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Details of Grant 

EPSRC Reference: EP/R029822/1
Title: Physics of Bacterial Growth Control and Antibiotic Resistance
Principal Investigator: Banerjee, Dr S
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Department: Physics and Astronomy
Organisation: UCL
Scheme: New Investigator Award
Starts: 01 May 2018 Ends: 30 April 2020 Value (£): 216,297
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Panel History:
Panel DatePanel NameOutcome
24 Jan 2018 EPSRC Physical Sciences - January 2018 Announced
Summary on Grant Application Form
Living systems operate far from equilibrium, constantly consuming and dissipating energy to perform their defining functions of growth, replication, and adaptation to diverse environmental conditions. While the physical principles governing the dynamics of non-equilibrium systems have emerged over the past two decades, how these principles are realised for the regulation of vital biological processes remains poorly understood. The goal of the proposed research is to develop an in-depth physical understanding of the regulatory mechanisms controlling bacterial growth, shape development, and adaptive response to antibiotics.

Bacterial growth and shapes are determined by the cell wall, a rigid protein-based structure that can withstand high amounts of osmotic pressure while driving cell elongation. An outstanding challenge is to relate alterations in physical properties of the cell wall to adaptive shape changes and fitness control in bacteria. This is important for understanding how bacteria can recover their fitness for growth and division under antibiotic treatment that inhibit the cell wall growth machinery. We seek to address this challenge by proposing a novel framework in which theoretical modelling and experimental data are integrated to dissect how protein synthesis and stochastic cell cycle processes control robust growth and adaptive behaviour in single bacterial cells.

Using tools from statistical mechanics and soft matter physics, we will develop a quantitative model for growing cell wall structures that is coupled to stochastic decision-making processes for cell size and division control. We will extend this model to dissect how single bacterial cells harness the feedback between mechanical forces and biochemical reactions to adapt to growth inhibitory stresses. In particular, we will dissect the mechanisms of fitness recovery in rod-shaped bacterium under ribosome-targeting antibiotics that constitute a major class of clinically used antibacterial drugs. We will compare the theoretical model predictions against high-throughput experimental measurements of single bacterial shape and growth in normal and antibiotic-treated conditions. This integrated approach will allow us to determine the physical principles relating the speed and the accuracy of antibiotic adaptation to the energy consumption budget of a cell.

The outcome of this research will fundamentally advance our understanding of non-equilibrium physics of living systems by establishing a cost-performance tradeoff relation in adaptive biophysical processes. Furthermore we will directly address the physical impacts of antibacterial drugs on bacterial fitness at the single-cell level, which will have wide ranging implications for the development and design of new drugs that can effectively control the evolution of antibiotic resistance.
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