Team:Edinburgh OG
Antibiotic revolution: a molecular toolkit to re-sensitise
Methycillin resistant S.aureus (MRSA)
Vancomycin resistant S.aureus (VRSA)
Klebsiella pneumoniae
Pseudomonas aeruginosa
Enterococcus faecalis/faecium
Acinetobacter baumannii
Modular molecular toolkit for re-sensitisation of antibiotic-resistant pathogens using CRISPR delivered by a two-phage system.
Read moreABOUT PhagED
The threat posed by antibiotic resistant bacteria is a pressing issue which must be addressed. It is difficult and expensive to develop new antibiotics, so our project is designed to make currently available antibiotics useful again. Our aim is to create a toolkit to re-sensitise pathogens to antibiotics using CRISPR and a two-phage system, based on work by Yosef et al. (2015, doi:10.1073/pnas.1500107112). An engineered lysogenic phage will transfer a CRISPR system to its host bacterium, designed to cleave resistance genes and also confer protection from an engineered lytic phage. When this lytic phage is added to the population, it kills any bacteria that have not been successfully re-sensitised. We chose to target genes found in the highly-resistant ESKAPE pathogens, and worked with 4 different phages - P1, lambda, T4 and T7. Our system was modelled in silico and tested empirically on a specially designed E. coli testing platform.
Figure: Yosef et al., 2015
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Project
Get to know PhagED better.
Parts
Blocks of DNA that we've used.
Safety
Safety always comes first.
Human Practices
How does PhagED fit into the context of our lives?
Meet The Team
Filippo Abbondanza
MSc Synthetic Biology & Biotechnology
Engineering the lysogenic lambda phage with a CRISPR system to target resistance gene fragments.
Erin Corbett
MSc Synthetic Biology & Biotechnology
Engineering E. coli to create our mock pathogen testing platform, and engineering the lytic T7 phage.
Yunqi He
MSc Biochemistry
Engineering the lysogenic P1 phage with a CRISPR system to target resistance gene fragments.
Ti He
MSc Biotechnology
Engineering the lysogenic lambda phage with a CRISPR system to target resistance gene fragments.
Lydia Mapstone
MSc Synthetic Biology & Biotechnology
Engineering E. coli to create our mock pathogen testing platform and engineering the lytic T4 phage using BRED.
Yuri Matsueda
MSc Biotechnology
Engineering the lysogenic P1 phage with a CRISPR system to target resistance gene fragments.
Anton Puzorjov
MSc Bioinformatics
Building a model of bacteria-phage interactions in two-step re-sensitisation combining both lysogenic and lytic phages.
Yating Wang
MSc Drug Discovery & Translational Biology
Engineering the lysogenic phage P1 with a CRISPR system to target resistance gene fragments.
Owen Yeung
MSc Synthetic Biology & Biotechnology
Engineering the lysogenic lambda phage with a CRISPR system to target resistance gene fragments.
The Edinburgh_OG team members developed the iGEM project as part of our Masters dissertations at the University of Edinburgh. Due to academic requirements, the iGEM project, PhagED, was divided into individual sub-projects to allow the production of unique dissertations. Each of us completed a dissertation based on the work we did for iGEM, and these dissertations are available upon request.
Supervisors
Dr Elise Cachat
School of Biological Sciences
Academic supervisor.
Dr Heather Barker
School of Biological Sciences
Supervising lab work.
Holly Robertson-Dick
Industrial Liaison
Supervising iGEM administrative work.
Dr John White
School of Chemistry
Supervising phage work.
Dr Filippo Menolascina
School of Bioengineering
Supervising bacteria-phage modelling.
Dr Russell Brown
School of Biological Sciences
Supervising P1 phage construction.
Sponsors
We are very thankful to those who are helping us to make it happen.
