Overview

An estimated one in every 133 Americans suffer from an autoimmune disorder called celiac disease (14, 11). Celiac disease is a condition in which the small intestines are unable to digest gliadin, a protein present in gluten. When gliadin is consumed by an individual with celiac disease, the immune system responds by causing a range of side-effects, which may include abdominal pain, chronic diarrhea, and/or vomiting (14). A friend of one of our teammates currently suffers from this illness, which prompted us to look into celiac disease as the focus of our project. Currently, the only accepted treatment for this disorder is adhering to a gluten-free diet (14, 12). This inspired us to design a probiotic organism that could survive and take residence in the stomach, where it would secrete an enzyme that can degrade gliadin. This would prevent gliadin from progressing through the small intestine and inducing immune system response.

This synthetically engineered organism should be able to satisfy two main criteria. First, it should be able to survive only in the stomach and secondly, it should secrete an enzyme that can degrade gliadin.

Studies have shown that the enzyme, Prolyl-endoprotease, is able to degrade gliadin at the pH level of the stomach (8). Prolyl-endoprotease is one of the most promising enzymes which are being used in recent studies regarding treatment for celiac disease.

Due to licensing restrictions, we have opted not to work with this protein.

We have decided to focus our summer project on building two key elements required for our desired organism:

An inducible secretion system
A biological pH sensor limiting this secretion system to the stomach

The pH system would sense the pH change when the probiotic organism leaves the stomach and prompt apoptosis to occur. We are confident that our two systems can be built in time to present to the iGEM community.

Team:UC Davis

From 2009.igem.org

Overview