Kreft Lab Research Themes

Individual-based modelling of microorganisms

The focus of our research has revolved around Individual-based Modelling but we have also used other mathematical models for comparison and in cases where simpler models are more appropriate. Experimental validation is the second branch of our activities.

Individual-based Modelling has been used for many decades studying macrobes such as trees, fish, and birds, becoming more popular in the 1990's.

I decided that microbes also deserve to be treated as individuals and started adopting IbM for microbes in 1997. At the time I thought that individuality mainly arises from differences in the environment and the history of environmental conditions experienced by the cells. Only more recently did we learn that noise in gene expression combined with e.g. positive feedback can lead to individual cells becoming upregulated by chance when neighbouring sisters, genetically identical and in the same environment, would remain downregulated (bistability). Using IbM for microbes has become more mainstream in recent years, and I am happy to have contributed to this success.

The individual-based approach takes advantage of the modular self-organisation of populations and communities by describing such populations or communities in terms of their parts, the individual organisms. The population properties emerge as a result of the actions and interactions of these parts with each other and with the environment. The higher level of organisation therefore is not at all described in such a bottom-up model.

A brief history of software development

The first step was to prove that IbM is feasible for bacteria by writing a model of Escherichia coli colony development, dubbed BacSim.

The next step was the extension of BacSim to multi-species, multi-substrate biofilms. The biofilm version of BacSim was then extended by the inclusion of Extracellular Polymeric Substance (EPS) production as a further process.

Further development of the software aimed to merge code developed by my colleagues Cristian Picioreanu and Joao Xavier (both at TU Delft at the time) with BacSim and produce a more general and user-friendly software, which we called iDynoMiCS. iDynoMiCS continues to be improved, with the addition of more features, processes, removal of bugs, and improvements of the documentation. And it is the basis for the development of eGUT, which has just started.

A brief history of the application of IbM to fundamental or applied research questions

Some of the interesting applications of IbM are briefly explained in separate sections: the division of labour in nitrification, the evolution of altruism in biofilms, the infection of eggs by Salmonella, and the transfer of broad or narrow host range plasmids in chemostats and biofilms. More research is described in our publications.

University of Birmingham | Centre for Systems Biology | Institute of Microbiology and Infection | School of Biosciences | Find The Lab