부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jtbi.2007.05.030 Byline: Jordi Ferrer (a), Jaume Vidal (b), Clara Prats (a), Joaquim Valls (a), Esperanza Herreros (b), Daniel Lopez (a), Antoni Giro (a), Domingo Gargallo (b) Keywords: Individual-based model; Plasmodium falciparum; Simulation; Merozoite; Erythrocyte; In vitro culture; Malaria Abstract: Malaria is still one of the most fatal diseases in the world. Development of an effective treatment or vaccine requires the cultivation of the parasite that causes it: Plasmodium falciparum. Several methods for in vitro cultivation of P. falciparum infected erythrocytes have been successfully developed and described in the last 30 years. Some problems arising from the current harvests are the low parasitaemia and daily human supervision requirements. The lack of a suitable model for global culture behavior makes the assay of new methodologies a costly and tenuous task. In this paper we present a model and simulation tool for these systems. We use the INDividual DIScrete SIMulation protocol (INDISIM) to qualitatively reproduce the temporal evolution of the erythrocyte and merozoite populations. Whole system dynamics are inferred by setting the rules of behavior for each individual red blood cell, such as the nutrient uptake, metabolism and infection processes, as well as the properties and rules for the culture medium: composition, diffusion and external manipulation. We set the individual description parameters according to the values in published data, and allow population heterogeneity. Cells are arranged in a three-dimensional grid and the study is focused on the geometric constraints and physical design of experimental sets. Several published experimental cultures have been reproduced with computer simulations of this model, showing that the observed experimental behavior can be explained by means of individual interactions and statistical laws. Author Affiliation: (a) Departament de Fisica i Enginyeria Nuclear, Universitat Politecnica de Catalunya, Escola Superior d'Agricultura de Barcelona, Campus del Baix Llobregat, Avda. del Canal Olimpic s/n, 08029 Castelldefels, Spain (b) Drug Discovery Biology Group, Diseases of the Developing World Center, From GlaxoSimthKline, R&D, Tres Cantos, Madrid, Spain Article History: Received 23 November 2006; Revised 21 May 2007; Accepted 24 May 2007