Team:Evry

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<h2 align='center'>Abstract</h2>
<h2 align='center'>Abstract</h2>
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Our starting idea was a very simple disease: hemochromatosis. The consequences are chronic insufficiencies due to an iron overload in blood. The only working treatment was regular bloodletting and this appeared as a very archaic technique which contrasted with the actual advances in the medical field. After deeper research on the disease, we figured out that the symptoms of the disease are the consequence of an iron overabsorption from the intestins. At this very moment, we came to the idea to design a bacterium able to chelate iron in the intestins. The challenge is huge, albeit rather unfeasable. However, after finding out that Escherichia coli naturally produces siderophores, iron chelators secreted in the environment, we then chose to make it our final subject for this iGEM 2013.
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This year we choose to develop a project which deals with hematologic diseases, which concerns more precisely diseases with an iron overload disorder. Among those type of diseases, there are the hereditary hemochromatosis and hemosiderosis. In the case of hereditary hemochromatosis, the iron overload disorder is a direct consequence of the disease. While in the hemosiderosis this consequence is due to a metabolic perturbation.
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Today the iron overload can be treated by bloodletting in the case of the hemochromatosis but it cannot be used in the case of hemosiderosis because patients suffer of anaemia. In our project we want to solve this problem acting directly in the iron absorption source, in the intestines.
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Bloodletting consists of the withdrawal of blood for therapeutic purposes. It is one of the oldest medical techniques and is nowadays abandonned. However in hematology, bloodletting (also known as phlebotomy) seems to remain the only reliable solution to cure hemochromatosis and thalassemia. Both are genetic diseases diseases and consist of an iron overload. The iron ion is toxic due to its oxidative potential, and thus, has a very smooth regulation mechanism. In fact, the organism only absorbs the required amount of iron from the intestins. The pathogenic mechanism is due to a seemingly low iron rate in the organism and permanantly activate the absorption system by the instestins, thus leading to an iron overload. The consequences are mainly chronic insufficiencies (renal, hepatic, cardiac, ...). Despite the true efficiency of bloodletting, some patients cannot bear this archaic way of treating their disease. As a consequence, we decided to design an Escherichia coli capable of chelating iron in the intestins: Iron Coli. The bacterium will lower the amount of iron absorbed by the duodenum and reduce the frequency of bloodlettings. Also, certain patients are treated with iron chelators which have a lot of side effects. The reduction of iron absorption by Iron Coli will allow lower drug concentrations and improve the patient's comfort.
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Using the Ferric Uptake Regulation system, we engineered a bacterium giving it the ability to produce siderophores (iron chelator) in response of iron. In order to limit the iron overload in the patient, this bacterium would be placed in the intestines.
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Revision as of 16:07, 7 August 2013

Welcome to the Iron coli Project

Abstract

This year we choose to develop a project which deals with hematologic diseases, which concerns more precisely diseases with an iron overload disorder. Among those type of diseases, there are the hereditary hemochromatosis and hemosiderosis. In the case of hereditary hemochromatosis, the iron overload disorder is a direct consequence of the disease. While in the hemosiderosis this consequence is due to a metabolic perturbation.
Today the iron overload can be treated by bloodletting in the case of the hemochromatosis but it cannot be used in the case of hemosiderosis because patients suffer of anaemia. In our project we want to solve this problem acting directly in the iron absorption source, in the intestines.
Using the Ferric Uptake Regulation system, we engineered a bacterium giving it the ability to produce siderophores (iron chelator) in response of iron. In order to limit the iron overload in the patient, this bacterium would be placed in the intestines.

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