Using Cholera toxin B-chain as a system for the targeted delivery of proteins to motor neurons (360G-Wellcome-102576_Z_13_Z)

The aims of the project are to design a method for the reversible binding of antibody-like proteins to Cholera Toxin B subunit (CTB) to facilitate their trafficking into cells. Initially, a screen against CTB will be carried out toidentify suitable Adhirons. These will be conjugated to a range of different proteins, before being combined with CTB, and administered to assess its ability to deliver the complex into motor neurons in vivo. There is currently no method to deliver antibody-like molecules into motor neurons selectively. Sublingual injection of CTB allows this group of neurons to be targeted specifically. This project therefore focuses on the design of an enabling technology to permit delivery of proteins into specific cell typesto address questions in neurobiology. By combining techniques from molecular biology and chemistry to generate the binding complex, and assessing the effect of these complexes on the nervous system in vivo, this project will provide an interdisciplinary approach to understanding neuronal function at the molecular level. Therefore, this project addresses one of the Wellcome Trusts five major research challenges, i.e., understanding the brain.