Modulating properties of antibodies using unnatural amino acids (360G-Wellcome-204593_Z_16_Z)

Recent advances in molecular biology and genetics have greatly enhanced the production of proteins with unnatural amino acids having diverse chemical properties. Proteins from several classes are now being modified using unnatural amino acids that can add to or alter the natural properties of the protein. Antibodies, with their wide range of applications through molecular biology to medicine, present an attractive class of proteins whose properties may be modulated using unnatural amino acids. In Aim 1 of this project, we propose to develop photoactive antibodies, i.e., antibodies whose binding to their corresponding antigen can be controlled using light. Such antibodies could be used as research tools to study antibody-mediated processes, and also have the potential to be developed into novel antibody-based photoactive therapeutics. In Aim 2 of this project, we propose to develop antibody-based optical switches, i.e. non-fluorescent antibodies that become fluorescent upon binding to target antigens. These switches would overcome a major limitation of current antibody-based detection methods, where immobilisation of antigen or antibody to a surface is required. Such optical switches are expected to have applications in cancer diagnosis, and in detection of viruses and bacteria.