Summary
We have recently defined the critical sequential steps involved in the evolution of environmental bacterial into specialised lung pathogens for mycobacteria (Science 2016, Science 2021, Nature Micro 2021, Nature Micro 2022) and Pseudomonas aeruginosa (Science 2024).
Through this work we have identified networks of genes that are repeatedly mutated during lung adaptation and shown that certain patterns are associated with bacterial specialisation for different types of underlying lung disease.
Project aims
Our proposal now is to:
- Reconstitute evolutional trajectories in isogenic bacteria using novel base editing methods to understand functional consequences of host adaptation in in vitro, ex vivo, and in vivo infections models;
- Construct gene regulatory networks (using perturb-seq approaches) to understand transcriptional rewiring during pathogenic evolution;
- Explore how tissue immunity, inflammation, and metabolism influence the success of specific evolutionary trajectories using spatial transcriptomics and metabolomics of chronically-infected excised human lungs
Contact details
Professor Andres Floto - arf27@cam.ac.uk
Opportunities
This project is open to applicants who want to do a:
- PhD