Team:Imperial College/Modelling beta-amyloid

From 2013.igem.org

Contents

Beta-Amyloid Degradation Model

Introduction

This is another degradation model we designed to help UCL 2013 iGEM team with their Beta-Amyloid Degradation Assays. Beta-Amyloid is known as the component of Amyloids Plaque in association with Alzheimer's disease (AD), in which the target of UCL iGEM this year. Matrix metallopeptidase 9 (MMP-9) was discovered to be able to degrade Beta-Amyloid that can be potentially used to cure Alzheimer's disease. The model provides simulations about how efficient is MMP-9 enzyme to degrade Beta-Amyloids.

Description

Objective

The Mathematical model was built in MATLAB extension Simbiology, it will predict how long will take to degrade a certain concentration of Beta-Amyloid by a given amount of MMP-9 enzyme. The simulation results can help UCL iGEM team to modify their assays in order to achieve better experimental results. The model can also be used to provide a preliminary prediction of degrading Amyloid Plaque in vivo.

Degradation Assays of UCL 2013 iGEM team

The details of the assays are here. There are three different substrates which are soluble aggregated β-amyloid (Aβ),aggregated β-amyloid (Aβ) fibrils 1-40 and aggregated β-amyloid (Aβ) fibrils 1-42. Here is the table that defines the initial concentrations of all substrates and the enzyme from the assays.

Species Concentration Units
soluble Aβ 25 uM
Aβ fibrils 1-40 200 uM
Aβ fibrils 1-42 100 uM
MMP-9 0.2 uM


Methods

The Model

BAmyloidModel.png

Explanation

Equations

We choose simple Michalis-Menten mechanism for Beta-Amyloid degradation. The ODEs for all substrate are:

Simple MM.png

The Km values here are for each substrate correspondingly whereas Kcat values are for MMP-9 in each assay.

Assumption

Although Matrix metallopeptidase 9 (MMP-9) is a well characterised enzyme, there is no clear kinetic data for degrading soluble Beta-Amyloids and its fibrils.

Results

Mmp9.png BA140.png BA142.png

Reference



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