Single molecule techniques for antibody adsorption and manipulation

抗体现在在疾病诊断和治疗中发挥着中心作用，例如在癌症治疗的免疫疗法中。将抗体传递给患者涉及到他们的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，导致胶体系统被有限的运输堵塞。此外，抗体可以与药物产品的制造过程相互作用。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了风险。相态稳定性也是一个大问题，因为蛋白质的聚集可能会扰乱它们的功能。学生将接受培训，使用一系列单分子技术对抗体的行为进行实验探测，然后开发一些简单的软物质模型来描述相关的物理现象。我们将使用磁镊子、荧光显微镜(TIRF和STORM)和微观流变学在单分子水平上探索这一现象。将建立统计模型来描述堵塞现象、表面吸附、蛋白质构象、粘弹性和介观相互作用势。这名学生将把他的研究基地设在曼彻斯特，但将在剑桥的Medimmune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.