PhD Studentship: Mechanistic Modelling of Biofilm-Induced Host-Cell Damage

Biofilm-associated infections can cause persistent damage to surrounding tissues, but the mechanisms linking biofilm development to host-cell injury remain poorly quantified. Biofilm growth, nutrient availability, bacterial toxins, oxidative stress, and inflammatory signalling evolve together and may contribute differently to DNA damage, repair failure, and cell death. Experiments can measure many of these responses, but they cannot easily determine which mechanisms are dominant or how they interact across space and time. This project will therefore develop a mechanistic mathematical framework that integrates experimental observations, identifies the processes driving host-cell damage, and quantifies the uncertainty in those conclusions.

The PhD will pursue four integrated aims:

1. Mechanistic modelling: develop a mathematical model linking biofilm growth and structure with nutrient transport, bacterial toxins, reactive oxygen species, inflammatory signalling, DNA damage, repair and host-cell viability.
2. Computational simulation: develop efficient numerical methods to simulate how these interacting processes evolve across space and time, including changing biofilm structure and local biochemical gradients.
3. Parameter inference and mechanism identification: use experimental data to estimate hidden biological parameters, quantify uncertainty, and determine which mechanisms are supported by the observations.
4. Prediction and experimental guidance: use the calibrated model to identify informative measurements and sampling conditions, distinguish competing damage pathways, and predict responses to selected therapeutic interventions. These predictions will be tested using independent experiments.

The project will deliver an experimentally validated framework for explaining how biofilms generate host-cell injury and for identifying which biological mechanisms should be targeted to reduce damage while maintaining effective bacterial control.

Funding notes:

All details regarding the sources of funding and eligibility criteria can be found at this link.

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