Project Reference: TRG27-SAN-JB1

Project title: Genomic Evolution and Antimicrobial Adaptation in Mycobacterium abscessus

Project outline

Mycobacterium abscessus is an environmental mycobacterium and human pathogen. Its persistence across ecological niches, capacity to cause chronic infection and tolerance of multidrug treatment are influenced by variation in its core and accessory genomes. However, the genomic mechanisms driving this diversity, and the extent to which evolutionary responses are shared across subspecies and globally circulating lineages, remain unclear.

This PhD will investigate the population genomics, evolutionary biology and antimicrobial adaptation of M. abscessus. It will combine newly generated whole-genome sequencing data from the FORMaT trial, involving sites in Australia, Singapore, Israel, the UK, Denmark and Taiwan, with existing international public datasets. FORMaT will provide valuable longitudinal samples, enabling detection of evolutionary change during antimicrobial treatment.

The project will:

  • characterise subspecies, population structure and genomic diversity
  • identify variants and pathways associated with intrinsic and acquired antimicrobial resistance
  • determine how different antibiotic environments shape within-host evolution
  • detect convergent and parallel evolution across independently treated populations

The student will use bioinformatic and statistical methods including genome assembly, variant calling, phylogenetics and pangenome analysis. Serial isolates will be analysed to identify mutations repeatedly selected during antimicrobial exposure, and genomic variation will be integrated with susceptibility data to investigate genotype–phenotype relationships.

The project will provide fundamental insight into how bacterial populations adapt to sustained antimicrobial pressure. Applicants should have a background in biology, microbiology or genomics. Training will be provided in bacterial genomics, evolutionary analysis and phylogenetics.

Principal Supervisor

Dr Josephine Bryant

Email address: jb31@sanger.ac.uk

Department / Partner Institute: Sanger Institute

Website: https://www.sanger.ac.uk/person/bryant-josie/

BBSRC strategic theme

Understanding the rules of life