Biophysical Models of Bacterial Growth

Introduction

Biology operates in a dynamic, changing environment, with fluctuations occurring over many time and length scales. Microorganisms are capable of duplicating themselves accurately over a short time in this noisy environment. This self-replication, known as the “cell cycle,” must be tightly regulated in order for replication to be efficient.

Key Processes

Key processes such as:

1. Growth (both of volume and biomass)
2. Division
3. DNA replication

must be coordinated. What biophysical cues are measured by the cell and what feedback is utilized to achieve this tight control is a fundamental, open, and inherently interdisciplinary question.

Project Goal

The goal of this proposal is to build integrated models which can account for the simultaneous regulation of multiple cellular traits and quantitatively account for the coupling between the various cellular processes.

Modeling Approach

We will consider coarse-grained models that operate on:

• Long timescales – the coupling of DNA replication, gene expression, and cell division
• Short timescales – associated with water flow and ion transport across the membrane

Building on our expertise in the physics of stochastic processes, we will develop biophysical models that explain how microbes deal with fluctuations.

Analysis Tools

We will develop new analysis tools that will enable us to learn from fluctuations, in particular through the powerful methodology of causal inference, which has not been previously applied in this context.

Implications of Variability

The models will allow us to study the implications of variability on population growth and fitness, and elucidate the design principles involved. Taken together, these models will take us toward comprehensive and predictive biophysical models of bacterial growth.