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Single-cell nanopore sequencing to understand mechanisms of antibiotic resistance

Primary Supervisor: Dr Josh Quick, School of Biosciences

Secondary supervisor: Jess Blair

PhD project title: Single-cell nanopore sequencing to understand mechanisms of antibiotic resistance

University of Registration: University of Birmingham

Project outline:

Antimicrobial resistance is a serious public health concern as the frequency of antibiotic resistant infections is increasing. A scarcity of new antibiotics means we urgently need to protect the effectiveness of existing drugs by reducing antibiotic usage or risk the widespread occurrence of untreatable infections. One possible solution is to use real-time sequencing methods to rapidly identify infections and predict antibiotic susceptibility in a near-patient setting.

In this project we will explore the use of cutting-edge sequencing technology to predict antibiotic resistance by changes in gene expression levels. We will expose microbial cultures to sublethal doses of antibiotics before using single/double droplet emulsions, developed for single-cell genome sequencing, to encapsulate individual cells for RNA sequencing. By comparing the expression profile of exposed and unexposed cells we will determine if resistance to different classes of antibiotics can be predicted over a short period of exposure. You will utilise many cutting edge genomic technologies including Illumina/nanopore sequencing, robotic liquid handlers, microfluidic apparatus, 3D printing and cloud computing.

This study will provide insights into whether real-time molecular testing will someday supplant current methods such as broth microdilution in order to determine antibiotic resistance and could lead to more effective early antibiotic therapy and reduce the dependence on broad-spectrum therapies and spread of antibiotic resistance. It may also provide insights into evolution and the underlying mechanisms of antibiotic resistance.

BBSRC Strategic Research Priority: Sustainable Agriculture and Food: Animal Health and Welfare & Microbial Food Safety & Understanding the Rules of Life: Microbiology

Techniques that will be undertaken during the project:

  • Nanopore library preparation and sequencing
  • Robotic liquid handling
  • Single-cell approaches including microfluidic droplet generation
  • Bioinformatics and data analysis including Linux and Python programming

Contact: Dr Josh Quick, University of Birmingham