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Team:Lethbridge Canada
From 2012hs.igem.org
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Project Description
==Diabetes== The purpose of our project is to create bacteria that will detect blood sugar levels and respond accordingly by producing insulin. Type one diabetes is caused by the degeneration of islet cells in the pancreas. Conventional methods of treatment for type one diabetes include direct injection of insulin intravenously, the transplantation of islet cells or even the introduction of an entirely new pancreas. Our engineered bacteria would provide a long-term solution compared to the standard injections, which need to be administered at least twice per day. In essence, our project has the potential to change the way that diabetes is treated.
Glucose Detection
For our project, a method of detecting glucose is necessary for our E. coli to initiate insulin transcription. If a change in blood sugar cannot be detected by the cell, then either insulin will not be produced or it would be overproduced. To engineer this, we plan to incorporate glucose transporter-2 (GLUT-2), already found in islet cells. GLUT2, also known as solute carrier family 2 (facilitated glucose transporter) or member 2 (SLC2A2), is a transmembrane carrier protein that allows passive glucose movement across cell membranes, which enables the rapid equilibrium of glucose concentrations on either side of the cell membrane. We will couple this with the use of a promoter that is sensitive to glucose (and possibly other sugars) and only active at a certain concentrations so the cells do not overproduce insulin at what would be considered a normal blood sugar level.
Insulin Production and Secretion
This glucose sensitive promoter will be coupled to the DNA for the production of the 51 amino acid polypeptide insulin (human insulin). Insulin needs to be produced and then exported out of the cell in order for the insulin to decrease the blood glucose levels. For export of insulin, we plan to use a signal sequence that directs the cell to transport the insulin protein outside of the cell. This can be fused to the DNA that is in charge of the insulin production.
Delivery System
The delivery system of our organism to detect glucose and produce insulin can be through direct delivery in the bloodstream or through the NASA Bio capsule. It is feasible to use a system that enters the blood stream because there are already millions of E. coli cells in our body, and we can use a strain that does not cause an immune response. Alternatively, the NASA Bio capsule, which is a tangle of carbon nanotubes that will be used to contain particular cells and eventually medicinal substances inside it, could also be used. The capsule could contain our cells, and, should the body need insulin, automatically start secretion. The Bio capsule is tiny, inserted into the skin, non-reactive and fast acting.
