SP5 - SeneSys

Mathematical modeling and specification of relevant oncogenic and senescence-related pathways in DLBCL clusters

Aim of this subproject is to develop computational models in order to analyze molecular perturbations in important signaling and gene regulatory processes of diffuse large B cell lymphoma (DLBCL) in the context of senescence. In recent years, qualitative and quantitative models of critical signaling processes have been successfully developed and prominent perturbations within have been characterized. Based on this work, a representation of a plethora of heterogenous perturbations in previously identified molecular biological DLBCL subtypes can be combined with senescence state to enable the simulation of subtype-specific dynamics and events. In order to integrate the characterized DLBCL subtypes and the senescence state into one representation, modifications and extensions of existing pathway models as well as the inclusion of important crosstalk processes between them are required. We aim to create DLBCL subtype specific models, which characterize critical molecular perturbations in different patient populations. These models are analyzed with regard to find maximal vulnerabilities and to predict target principles for individual DLBCL subtypes. This work will be carried out in close collaboration with experimental, clinical, and bioinformatic subprojects. It is planned to test in-silico predicted functional perturbations in experimental subprojects as well as to simulate experimental and clinical target hypotheses in the computational model.