Conflicts are part of daily life and commonly arise in a business environment. Poorly managed, or not properly resolved, they can cause significant harm, both on an interpersonal level and for the organisation itself. Productivity may be affected and finances impacted as a result of tensions between colleagues.
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\r\nDifferent approaches to conflict management are increasingly being used, helping clarify messy situations, lessening the tensions and enabling employees to continue to work together.
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\r\nThis seminar presents several separate yet related methods of conflict management. One of which, mediation, enables the parties in dispute to work towards a viable solution by taking into account all the different aspects of the problem. The mediator, as a neutral third party, uses tools and communication skills to help the parties elaborate, themselves, mutually satisfactory solutions. Participants will learn skills that will enable them to understand conflict and to manage, and ultimately resolve, disputes.
Prendre sa retraite après un long parcours professionnel ne va pas forcément de soi, si l'on pense à la place prise par le travail dans son parcours de vie. Le séminaire a pour objectif d'aider les participant.e.s à identifier les changement que cette transition introduira dans leur existence, afin d'anticiper et construire un nouvel équilibre de vie. Il s'agit également de conscientiser tous les aspects de cette période de la vie et les adaptations à réaliser, seul.e ou en couple, ainsi qui de définir les axes principaux et futures activités et projets. Les questions liées aux aspects financiers et au maintien de son capital santé, sont aussi abordées.
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\r\nComprendre ces mécanismes, apprendre à les réguler, et surtout identifier ses propres déclencheurs et ressources devient alors essentiel pour évoluer dans un cadre professionnel et promouvoir un travail stable et une qualité de vie plus saine.
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\r\nCette formation vise à renforcer votre résilience, vous permettre d’identifier vos déclencheurs personnels, et d’activer des ressources internes et externes pour retrouver calme, clarté mentale et stabilité au quotidien.
You can apply to participate and find all the relevant information (speakers, abstracts, program,...) on the event website: https://www.cecam.org/workshop-details/g-protein-coupled-receptors-functional-dynamics-revealed-by-experimental-and-computational-structural-data-1488.
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\r\nRegistration is required to attend the full event, take part in the social activities and present a poster at the poster session (if any). However, the EPFL community is welcome to attend specific lectures without registration if the topic is of interest to their research. Do not hesitate to contact the CECAM Event Manager if you have any question.
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\r\nDescription
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\r\nG protein-coupled receptors (GPCRs) represent a vast and diverse class of transmembrane proteins that orchestrate a wide range of physiological processes by responding to both endogenous and exogenous ligands [1,2]. These receptors are essential to critical functions such as metabolism, immune regulation, neuronal signaling, and sensory perception - including vision and olfaction. Due to their physiological relevance and membrane accessibility, GPCRs are the targets of approximately 34% of all prescribed medications, accounting for nearly 27% of the global pharmaceutical market [3].
\r\nDespite their pharmaceutical importance, key aspects of GPCR function remain elusive. The canonical activation model posits that agonist binding to the extracellular orthosteric site triggers allosteric changes - most notably, the outward displacement of transmembrane helices 5 (TM5) and 6 (TM6) on the intracellular side - ultimately leading to receptor activation [2-4]. However, recent evidence suggests a more nuanced mechanism. In several GPCRs, activation appears to involve cooperative engagement between the agonist and the G protein. For example, the G protein may disrupt an \"inactivating ionic lock\" - a salt bridge between TM3 and TM6 - while the agonist stabilizes the active conformation. In some receptors, this is complemented by the formation of an “activating ionic lock” between TM5 and TM6 [5-8]. These dual contributions are considered thermodynamically essential for full activation [7].
\r\nAdding further complexity, GPCR activity is regulated by conformational microswitches and finely tuned intra-protein interaction networks. These dynamic rearrangements are difficult to capture and often elude direct correlation with functional outcomes. Moreover, allosteric ligands - which bind sites distinct from the orthosteric pocket - are being increasingly identified [9-12], along with small molecules capable of biased signaling, i.e., preferential activation of specific intracellular pathways [11-13, 16, 17]. These findings reveal a rich and underexplored conformational landscape that governs GPCR signaling. In addition, native membrane components—such as lipids and interacting proteins, including GPCR oligomers—are known to significantly modulate receptor function [11, 18-22].
\r\nTo disentangle these intricacies, computational modeling has become indispensable, offering atomistic insight into GPCR conformational dynamics and mechanistic understanding [1-2, 7, 11, 14, 16–21, 23]. Nevertheless, key questions remain - particularly regarding the structural basis of biased signaling, strategies for leveraging allosteric networks in pharmacology, and the modulatory role of the lipid environment. Addressing these gaps is crucial for both fundamental biology and the rational design of next-generation GPCR-targeting drugs with improved selectivity and safety profiles.
\r\nThese scientific challenges form the foundation of our upcoming workshop, which will focus on the latest experimental and computational approaches for studying the functional dynamics of GPCRs. Given the profound health, economic, and societal implications of modulating these receptors with precision, we aim to strengthen the interdisciplinary nature of the event by increasing the representation of experimental research and integrating cutting-edge artificial intelligence applications into the program.
\r\nBuilding upon the success of the 2022 and 2024 editions - which led to new collaborations and a landmark publication in Nature Reviews Drug Discovery [24] - our goal is to further enhance communication and collaboration between experimentalists and theoreticians. The workshop will serve as a reference point for young scientists and students, offering a platform to interact with leading international experts. We are confident that this initiative will foster insightful discussions and contribute meaningfully to advancing the field of GPCR pharmacology.
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\r\nReferences
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\r\n[2] P. Conflitti, E. Lyman, M. Sansom, P. Hildebrand, H. Gutiérrez-de-Terán, P. Carloni, T. Ansell, S. Yuan, P. Barth, A. Robinson, C. Tate, D. Gloriam, S. Grzesiek, M. Eddy, S. Prosser, V. Limongelli, Nat. Rev. Drug. Discov., 24, 251-275 (2025)
\r\n[3] L. Picard, A. Orazietti, D. Tran, A. Tucs, S. Hagimoto, Z. Qi, S. Huang, K. Tsuda, A. Kitao, A. Sljoka, R. Prosser, Nat. Chem. Biol., 21, 71-79 (2024)
\r\n[4] B. Huang, C. St. Onge, H. Ma, Y. Zhang, Drug Discovery Today, 26, 189-199 (2021)
\r\n[5] D. Di Marino, P. Conflitti, S. Motta, V. Limongelli, Nat. Commun., 14, 6439 (2023)
\r\n[6] G. Milligan, R. Ward, S. Marsango, Current Opinion in Cell Biology, 57, 40-47 (2019)
\r\n[7] S. Huang, O. Almurad, R. Pejana, Z. Morrison, A. Pandey, L. Picard, M. Nitz, A. Sljoka, R. Prosser, eLife, 11, (2022)
\r\n[8] A. Duncan, W. Song, M. Sansom, Annu. Rev. Pharmacol. Toxicol., 60, 31-50 (2020)
\r\n[9] A. Morales-Pastor, T. Miljuš, M. Dieguez-Eceolaza, T. Stępniewski, V. Ledesma-Martin, F. Heydenreich, T. Flock, B. Plouffe, C. Le Gouill, J. Duchaine, D. Sykes, C. Nicholson, E. Koers, W. Guba, A. Rufer, U. Grether, M. Bouvier, D. Veprintsev, J. Selent, Nat. Commun., 16, 5265 (2025)
\r\n[10] A. Faouzi, H. Wang, S. Zaidi, J. DiBerto, T. Che, Q. Qu, M. Robertson, M. Madasu, A. El Daibani, B. Varga, T. Zhang, C. Ruiz, S. Liu, J. Xu, K. Appourchaux, S. Slocum, S. Eans, M. Cameron, R. Al-Hasani, Y. Pan, B. Roth, J. McLaughlin, G. Skiniotis, V. Katritch, B. Kobilka, S. Majumdar, Nature, 613, 767-774 (2022)
\r\n[11] M. Wall, E. Hill, R. Huckstepp, K. Barkan, G. Deganutti, M. Leuenberger, B. Preti, I. Winfield, S. Carvalho, A. Suchankova, H. Wei, D. Safitri, X. Huang, W. Imlach, C. La Mache, E. Dean, C. Hume, S. Hayward, J. Oliver, F. Zhao, D. Spanswick, C. Reynolds, M. Lochner, G. Ladds, B. Frenguelli, Nat. Commun., 13, 4150 (2022)
\r\n[12] D. Wootten, A. Christopoulos, M. Marti-Solano, M. Babu, P. Sexton, Nat. Rev. Mol. Cell. Biol., 19, 638-653 (2018)
\r\n[13] D. Hilger, M. Masureel, B. Kobilka, Nat. Struct. Mol. Biol., 25, 4-12 (2018)
\r\n[14] D. Aranda-García, T. Stepniewski, M. Torrens-Fontanals, A. García-Recio, M. Lopez-Balastegui, B. Medel-Lacruz, A. Morales-Pastor, A. Peralta-García, M. Dieguez-Eceolaza, D. Sotillo-Nuñez, T. Ding, M. Drabek, C. Jacquemard, J. Jakowiecki, W. Jespers, M. Jiménez-Rosés, V. Jun-Yu-Lim, A. Nicoli, U. Orzel, A. Shahraki, J. Tiemann, V. Ledesma-Martin, F. Nerín-Fonz, S. Suárez-Dou, O. Canal, G. Pándy-Szekeres, J. Mao, D. Gloriam, E. Kellenberger, D. Latek, R. Guixà-González, H. Gutiérrez-de-Terán, I. Tikhonova, P. Hildebrand, M. Filizola, M. Babu, A. Di Pizio, S. Filipek, P. Kolb, A. Cordomi, T. Giorgino, M. Marti-Solano, J. Selent, Nat. Commun., 16, 2020 (2025)
\r\n[15] D. Thal, A. Glukhova, P. Sexton, A. Christopoulos, Nature, 559, 45-53 (2018)
\r\n[16] L. Slosky, M. Caron, L. Barak, Trends in Pharmacological Sciences, 42, 283-299 (2021)
\r\n[17] C. Zhu, X. Lan, Z. Wei, J. Yu, J. Zhang, Acta Pharmaceutica Sinica B, 14, 67-86 (2024)
\r\n[18] V. D’Amore, P. Conflitti, L. Marinelli, V. Limongelli, Chem, 10, 3678-3698 (2024)
\r\n[19] A. Mafi, S. Kim, W. Goddard, Nat. Chem., 15, 1127-1137 (2023)
\r\n[20] H. Batebi, G. Pérez-Hernández, S. Rahman, B. Lan, A. Kamprad, M. Shi, D. Speck, J. Tiemann, R. Guixà-González, F. Reinhardt, P. Stadler, M. Papasergi-Scott, G. Skiniotis, P. Scheerer, B. Kobilka, J. Mathiesen, X. Liu, P. Hildebrand, Nat. Struct. Mol. Biol., 31, 1692-1701 (2024)
\r\n[21] A. Manglik, T. Kim, M. Masureel, C. Altenbach, Z. Yang, D. Hilger, M. Lerch, T. Kobilka, F. Thian, W. Hubbell, R. Prosser, B. Kobilka, Cell, 161, 1101-1111 (2015)
\r\n[22] M. Congreve, C. de Graaf, N. Swain, C. Tate, Cell, 181, 81-91 (2020)
\r\n[23] J. Lorente, A. Sokolov, G. Ferguson, H. Schiöth, A. Hauser, D. Gloriam, Nat. Rev. Drug. Discov., 24, 458-479 (2025)
\r\n[24] M. Lopez‐Balastegui, T. Stepniewski, M. Kogut‐Günthel, A. Di Pizio, M. Rosenkilde, J. Mao, J. Selent, British. J. Pharmacology., 182, 3211-3224 (2024)\r\n