Project Background

Background

Type one diabetes is characterized by the body’s inability to produce insulin and is caused by the death or malfunction of the ß-cells in the pancreas. Insulin is the hormone that decreases the blood glucose concentration by inducing the cellular intake of glucose.

Insulin is produced in the Islets of Langerhans (a section of the pancreas) where glucose in the blood is detected. ß-cells in this region produce insulin by monitoring the ratio of ATP (adenosine triphosphate) versus ADP (adenosine diphosphate). When the ATP level is increased, the K+ channels close, creating an increase of Ca+ ions in the cell. The unbalance of ions signals the golgi complex to secrete insulin. If the ß-cells die or malfunction, insulin cannot be produced. (http://www.abcam.com/index.html?pageconfig=resource&rid=10602&pid=7)

Project Justification

In the United States alone, it is estimated that 3 million people are affected by type one diabetes. Complications that arise due to this disease include heart disease, stroke, high blood pressure, blindness, kidney disease, and neuropathy. The American Diabetes Association has estimated that diabetes costs America over $200 billion per year in diagnosis and treatment (http://www.diabetes.org ).

Many of the complications that arise from diabetes can be prevented by being able to test blood glucose levels and take insulin shots at appropriate times. Future applications of this project have the potential to make more affordable blood glucose test strips for people without access to good health care all over the world.

Project Inspiration

When our group was brainstorming project ideas, a team member spoke up and announced that he has been afflicted with type one diabetes since he was a child. He asked the group if synthetic biology could be used to help people like him with this disease. Research into the topic soon revealed that, in 2007, the Taipei iGEM team had already come up with an answer (http://parts.mit.edu/igem07/index.php/Taipei). They had designed a system with a glucose sensitive promoter and an eYFP reporter gene. This gene could be substituted for an insulin production gene, so that when glucose is present in the environment, insulin is produced. This system has applications in insulin pump technologies.

Unfortunately, biobricks for this complete system were not entered into the registry. Our team decided to continue their work so these biobricks could be available on the registry. In addition to submitting this part to the registry our team wanted to modify the part so that it could be sensitive to glucose at multiple concentrations. By doing this, we could use the biobrick to develop an economical glucose sensor.

Project Goal

Our goal is to model a system that can measure glucose levels at different concentrations. In the future, this system could lead to cheaper blood glucose testing devices or an economic and efficient insulin pump. To achieve this goal we are utilizing the EnvZ-OmpR two-component regulatory system. If the OmpR binding region were to be mutated, theoretically, the system would be sensitive to glucose at different glucose concentrations. Each of these mutations could then be isolated and characterized. Once an adequate number of mutants is identified, the fluorescence reporter gene could be substituted with other reporter genes (e.g. a spectrum of color genes) to make an inexpensive glucose sensor. eYFP could also be replaced with an insulin gene so the system produces insulin at specific concentrations of glucose. In the future, this system could possibly be used as an insulin pump to replace insulin in the body when needed.