Borrowing an idea from bacteria, Georges Belfort and his bioseparations group are trying to engineer a novel synthetic pathway with a molecular switch. In the long term, the pathway could be used to produce complex biological molecules and make medicines targeted to act on specific cell types in the body.
Many proteins require modification to be activatedfor example, they can be cut at a defined point by other proteins. An alternative mechanism was recently discovered in bacteria by which certain proteins dissect themselves. While the chemical reactions involved in this self-splicing action are known, the mechanisms both in terms of structural positioning and necessary conditions are not. “Once you understand the mechanism, you can control it,” says Belfort, the Russell Sage Professor of Chemical and Biological Engineering.
Now researchers are closer to understanding how self-splicing proteins work. Belfort and his team, which includes molecular and structural biologists (Marlene Belfort and Patrick Van Roey at the Wadsworth Center, Albany), molecular modelers (Shekhar Garde’s group in chemical and biological engineering), nuclear magnetic resonance spectroscopists (Chunyu Wang in biology), and quantum mechanicists (Saroj Nayak’s group in physics), are trying to put analogous molecular switches onto a variety of proteins and to scale the process down and onto a chip.
In trying to manipulate the reaction, they have learned plenty about the mechanism, which was reported this year in Biophysical Journal. If the reaction can be harnessed, it may have application as biological sensors, for targeted drug delivery, and for synthesis of new therapeutic drugs.