System for the Large-scale Production of Membrane Proteins

Membrane proteins play a fundamental and critical role in cellular processes. Their direct link to human disease as well as their key role in signal transduction, has made many membrane proteins the foremost targets for chemotherapeutic intervention with more than 50% of all drugs designed to modulate the activity of this class of proteins. Despite this central role in human health, the biochemical, functional and structural properties of membrane proteins remain poorly understood. This is partially due to the inherent challenges of isolating membrane proteins in sufficient quantities and levels of purity needed for biochemical characterization. The traditional approach of using heterologous protein expression systems to synthesize recombinant membrane proteins has been marginally successful. No one system has emerged as universally applicable and the process of producing recombinant membrane proteins remains one of trial and error. To address this bottleneck in the study of membrane proteins and in the development of new treatment options, we have proposed the use of the thylakoid membrane system of the unicellular green algae Chlamydomonas as a more suitable platform for the production of recombinant membrane proteins. The proposed research aims to demonstrate the feasibility of using such a system by building a set of specialized vectors that direct the expression of membrane proteins to the thylakoid membrane and to test the utility of the system using two medically relevant membrane proteins.