Team:Imperial College London/M1

Overview

 Module 1 in our design defines the application of our E.ncpsulator vector. In fact, module 1 determines the protein that is produced by the bacterium and that is aimed for delivery to the gut. It is essential to note that the E.ncapsulator project is versatile with regard to the protein being produced and thus to diseases it targets or the functions it adds.
To make proof of principle for the iGEM competition, we have decided to produce two different enzymes: cellulase and PhenylAlanine Hydroxylase (PAH).

Cellulase is an enzyme able to catalyse (degrade) cellulose, a material widely available in our diet. However, the human body is unable to degrade cellulose into glucose naturally. By producing a special cellulase (able to degrade cellulose to glucose on its own) in our E.ncapsulator system, we would perform the delivery of cellulase enzyme to the digestive region of the gut, thus enabling the degradation of cellulose into glucose. In other words, people ingesting E.ncapsulated pills of cellulase would be able to derive energy from eating grass, wood or other cellulose-containing materials.

PenylAlanine Hydroxylase is a liver enzyme that degrades essential amino acid Phenylalanine into Tyrosine. PhenylKetonUria (PKU) is a condition associated to the creation by the body of a defective version of the PAH enzyme. As a consequence, individuals with this disease are unable to breakdown phenylalanine which causes its accumulation in the blood and brain ultimately causing severe damages to the brain resulting in mental retardation. Current treatment of this disease is limited severe diet restriction and one drug (Kuvan). The problem is that Kuvan is in fact a drug that delivers BH4 (tetrahydropbiopterin), a cofactor to PAH, and therefore only treats roughly half of Phenylketonuriacs (Matalon et al., 2004). By using the E.ncapsulator system to deliver PAH to the gut, we are enabling a better control of the disease and providing a complementary solution to it.

 This module is the key customisable component of our system, allowing the scientist to develop E.ncapsulator delivery systems bearing the enzyme of choice. This customisation is achievable by replacing only one gene in the genetic circuit.