GRK 2816:  Non-canonical G protein signaling pathways: Mechanisms, functions, consequences

• Subject Area: Medicine
• Term: since 2022
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 464254052

The classical G protein-dependent signaling paradigm defines the interaction of three key players: the activated G protein-coupled receptor (GPCR), the transducing heterotrimeric G protein and its intracellular effector. The emerging identification of several non-canonical G protein signaling pathways has broadened the spectrum of G protein-dependent processes and promises exciting new avenues for the development of rational pharmacological interventions. Non-canonical G protein-dependent signaling pathways control critical biological processes that are crucial for severe human diseases, some of which are major health burdens like diabetes mellitus, cancer and stroke. However, underlying mechanisms, functions and biological implications are not adequately explored. Hence, our RTG initiative aims to fill the gaps in understanding selected non-canonical signaling pathways and to translate the gained knowledge into pharmaco-therapeutic ideas for tailored medicine. The planned RTG projects will concentrate on important non-canonical G protein-dependent processes that are highly relevant to serious human diseases: Functional communication between G proteins and i) GPCR-interacting arrestin adaptors, ii) the activators of G protein signaling proteins GIV/ Girdin, Daple, GPSM1/ 2, iii) nucleoside diphosphate kinases, and iv) the G protein regulator RGS4. This focus offers talented young researchers appealing up-to-date research topics and cutting-edge technology to uncover non-canonical G protein signaling mechanisms in particular cardiovascular, metabolic, autophagic and tumor diseases, as well as in ciliopathies. Our RTG initiative will promote interdisciplinary research to explore its basic mechanisms, biological roles and translational potential. Our students will receive a comprehensive and profound pharmacological training in drug screening, pharmacodynamics, -kinetics, and -genetics as well as molecular and clinical pharmacology. Our PIs that are perfectly integrated in Tübingen’s priority research areas enable the RTG to bring together unique resources and a state-of-the-art infrastructure that are provided under the umbrella of Tübingen’s core research consortia, such as the Clusters of Excellence, German Centers for Health Research, and Collaborative Research Centers among others. In parallel, a structured educational qualification program will take place that interconnects with the qualification curricula of the Medical Faculty and Tübingen’s Graduate Academy with its soft skills and supporting programs. Hence, our interdisciplinary pharmacology-orientated research and education concept will qualify next-generation life science and medical trainees on an internationally competitive level in order to meet the urgent local and nation-wide demand for highly qualified young researchers trained in pharmacology.

• DFG Programme: Research Training Groups
• Applicant Institution: Eberhard Karls Universität Tübingen
• Spokesperson: Professor Dr. Bernd Nürnberg
• Participating Researchers: Professorin Dr. Sandra Beer-Hammer; Professor Dr. Andreas L. Birkenfeld; Madhumita Chatterjee, Ph.D.; Professor Dr. Robert Feil; Privatdozent Dr. Timo Müller; Professorin Dr. Tassula Proikas-Cezanne; Professorin Dr. Ellen Reisinger; Professorin Dr. Birgit Schittek; Professor Dr. Matthias Schwab; Dr. Elke Schäffeler; Professorin Dr. Bettina Weigelin; Professor Thomas Wieland, Ph.D.