RTG 2816 Non-canonical G protein signaling pathways: Mechanisms, Functions, Consequences
Speaker: Prof. Dr. Dr. Bernd Nürnberg, Co-Speaker: Prof. Dr. Ellen Reisinger
The Research Training Group 2816 (GRK 2816) is an interdisciplinary research consortium with the scientific mission to identify non-canonical G protein-regulated signaling pathways that are clinically and socio-economically important for a number of common diseases such as diabetes mellitus, cancer and stroke, but also for rare diseases. In parallel, an international group of ambitious scientific and medical doctoral students will be guided to doctoral programs through a comprehensive pharmacological and biomedical qualification curriculum embedded in a thematically focused current research program.
The paradigmatic functioning of G-proteins and their regulatory receptors (GPCRs) as well as their downstream signaling cascades form the basis for current pharmacotherapeutic concepts. More than one-third of the drugs in use today act on this signaling pathway either as agonists, inverse agonists, or antagonists, although the GPCR receptor superfamily accounts for only 12% of drug targets. There are more drugs that act on GPCRs than on other proteins or cell structures, including protein kinases or ion channels. Therefore, GPCRs currently serve as exceptional receptors in drug therapy. However, this does not mean that their therapeutic potential has been exhausted. Rather, recent insights into previously largely unknown noncanonical regulatory mechanisms have opened new avenues for promising pharmacotherapeutic interventions in the G protein signaling pathway. The identification of noncanonical signaling pathways regulated by G proteins has greatly expanded the spectrum of G protein-dependent signaling. However, their underlying mechanisms, functions, and biological significance remain largely unexplored.
The main focus of our graduate program aims to fill the gaps in the understanding of selected non-canonical signaling pathways, focusing on ciliopathies, cardiovascular, metabolic, oncological and autophagic diseases. In each project, we focus on processes of functional communication between G-proteins and i) arrestin-GPCR adaptors, ii) activators of G-protein signaling (AGS), iii) nucleoside diphosphate kinases (NDPK, NME), and iv) regulators of G-protein signaling (RGS). These interactions are of great importance for the above diseases, and therefore this interdisciplinary research is intended for young scientists to develop promising new therapeutic strategies.
