Team:Edinburgh OG

PhagED: a molecular toolkit to re-sensitise ESKAPE pathogens

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 baumanii

Modular molecular toolkit for re-sensitisation of antibiotic-resistant pathogens using CRISPR delivered by a two-phage system.

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ABOUT 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

TAKE A CLOSER LOOK

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

Developing the lysoenic lambda phage carrying the FnCpf1 CRISPR system.

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

Developing the lysogenic P1 phage carrying spCas9 CRISPR system.

Ti He

MSc Biotechnology

Developing the lysogenic lambda phage carring saCas9 CRISPR system.

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 P1 lysogenic phage with CRISPR-SaCas9 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 P1 lysogenic phage with CRISPR-Cpf1 system to target resistance gene fragments.


Owen Yeung

MSc Synthetic Biology & Biotechnology

Developing the lysoenic lambda phage carrying the SpCas9 CRISPR system.

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.

DO YOU WANT TO HELP US TURN IT INTO REALITY?

We will be more than happy to accept any kind of support from you either in cash or as free/discounted services or consumables.

    • Bronze

      £ 500
      • Logo on website
      • Recognition on social media
      • Logo on t-shirts
      • Logo on media content
      • Logo on presentation
      • Logo on official poster
    • Silver

      £ 1,000
      • Logo on website
      • Recognition on social media
      • Logo on t-shirts
      • Logo on media content
      • Logo on presentation
      • Logo on official poster
    • Gold

      £ 2,000
      • Logo on website
      • Recognition on social media
      • Logo on t-shirts
      • Logo on media content
      • Logo on presentation
      • Logo on official poster
    • Platinum

      £ 2,500
      • Logo on website
      • Recognition on social media
      • Logo on t-shirts
      • Logo on media content
      • Logo on presentation
      • Logo on official poster

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