Since signaling responses differ between different organisms and also within different cell types (primary and cultured), all gathered data will be labeled with great detail according to their origin and environment. the diverse data and perspectives of the research community into a single multidimensional map holds great promise for improved drug design and therapeutic targeting. and the broadly more general (discussed more below) open significant possibilities for creating more effective drugs that have desired therapeutic effects while avoiding deleterious side-effects. Indeed, examples of such biased GPCR ligands for improved treatment of various diseases have already been identified and tested in clinical trials.9 The potential of signaling pathway-specific drugs to improve human health worldwide cannot be understated. Despite this fact, as a field we still know very little about the mechanisms governing ligand bias and functional selectivity. To explain these phenomena, multiple approaches that encompass a wider perspective including information on and signaling events take placewhile taking into account the unique environment inside to GPCR biology, a workshop on GPCR Research Valorization in Amsterdam (2015), and contributions of GLISTEN researchers at the Biophysics Training School in Croatia in 2016.18 The eventual composition of the network (more than 200 research groups from 31 countries) fulfilled the main purpose of GLISTEN to connect researchers and thereby enable cross-disciplinary cooperation. In addition, information exchange was promoted by cross-border exchanges of investigators between laboratories and training colleges that connected experts and novices. The strategies employed by GLISTEN in its activities were highly successful at fostering collaborative research, in particular between experimental and theoretical groups, and ultimately provided useful examples for comparable consortia. Many leading experts of the GPCR field in Europe and worldwide, as well as the key pharmaceutical companies, were regular participants at GLISTEN events. One significant indicator of the importance of GLISTEN to the research community was the popularity of the semiannual meetings. Meetings were often oversubscribed within hours of the opening of online registration, most notably for the meeting in Erlangen that featured Nobel laureate Brian Kobilka as keynote speaker. GLISTEN formally came to an end in 2017, yet its many successes are still being realized. First, more than 65 joint publications stemming from collaborations established within the network have been released. Notable GLISTEN publications are cited here.19?24 In addition, a multitude of joint grants for research funding was acquired by network members, many of which will continue to produce significant scientific findings in the coming years (e.g., Oncornet 2.025 and PSYBIAS26,27). Technology and know-how were spread by GLISTEN-sponsored exchanges of investigators between research groups in different countries and training schools, and the impact of this dissemination will continue to benefit diverse groups and individuals for a long time to come. Relatedly, GLISTEN positively influenced the careers of many early career investigators, which will serve to strengthen the future scientific BMPS output of the field. Last but certainly not least, GLISTEN pushed the development and use of GPCR-focused web-based databases and tools for the benefit of the international research community. GPCRdb, which was originally headed by Gert Vriend at the EMBL in Heidelberg, Germany,28 relocated to the group of David Gloriam at the University of Copenhagen, Denmark in 2013. Several investigator-exchanges and the contributions of GLISTEN members helped this database to grow to contain GPCR reference data, visualization/analysis suites, and tools to design new experiments.1,21,29?31?33 GLISTEN also spurred the creation of GPCRmd, an online repository and visualization platform for molecular dynamics (MD) simulation data and their analysis. This database arose from the need to organize and standardize this information including experimental setups/protocols and to provide intuitive analysis tools. By these means, GPCRmd promotes transparency, consistency, and reproducibility in the field of GPCR dynamics and also facilitates data exchange between GPCR scientists from different disciplines.24 Well before the official end of COST funding, the inclusiveness and influence of GLISTEN drove an intense community-wide desire to evolve a new COST Action. At the same time, developments in the field made clear that in order to meet current challenges, a wider perspective must be taken (explained in detail below). Hence, ERNEST came into.On behalf of ERNEST, M.E.S. ideas of how complexity and specificity in signal transduction are not determined by receptorCligand interactions alone. A holistic approach that unites the diverse data and perspectives of the research community into a single multidimensional map holds great promise for improved drug design and therapeutic targeting. and the broadly more general (discussed more below) open significant possibilities for creating more effective drugs that have desired therapeutic effects while avoiding deleterious side-effects. Indeed, examples of such biased GPCR ligands for improved treatment of various diseases have already been identified and tested in clinical trials.9 The potential of signaling pathway-specific drugs to improve human health worldwide cannot be understated. Despite this fact, as a field we still know very little about the mechanisms governing ligand bias and functional selectivity. To explain these phenomena, multiple approaches that encompass a wider perspective including information on and signaling events take placewhile taking into account the unique environment inside to GPCR biology, a workshop on GPCR Research Valorization in Amsterdam (2015), and contributions of GLISTEN researchers at the Biophysics Training School in Croatia in 2016.18 The eventual composition of the network (more than 200 research groups from 31 countries) fulfilled the main purpose of GLISTEN to connect researchers and thereby enable cross-disciplinary cooperation. BMPS In addition, information exchange was promoted by cross-border exchanges of investigators between laboratories and training schools that connected experts and novices. The strategies employed by GLISTEN in its activities were highly successful at fostering collaborative research, in particular between experimental and theoretical groups, and ultimately provided valuable examples for similar consortia. Many leading experts of the GPCR field in Europe and worldwide, as well as the key pharmaceutical companies, were regular participants at GLISTEN events. One significant indicator of the importance of GLISTEN to the research community was the popularity of the semiannual meetings. Meetings were often oversubscribed within hours of the opening of online registration, most notably for the meeting in Erlangen that featured Nobel laureate Brian Kobilka as keynote speaker. GLISTEN formally came to an end in 2017, yet its many successes are still being realized. First, more than 65 joint publications stemming from collaborations established within the network have been released. Notable GLISTEN publications are cited here.19?24 In addition, a multitude of joint grants for GU2 research funding was acquired by network members, many of which will continue to produce significant scientific findings in the coming years (e.g., Oncornet 2.025 and BMPS PSYBIAS26,27). Technology and know-how were spread by GLISTEN-sponsored exchanges of investigators between research groups in different countries and training schools, and the impact of this dissemination will continue to benefit diverse groups and individuals for a long time to come. Relatedly, GLISTEN positively influenced the careers of many early career investigators, which will serve to strengthen the future scientific output of the field. Last but certainly not least, GLISTEN pushed the development and use of GPCR-focused web-based databases and tools for the benefit of the international research community. GPCRdb, which was originally headed by Gert Vriend at the EMBL in Heidelberg, Germany,28 relocated to the group of David Gloriam at the University of Copenhagen, Denmark in 2013. Several investigator-exchanges and the contributions of GLISTEN members helped this database to grow to contain GPCR reference data, visualization/analysis suites, and tools to design new experiments.1,21,29?31?33 GLISTEN also spurred the creation of GPCRmd, an online repository and visualization platform for molecular dynamics (MD) simulation data and their analysis. This database arose from the need to organize and standardize this information including experimental setups/protocols and to provide intuitive analysis tools. By these means, GPCRmd promotes transparency, consistency, and reproducibility in the field of GPCR dynamics and also facilitates BMPS data exchange between GPCR scientists from different disciplines.24 Well before the official end of COST funding, the inclusiveness and influence of GLISTEN drove an intense community-wide desire to evolve a new COST Action. At the same time, developments in the field made clear that in order to meet current difficulties, a wider perspective must be taken (explained in detail below). Hence, ERNEST came into existence, continuing the excellent tradition of GLISTEN and leading the field in an fascinating new direction. Unresolved Questions in Transmission Transduction To survive and reproduce, all living cells must be able to sense their environments and respond in BMPS an appropriate way. Nature accomplishes this task by transmission transduction, the process of passing external stimuli into and through the cell in order to induce cellular.