Tesis doctoral de Jordi Ferrer Savall
Malaria is still a major burden that causes approximately one million deaths annually worldwide. Its eradication supposes a great challenge to the humanity and to the scientific community, in particular. In vitro cultivation of the parasite is essential for the development of new drugs. Current culture methods are based on heuristics and demand for specific improvements. the present thesis is a theoretical approach to in vitro cultivation of the protozoan parasite plasmodium falciparum infecting human red blood cells. It mainly focuses on the process of building a model of appropriate complexity to deal with the specific demands above mentioned, but it also includes the formulation and implementation of algorithms, and the design and execution of experimental trials. this kind of work requires multidisciplinary collaboration: the insight of the experts in malaria research is complemented with modeling and simulation, which allows for checking settled assumptions, increasing the understanding on the system and improving the current culturing methods. the use of tools for building, analyzing and sharing models is an imperative to this end. In this thesis, pattern-oriented modeling (pom) has been adopted as the most appropriate way for raising of models and the odd protocol (objectives, design concepts and details) has been proposed as the standard tool for communicating them. individual-based modeling (ibm) has been used to tackle malaria culture systems. Ibms define a set of rules governing each cell, its interactions with others and with its immediate surroundings. From this set of rules, and taking into account diversity within the population and a certain degree of randomness in the individual processes, ibms explicitly show the emerging behavior of the system as a whole. Methods from statistical thermodynamics have been applied to understand the emergence of macroscopic patterns from the population structure (e.G. Distribution of infection stages among infected red blood cells). the research resulted in the development of the model and simulator indisim-rbc, which has proved to be a good tool to improve understanding of the cultures under study. It is a mechanistically rich individual-based model and it quantitatively reproduces and predicts several patterns observed in real cultures at different levels of description. we demonstrated that indisim-rbc can be used to study in detail several aspects of malaria cultivation that remained unclear, as well as to perform virtual experiments. Consequently, it can be used to open novel lines of research and to examine potential experimental techniques. Indisim-rbc has also been used to improve the current experimental culturing protocols in static cultivation by obtaining the optimal geometry of the hematocrit layer and subcultivation periods in the continuous cultures. this study on malaria has been compared to the research carried out by the group regarding other microbial communities. Thereby studying general emerging properties of microbial systems in general, with regard to the effect of cell individuality, heterogeneity and diversity, the local nature of interactions; and biological and spatial complexity. In doing so, the acquired holistic view has been used to develop tools that allow for a better characterization and study of the infection process, in particular.
Datos académicos de la tesis doctoral «Individual-based modeling of plasmodium falciparum erythrocyte infection in in vitro cultures«
- Título de la tesis: Individual-based modeling of plasmodium falciparum erythrocyte infection in in vitro cultures
- Autor: Jordi Ferrer Savall
- Universidad: Politécnica de catalunya
- Fecha de lectura de la tesis: 21/06/2010
Dirección y tribunal
- Director de la tesis
- Daniel López Codina
- Tribunal
- Presidente del tribunal: josep Vives rego
- domingo Gargallo viola (vocal)
- simone Ladeia andrade (vocal)
- moises Silbert (vocal)