Cytokineproteomics · Investigating inflammatory signaling by combining phospho- and ubiquitin proteomics with CRISPR/Cas9 technology

Investigating inflammatory signaling by combining phospho- and ubiquitin proteomics with CRISPR/Cas9 technology

Cytokines are implicated in many disease settings. Successful therapeutic targeting of cytokine signalling is challenging: whereas targeting one cytokine in most inflammatory diseases is not sufficient to prevent inflammation, this can already be enough to induce many side effects due to multifunctional roles of cytokines. There is an urgent need to better understand the regulation of cytokine signaling to design more efficient anti-inflammatory therapies. This can only be achieved by investigating the signalling interplay of multiple cytokines, which has been poorly studied due to its complexity. Signal transduction of cytokine signalling pathways occur through posttranslational modifications (PTMs) of signalling components. To investigate signaling crosstalk it is important to capture and analyse those PTMs in an unbiased, system-based manner. Mass spectrometry-based proteomics has matured remarkably in the last years and now provides a comprehensive discovery tool to address diverse biological questions. To analyse signaling events we enrich for posttranslational modification, which are subsequently analysed in a highly quantitative fashion. Thereby we aim to identify crucial signaling events for cytokine signaling in isolation and in context of other cytokines. These findings will give more insights into cytokine signaling and might provide more suitable drug targets. Targeting downstream signaling events instead of inhibiting cytokine pathways upstream (e.g. TNF inhibition) could be a potential approach to reduce treatment toxicity.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз