Individual-based modeling of Plasmodium falciparum erythrocyte infection in in vitro cultures

Author: Jordi Ferrer Savall June 2010

Directors: Daniel López and Joaquim Valls
Department: Physics and Nuclear engineering
Research group: MOSIMBIO (Discrete Modeling and Simulation of Biological Systems)
Defense date: 21st of June 2010

The PHD thesis of Jordi Ferrer, “Individual-based modeling of Plasmodium falciparum erythrocyte infection in in vitro cultures” presents a theoretical approximation to the process of infection to red blood cells in vitro by Plasmodium falciparum, one of the parasitic protozoa that causes malaria.

The project focuses in the development of a Computational model with the adequate complexity needed to approach the specific problems identified by the experts on the field, and includes also the formulation of simulation algorithms and the design of experimental protocols.

Nowadays, malaria still affects half of the human population and causes approximately 1 million deaths per year all around the world. Its eradication implies a challenge for all human beings and more concretely, for the scientific community. The in vitro culture of the parasite is essential for the development of new medicines. The current culture methods are based in the heuristic gained during the last 30 years and requires some improvements.

The experimental work of the experts on malaria is complemented with the modeling and simulation, which allows testing the preestablished assumptions, the observed phenomena comprehension and the improvement of the current culturing methods. Therefore, it is necessary to establish and develop tools that promote and allow the creation, analysis and exchange of models with groups that are working on malaria from different perspectives. This PHD thesis has focused on a modeling based in individuals (IbM) and oriented to the reproduction of multiple patterns (PoM). The model has been developed applying the ODD, an standard protocol that belongs to the theoretical ecology field, and has been adapted to the representation of the microbial communities. In addition, thermodynamic related concepts have been applied in order to understand the apparition of microscopic patterns from the population structure.

Applying all this information, the application of the model and simulator INDISIMRBC is obtained, which has demonstrate to be a good tool in order to improve the comprehension of the studied cultures. INDISIM-RBC defines a group of rules which rule the behavior of each cell and the interactions with the other cells and the immediate surroundings. Taking as a reference these rules, and taking in consideration a certain diversity within the population and a certain randomness degree in the individual processes, the simulations explicitly show the emerging behavior of the system as a whole. The work carried out about malaria has been compared with a research done by a research group in relation with other microbial communities in order to develop conceptual tools with general applicability.

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