mTOR Signaling analysis and proteomic approaches
Proteomic MS technology will allows the analysis of relative quantitative protein abundances and phosphorylation status across different cell lines and conditions. To account for pNET-specific alterations at the expression and phosphorylation level, the proteome and phosphoproteome of pNET cell lines and tumor samples will be analysed under different conditions. Subsequently, protein components that are generally deregulated in pNETs, or which are patient-specific can be derived.
The proteomic data will be further analyzed using a computational pNET-specific model to derive differentially regulated proteins and phospho-proteins with overlapping expression profiles. We will use this approach to reveal in which phase of the MAPK-mTOR signaling network a target is responsive to an input (e.g. therapy). Novel patient- or mutation-specific regulators and effectors will be further analyzed in simulations and experimentally tested. With this approach, the subproject will formulate and parameterize an extended kinetic mTOR model for pENT and use it for simulating therapeutic interferences.
Keywords: Modellparameterisierung, PI3K, mTOR, Signalling