Photorhabdus Toxin Complex (PTC) as variable protein injection apparatus

• Applicant: Professorin Dr. Gudula Schmidt
• Subject Area: Pharmacology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 441232035

The project aims to further characterize and to engineer the trimeric, stand alone toxin complex (Photorhabdus luminescens toxin complex: PTC), which allows injection of cargo proteins into mammalian cells. We already showed that loading and injection of different cargo molecules, including a very small luciferase for quantification was possible. Our recently published data show that packaging and injection of proteins with a size of up to 30 kDa is possible. The project aims to study, whether injection of mammalian proteins, for example regulators of small GTPases is possible. We plan to optimize the efficiency of the injection. Therefore, we plan to analyze the requirements of a cargo molecule to be actively released into mammalian cells. Our aim is to engineer the toxin complex as universal protein injection machinery for cell biological and possibly pharmacological use. To do so, it is necessary to identify the cellular structures allowing toxin binding (receptors), to mutate the corresponding amino acids of the toxin and to attach a peptide or small protein allowing more specific cell binding.

• DFG Programme: Research Grants