PhD ceremony Ms. N. Mukherjee: Control over translocation across the lipid bilayer via an engineered channel protein

PhD ceremony: Ms. N. Mukherjee

Dissertation: Control over translocation across the lipid bilayer via an engineered channel protein

Promotor(s): prof. B. Poolman

Faculty: Mathematics and Natural Sciences

Nature has provided a repertoire of solutions to address some of the scientific problems that we face. A cell uses channel proteins to establish communication across the lipid bilayer. There is a need for translocation of solutes and cargo in many biological systems, like drug delivery device. Taking a cue from the cell, we made an effort to use bacterial channel protein, MscL as a nanovalve in drug delivery system and as sensing module in a nanochip. With this as the goal, the thesis answers: “how can MscL be activated by non-natural triggers?” and “how can we use this externally-controlled nanovalve for different applications?”

In bacteria, MscL senses the mechanical disturbances in the membrane due to environmental stress and helps the bacteria to survive. We have engineered MscL such that it can sense the pH or can be activated by chemical molecules. In one of the applications, pH sensitive MscL is used for controlled release of drug from liposomes. MscL detects the low pH of the tumor microenvironment, and releases the drug into implanted brain tumor in a mouse model. In another application as a sensory module in a nanochip, hundreds of import and export events are recorded simultaneously through MscL channels. This system can help in the characterization of new pharmaceuticals against microbial membrane proteins that serve as drug target. Thus, we have successfully utilized a nanovalve to control translocation of cargo across the lipid membrane.