Project 4A: Diauxic growth in bacteria
Project assignment
Develop a coarse-grained model that (i) includes a representation of known regulatory mechanisms underlying carbon catabolite repression (CCR) and (ii) reproduces quantitative data and qualitative observations on diauxic growth.
Biological question to be answered
Which mechanisms are necessary for bringing about diauxic growth?
Known regulatory mechanisms to be included: enzyme induction, inducer exclusion, and global regulation of gene expression by metabolic signal (cAMP). Quantitative data and qualitative observations to account for:
- Curves of glucose-lactose diauxie in standard batch conditions with glucose and lactose;
- Curves of glucose-lactose diauxie in a batch experiment with a glucose pulse and a batch experiment with a high starting concentration of lactose enzymes;
- No growth in the absence of glucose and lactose.
Model structure
Environment described by concentrations of biomass (B, gDW/L), preferred substrate (G, mmol/L) and secondary substrate (L, mmol/L) in the bioreactor of constant volume.
The growth rate is denoted by \(\mu\) (1/h), while \(v_G\) and \(v_L\) (mmol/(gDW L)) correspond to the uptake rates of glucose and lactose, respectively. In the project, we are going to build a model of the growing bacterial population in this environment.
Available data
Csv files of the three experiments described above. The data originates from K. Bettenbrock et al. A quantitative approach to catabolite repression in Escherichia coli. J Biol Chem. 2006;281:2578–84. Additional comments:
- In the pulse experiment, the glucose pulse occurs at 5 h and LacZ activity is a proxy for the LacZ concentration;
- In the batch experiment with a high starting concentration of lactose enzymes, glucose is depleted at 3 h and LacZ activity is a proxy for the LacZ concentration.