NR AWIZ
AU Lenuzza,N.; Aubry,F.; Picoli,C.; Nouvel,V.; Charveriat,M.; Correia,E.; Reboul,M.; Fouliard,S.; Benhamida,S.; Laurent,P.; Saguez,C.; Deslys,J.P.; Mouthon,F.
TI Prion intercellular propagation: at the frontier of mathematical and biological approaches
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-23
PT Konferenz-Poster
AB The mechanisms involved in the misfolding of PrPsc, in its accumulation and in its intercellular propagation remain poorly understood. Moreover, the study of these phenomena at a single cell scale is difficult with the existing in vitro and in vivo approaches. At this level, complementary approaches can benefit from cellular automata mathematical theory which allows to investigate in what way a local parameter, related to a particular cell, can influence the global behavior of a system. Thus, we programmed a cellular automata to mimick prion propagation in a cell culture. Our model allows us to set every wanted single cell-related parameter, as cell-cycle length, death rate, Prnp gene expression, level of infectivity. Depending on these parameters, some rules simulating the cellular metabolism of PrPc and PrPres (production, degradation, misfolding) have been implemented. These rules are based on the existing intracellular models of prion proliferation. They simulate prion propagation at a unicellular level. In addition, some rules concerning prion propagation from one cell to another one (by cell contact or by secretion of PrPsc in culture medium) have been added. To estimate experimentally the different parameters included in our model, we used two cell lines, GT1-7 and SN56, chronically infected by Chandler prion strain. A magnetic cell sorting of infected cell lines, based on membrane expression of PrP, has been realized, that enriched the different cell line in infected cells. Thus, slight differences in PrP expression and in cell growth between infected and uninfected cells have been highlighted whereas no difference was observable before sorting. The different experimental observations are included regularly in the mathematical model to implement the parameters to be studied. The influence of each hypothetic local rule (limited to one cell and its nearest neighboorhood) on the global behavior of the in silico culture is evaluated. The comparison with experimental data will allow to select the most realistic rules, and therefore investigate more precisely the cellular mechanisms potentially involved. Even if the model is still far from a real culture, such a multidisciplinar approach constitutes a new original perspective in the comprehension of prion infection.
AD N. Lenuzza: CEA/DSV/DRM/GIDTIP, Fontenay-aux-Roses, France, and Laboratoire MAS, Ecole Centrale Paris, Chatenay-Malabry, France; F. Aubry, C. Picoli, V. Nouvel, M. Charveriat, E. Correia, M. Reboul, J.-P. Deslys, F. Mouthon: CEA/DSV/DRM/GIDTIP, Fontenay-aux-Roses, France; S. Fouliard, S. Benhamida, P. Laurent, C. Saguez: Laboratoire MAS, Ecole Centrale Paris, Chatenay-Malabry, France. E-mail: natacha.lenuzza@cea.fr
SP englisch
PO Italien