Project Reference: TRG27-ENG-SB1

Project title: Inside the Cell: Systems Biology of Antibiotic Accumulation

Project outline

Why do some bacterial cells survive an antibiotic treatment that kills their genetically identical neighbours? One important but poorly understood part of the answer may lie in how much antibiotic actually reaches and remains inside each cell. Intracellular drug concentration is not simply dictated by the dose outside the cell: it emerges dynamically from drug entry, active removal, interactions with cellular targets, and the physiological state of the bacterium itself.

This project will use the antibiotic tetracycline as a model system to uncover the principles governing this hidden layer of antibiotic response. The student will combine single-cell experiments with mathematical modelling to determine how influx, efflux and cellular physiology interact to shape antibiotic accumulation over time.

Time-lapse microscopy and microfluidics will be used to follow antibiotic accumulation together with key features of cellular state in individual bacteria. These measurements will inform mathematical models of intracellular drug dynamics, while model predictions will identify the most informative experiments and targeted perturbations to perform next. This iterative cycle between experiment and modelling will allow the student to distinguish competing mechanisms and identify the processes responsible for cell-to-cell variability.

By revealing how bacterial cells dynamically control the drug concentrations they experience, the project aims to establish a quantitative framework for understanding why antibiotic exposure produces such different outcomes from cell to cell. More broadly, it will help bridge the gap between the antibiotic concentration we administer and the concentration that actually reaches its target inside an individual bacterium - an essential step towards a more predictive understanding of antimicrobial treatment.

Principal Supervisor

Professor Somenath Bakshi

Email address: sb2330@cam.ac.uk

Department / Partner Institute: Engineering

Website: https://www.bakshilab.net/

BBSRC strategic theme

Bioscience for an integrated understanding of health