288921
• 关键词: Single; molecule; techniques; antibody; adsorption

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.

抗体现在在疾病诊断和治疗中发挥着核心作用，例如：用于癌症治疗的免疫疗法。将抗体输送给患者涉及生物物理学方面的一系列挑战。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，抗体可以与药品生产过程相互作用。例如，加工设备或最终药物容器的表面可能会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其功能。学生将接受培训，使用一系列单分子技术来实验探测抗体的行为，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。我们将使用磁力镊子、荧光显微镜（TIRF 和 STORM）和微流变学来探索单分子水平的现象。将开发统计模型来描述干扰现象、表面吸附、蛋白质构象、粘弹性和介观相互作用势。该学生的研究基地将在曼彻斯特，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，让他们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。