Single molecule techniques for antibody adsorption and manipulation

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.