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The molecular network of “death receptors” on trial

The international ApoNET research project, which is part of a European-wide systems biology initiative, is coordinated by the Mannheim Medical Faculty at the University of Heidelberg. ApoNET researchers use modern genome sequencing methods and computer models to gain a better understanding of apoptosis networks in liver cells. The project is funded by the German Federal Ministry of Education and Research and the European Union with 1.7 million euros under the ERASysBio+ programme.

Professor Dr. Michael Boutros, head of the Department of Cell and Molecular Biology at the Mannheim Medical Faculty of the University of Heidelberg and head of the Department of Signalling and Functional Genomics at the German Cancer Research Centre, is the coordinator of the interdisciplinary EU consortium ApoNET. The project partners are Professor Dr. Rainer Spang (University of Regensburg) and Professor Dr. Henning Walczak (Imperial College London, UK).

Innovative cancer therapies focus on inducing the death of cancer cells without destroying healthy cells. However, some types of cancer are resistant to such types of therapy because the cancer cells are unable to initiate programmed cell death (apoptosis). Apoptosis refers to the death of cells mediated by a highly regulated intracellular programme. Death receptors have been shown to play a key role in this process.

Fluorescence-stained liver cancer cells [blue: nuclei; green: cytoskeleton (actin), red: cytoskeleton at the connections between cells (phalloidin staining)] © Universitätsmedizin Mannheim UMM

Hepatocellular carcinoma is a common type of cancer worldwide. The treatment of this disease often fails due to defective apoptosis signalling. In order to be able to develop effective therapies for the treatment of hepatocellular carcinoma, it is important to understand how the apoptosis signalling networks are regulated in normal liver cells and deregulated in cancer cells.

The goal of the ERASysBio+ consortium led by Professor Boutros is to systematically analyse the function of death receptor signalling networks in hepatocellular carcinoma. The interdisciplinary research of the consortium is closely linked to research being carried out by the project partners Professor Spang and Professor Walczak. The goal of the transnational project is to understand the basic biological system that governs the signals in normal and defective liver cells in order to be able to make predictions relating to the system. Based on experimental high-throughput sequencing data compiled by Professor Boutros' and Professor Walczak's research groups, Professor Spang's group of researchers will generate computer-based models in order to identify the critical steps in the regulation of these signalling pathways. The statistic models will be used by the scientists to reconstruct the activities of the signalling pathways in liver cells and to find potential new targets for therapies.

In addition to the new findings in the transmission of signals via death receptors in normal and altered cells on the systems level, the scientists expect that the study will also lead to new insights into the principal mechanisms of tumour development and the therapy of resistant tumours.

ERA-NET ERASysBio+

ERA-Net ERASysBio+ is a programme that specifically promotes the application of systems biology research in the area of biomedicine in EU partner states. Its goal is to establish transnational research and development projects in the field of the fast developing interdisciplinary science of systems biology.

ERA stands for "European Research Area" and hence for the coordination of research and technological development activities in Europe and on the national level.

Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/the-molecular-network-of-death-receptors-on-trial