Difference between revisions of "Team:Oxford/Description"

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<h1>Project Summary</h1>
 
<h1>Project Summary</h1>

Revision as of 11:07, 23 May 2015

Team Oxford

Project Summary



We are interested in developing an autonomous antibacterial system using an E. coli chassis through synthetic biology. Our antibacterial strategy involves a two-step mechanism:

    i) Destroy the bacterial biofilm which confers the bacteria encased within significantly increased resilience against antibiotics.

    ii) Destroy the liberated bacteria by directly lysing their cell walls.

We will be experimenting with antibacterial action against E. coli and P. aeruginosa.


Antibiofilm action

The cartoon above shows two of the major structural components of bacterial biofilms - extracellular polymeric substance (a.k.a. EPS, in blue) and extracellular DNA (in pink). The Doctor. coli system will release the following enzymes targeting these structural components:

    Dispersin B Destroys E. coli biofilms by hydrolysing beta-1,6-N-acetyl-D-glucosamine, which is the major EPS in E. coli biofilms
    Thermonuclease Also commonly known as staphylococcal nuclease, this enzyme can destroy P. aeruginosa biofilms by hydrolysing its extracellular DNA


Antibacterial action

Doctor. coli will release "artilysins", which is a class of combination biomolecules made by fusing endolysins (phage-derived enzymes that hydrolyse bacterial cell walls) with SMAP-29 (a transporter peptide that brings the complex through the bacterial outer membrane such that it can get in contact with the cell wall). Endolysins are species-selective in terms of the type of cell wall which they hydrolyse, and as such Doctor. coli will be making two different artilysins:

    Art-175 An artilysin specific for P. aeruginosa comprising endolysin KZ-144 and SMAP-29, invented in 2013
    Art-E An E. coli-specific artilysin, comprising T4 endolysin and SMAP-29, conceptualized and designed by our team


Overall design

We intend to construct two variations of Doctor. coli