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Dr Guido Santos - Multi-level computational modeling as a tool to understand molecular mechanisms behind bacterial lung infection
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Descriptif
Pneumonia is oneof the most prevalent infectious diseases worldwide, whose main cause is thepathogen Streptococcus pneumoniae.This is an opportunistic disease affecting the most to sensitive groups(infants, elderly and immunosuppressed people). In these patients theinflammatory response generated in the lungs is the main risk factor thathappens in the very first days of infection. Under this situation the main goalis finding therapeutical or preventive strategies that are able to cut theinflammatory response as soon as possible.
In order toidentify possible molecular targets to focus on this early phase of infectionwe propose a computational approach to simulate the very first stages of thepneumococcal infection happening in a single alveolus. In vivoexperiments at this level are unpracticable with the current technology, whichmakes in silico strategies the best approach. We created a multi-levelmathematical model that combines the intracellular signalling pathways and thecellular interactions that play a role during the early stages of pneumococcalalveolar infection. By systematic perturbations of the model we obtained a highnumber of solutions that we analysed. The results of the analysis of thesimulations predict two main processes that could control the establishment ofthe infection in the alveolus. Bacterial proliferation and bacterial adherencetogether can predict the evolution of the early phases of the pneumococcalinfection.
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