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Project properties |
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| Title | Kinetic modelling of cofactors in E. coli in anoxic conditions |
| Group | Systems and Synthetic Biology |
| Project type | thesis |
| Credits | 36 |
| Supervisor(s) | Claudia de Buck, Prof. Dr Maria Suarez Diez. |
| Examiner(s) | Prof. Maria Suarez Diez (SSB) Dr. Rob Smith |
| Contact info | robert1.smith@wur.nl |
| Begin date | 2024/02/09 |
| End date | |
| Description | To understand and study microbial metabolism there have been many efforts to represent microbial reaction networks as computational models. Escherichia. coli is one of the organisms for which these efforts have been most intensive, since E. coli is one of the model organisms in the field of biotechnology and metabolic engineering. Kinetic models represent an important class of metabolic models. They consists of a set of ordinary differential equations (ODEs) and they allow for the simulation of the intracellular metabolite concentrations over time. Recent efforts have resulted in several versions of kinetic E. coli models (Kurata & Sugimoto, 2018; Matsuoka & Kurata, 2017; Millard et al., 2017). However, the exact implementation of each model is different, which means that different models are suited for answering different biological questions. Next to that some models have been developed for simulations in chemostats (with fixed dilution rate converging to a steady state), while others are also suited for batch (with a dynamic glucose uptake rate).
During my PhD project I am studying the energy metabolism of E. coli, in particular the role of different cofactors (NAD(P)H) in oxic and anoxic conditions. Currently, there is no available E. coli kinetic model that allows the simulation of the cofactor-concentrations in both batch and chemostat in anoxic conditions. There are, however, several models that fulfil a few of these requirements. The main goal of this thesis project is therefore to investigate ways of combining the information of several E. coli kinetic models into one model that meets (most of) the requirements mentioned before. During this thesis you will acquire an in-depth understanding of E. coli kinetic models, as you will modify and simulate models by developing scripts in python. Moreover, to support your choices for model modifications related to cofactor metabolism, you will study relevant literature on redox metabolism and use protein/gene databases to obtain overview of the reactions that involve cofactors. Model simulation is supported by specific python-packages (Choi et al., 2018). You will also gain experience with version control in git and some basic experience with linux, as large simulations will be executed on the linux-server hosted by SSB. References Choi, K., Medley, J. K., König, M., Stocking, K., Smith, L., Gu, S., & Sauro, H. M. (2018). Tellurium: An Extensible Python-based Modeling Environment for Systems and Synthetic Biology. Bio Systems, 171, 74. https://doi.org/10.1016/J.BIOSYSTEMS.2018.07.006 Kurata, H., & Sugimoto, Y. (2018). Improved kinetic model of Escherichia coli central carbon metabolism in batch and continuous cultures. Journal of Bioscience and Bioengineering, 125(2), 251–257. https://doi.org/10.1016/j.jbiosc.2017.09.005 Matsuoka, Y., & Kurata, H. (2017). Modeling and simulation of the redox regulation of the metabolism in Escherichia coli at different oxygen concentrations. Biotechnology for Biofuels, 10(1), 1–15. https://doi.org/10.1186/S13068-017-0867-0/FIGURES/6 Millard, P., Smallbone, K., & Mendes, P. (2017). Metabolic regulation is sufficient for global and robust coordination of glucose uptake, catabolism, energy production and growth in Escherichia coli. PLoS Computational Biology, 13(2). https://doi.org/10.1371/journal.pcbi.1005396 |
| Used skills | Metabolic modelling with kinetic models; in depth understanding (anaerobic) cofactor metabolism in E. coli. |
| Requirements | Python, ideally some experience with kinetic modelling with ODEs (SSB-31806). |