Team:Evry/Modeling

From 2013.igem.org

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<h2>Introduction:</h2>
<h2>Introduction:</h2>
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<p>The modeling part heavily influenced the early stages of the project. In fact, before any biological result appeared, our simulations gave the preliminar hints to the team in the strategy to adopt for the iron-sensing inverter and the strategy to opt in the design of the capsule.<br/>
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In the begining, the team's goal was to chelate iron in the duodenum, using bacteria that would flush through the duodenum. We made a <b>qualitative model</b> showing promising conclusions, but when we ran a <b>metabolic model</b>, we realised that the siderophore production is a very slow phenomenon. It is thus impossible to chelate the iron using a flush-strategy.<br/>
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Then came the idea of a gel containing our bacteria, that would stick to the very begining of the Jejunum's wall. Among all the safety issues this strategy creates, the most important question that raised at this point was : "can our bacteria produce siderophores like crazy and still survive long enough to chelate a significant quantity of iron?". A <b>Flux Balance Analysis</b> helped solving this question.
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In the begining, our goal was to chelate iron in the duodenum, using bacteria that would flush through the duodenum and produce the siderophores. The aim was to predict the sufficient quantity of produced siderophores to reduce the iron intestinal absorption. We first had in mind a flush strategy, meaning we prioritized an approach where the bacteria would start their iron sensing and siderophore production before entering the duodenum. This <b>qualitative model</b> allowed us also to calculate how much bacteria where required to reduce by 50% de iron absorption. The conclusions were promising, encouraging and comforting regarding our strategy choice. Right afterwards, the aim was to detail the delay of siderophore production for a given bacterial production through a <b>metabolic model</b>. This approach gave us more detail about timings. Unfortunately, the conclusions were in contradiction with the qualitative model because the delay is to big to be compatible with a flush strategy. This conclusion greatly influenced on the biological part, especially in the design of the capsule. Because the iron absorption is split among the duodenum (60%) and the jejunum (40%), we decided to enhance growth in the proximal area of the jejunum. This is also why we chose to deliver a sticky gel with our bacteria and optimize its growth. As a final part in the modeling, we also wanted to know how much siderophore can be produced and how we can improve this. We answered this with a <b>Flux model</b> with a flux balance analysis approach.
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Revision as of 15:27, 4 October 2013

Iron coli project

Model overview

Introduction:

In the begining, our goal was to chelate iron in the duodenum, using bacteria that would flush through the duodenum and produce the siderophores. The aim was to predict the sufficient quantity of produced siderophores to reduce the iron intestinal absorption. We first had in mind a flush strategy, meaning we prioritized an approach where the bacteria would start their iron sensing and siderophore production before entering the duodenum. This qualitative model allowed us also to calculate how much bacteria where required to reduce by 50% de iron absorption. The conclusions were promising, encouraging and comforting regarding our strategy choice. Right afterwards, the aim was to detail the delay of siderophore production for a given bacterial production through a metabolic model. This approach gave us more detail about timings. Unfortunately, the conclusions were in contradiction with the qualitative model because the delay is to big to be compatible with a flush strategy. This conclusion greatly influenced on the biological part, especially in the design of the capsule. Because the iron absorption is split among the duodenum (60%) and the jejunum (40%), we decided to enhance growth in the proximal area of the jejunum. This is also why we chose to deliver a sticky gel with our bacteria and optimize its growth. As a final part in the modeling, we also wanted to know how much siderophore can be produced and how we can improve this. We answered this with a Flux model with a flux balance analysis approach.

Modeling Parts:

duodénum zoom sur les parois bactérie FBA

Tools:

When working on a scientific project, it is always good to properly define and clarify the tools we are going to use. These pages contain the theorical background for our models:

Programming environment logistic functions Chemical reasoning