Deciphering Streptococcus dysgalactiae subsp. equisimilis Population Genomics and Host-Pathogen Interactions using Advanced 3D Tissue Engineered Infection Models

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Streptococcus dysgalactiae subspecies equisimilis (SDSE) is an emerging human pathogen responsible for a diverse range of infections, from mild skin and throat infections to severe invasive diseases. Understanding the genetic diversity within SDSE populations and the intricate mechanisms it employs to interact with host tissues is crucial for developing effective prevention and treatment strategies.

This innovative PhD project offers a unique opportunity to investigate SDSE pathogenesis by combining cutting-edge approaches:

1. Population Genomics: You will utilize whole-genome sequencing and bioinformatic analysis to: * Characterize the genetic diversity and evolutionary relationships within a collection of clinical SDSE isolates. * Identify genetic determinants associated with specific infection types, virulence factors, and antimicrobial resistance. * Explore the population structure and transmission dynamics of SDSE in the human population.

2. 3D Tissue Engineered Models: You will employ advanced 3D in vitro models of: Human Skin: To investigate SDSE interactions with the skin barrier, biofilm formation, and the host immune response during skin infections (e.g., cellulitis, erysipelas). Human Tonsil: To study SDSE colonization, invasion, and interactions with the tonsillar epithelium, mimicking pharyngitis and potential progression to more severe disease.

Alongside undertaking these novel approaches, genetic manipulation and other lab-based phenotypic work will be used to comprehensively characterise SDSE as a human pathogen, revealing potential new therapeutic and vaccine possibilities. 

You will gain hands-on experience in:

•    Bacterial culture and manipulation

•    Bioinformatic analysis, including genome assembly, annotation, phylogenetics, and comparative genomics

•    Development and maintenance of 3D tissue engineered models

•    Advanced microscopy techniques (e.g., confocal microscopy)

•    Cell culture and infection assays

•    Molecular biology techniques (e.g., PCR, qPCR, ELISA)

You will receive interdisciplinary training that will prepare you for a range of career paths, within and beyond academia.

•    You will join a collaborative and diverse research group that focuses on streptococcal biology and host-pathogen interactions.