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[1] J. Smith, R. Lefkowitz, S. Rajagopal, Nat. Rev. Drug. Discov., 17, 243-260 (2018)
\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
This paper studies optimal financial flexibility in debt issuance. A borrower raises funds for an initial investment and may need financing after observing a private liquidity shock. Under non exclusive lending, new lenders price only their claims, so additional borrowing dilutes existing debt and leads to excessive leverage. The optimal simple debt contract is an endogenous debt limit. It captures the intertemporal commitment–flexibility tradeoff: more borrowing today fi nances investment but increases dilution incentives, requiring tighter limits on future borrowing. Richer clauses, including performance-sensitive debt and contingent prepayment provisions, re store the exclusive-lending benchmark by compensating existing lenders when new financing is raised.
","image_description":"","creation_date":"2026-06-03T15:01:15","last_modification_date":"2026-09-30T13:50:47","link_label":"Paper","link_url":"https://yunzhihu.web.unc.edu/wp-content/uploads/sites/14825/2026/08/draft-v4.pdf","canceled":"False","cancel_reason":"","place_and_room":"UNIL, Extranef, room 126","url_place_and_room":"","url_online_room":"","spoken_languages":["https://memento.epfl.ch/api/v1/spoken_languages/2/?format=json"],"speaker":"Yunzhi Hu - The University of North Carolina","organizer":"","contact":"sophie.cadenakauz@epfl.ch","is_internal":"False","theme":"","vulgarization":{"id":2,"fr_label":"Public averti","en_label":"Informed public"},"registration":{"id":3,"fr_label":"Entrée libre","en_label":"Free"},"keywords":"","file":null,"icalendar_url":"https://memento.epfl.ch/event/export/120962/","category":{"id":1,"code":"CONF","fr_label":"Conférences - Séminaires","en_label":"Conferences - Seminars","activated":true},"academic_calendar_category":null,"domains":[],"mementos":["https://memento.epfl.ch/api/v1/mementos/112/?format=json","https://memento.epfl.ch/api/v1/mementos/3/?format=json","https://memento.epfl.ch/api/v1/mementos/116/?format=json","https://memento.epfl.ch/api/v1/mementos/105/?format=json"]},{"id":72194,"title":"Neuro-X seminar: Prof Tim O'Shea - Engineering astrocytes to promote wound repair and modulate foreign body responses in the CNS","slug":"neuro-x-seminar-prof-tim-o-shea-engineering-astroc","event_url":"https://memento.epfl.ch/event/neuro-x-seminar-prof-tim-o-shea-engineering-astroc","visual_url":"https://memento.epfl.ch/image/33474/200x112.jpg","visual_large_url":"https://memento.epfl.ch/image/33474/720x405.jpg","visual_maxsize_url":"https://memento.epfl.ch/image/33474/max-size.jpg","lang":"en","start_date":"2026-10-09","end_date":"2026-10-09","start_time":"11:00:00","end_time":"12:00:00","description":"Astrocytes are the predominant glial cells in the mammalian central nervous system (CNS) and play essential roles in maintaining neural circuit activity and tissue homeostasis. In response to CNS insult, including traumatic injury or implantation of a medical device, astrocytes undergo a conserved, temporally regulated reprogramming that reshapes their prioritized functions to protect adjacent neural tissue. The nature and extent of astrocyte reprogramming critically influences outcomes after CNS insult. For example, regeneration after traumatic CNS injury in adult mammals is limited by local responding astrocytes lacking sufficient self-renewal capacity. By contrast, the CNS of neonate (newborn) mammals possesses exceptional parenchymal repair capacity owing to immature astrocytes with elevated proliferative and migratory potential. In the context of an implanted medical device, the spatial extent of astrocyte reprogramming and how impacted astrocytes respond to any further device micromotion, latent infection, or other persistent device-derived stimuli, dictates device performance and longevity. Engineering astrocyte responses to promote targeted functional gains while preserving key capabilities of healthy neural tissue astrocytes will be critical to enabling effective neural regeneration therapies and improving long-term performance of implanted devices. In this talk, I will outline our emerging understanding of how adult astrocytes adaptively reprogram in response to CNS injury and implanted foreign bodies, drawing insights from innovative astrocyte-specific transcriptomic bioassays. I will also provide an overview of biomaterial and cell-grafting strategies that we are exploring to direct astrocyte responses in preclinical models of stroke, spinal cord injury, and foreign body responses.
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\r\nBio:
\r\nDr. Timothy O’Shea, PhD is an Assistant Professor in the Biomedical Engineering department at Boston University (BU). Tim grew up in Brisbane, Australia and completed a Bachelor of Medical Engineering (First Class Honours) and a Masters in Engineering Management at Queensland University of Technology (QUT) before moving to the US for graduate school. He completed his PhD study in Medical Engineering and Medical Physics within the collaborative Health Sciences and Technology program of the Harvard Medical School and the Massachusetts Institute of Technology where we conducted PhD thesis research with Institute Professor Robert Langer. As a Postdoctoral Fellow in Neurobiology at UCLA, he worked with Professors Michael Sofroniew (Neurobiology) and Timothy Deming (Bioengineering) developing and testing novel bioengineering tools to study biological mechanisms involved in CNS injury and repair as well as the CNS foreign body response to implants. Since Fall 2020 he has been leading the Glia Engineering Lab at BU where he has received numerous awards including the Maximizing Investigators' Research Award (MIRA) from NIH and grants from several spinal cord injury research foundations such as Craig H Neilsen, Paralyzed Veterans of America, Bryon Reisch, and Wings for Life.
In 2026, EPFL named Professor Konstantin Novoselov its first-ever EPFL Fellow, a newly created honorary title recognising scientific personalities of exceptional international stature.
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\r\nEPFL is delighted to host a public lecture to celebrate this nomination of one of the most influential physicists of our time.
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\r\nKonstantin Novoselov was awarded the Nobel Prize in Physics in 2010 and is globally renowned for his pioneering work on graphene and two-dimensional materials. By isolating graphene for the first time, a sheet of carbon just one atom thick, he opened an entirely new field of research, with profound implications for electronics, energy and quantum technologies.
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\r\nPicture this: it was from the graphite of an ordinary pencil lead that this \"super-material\" was first isolated. Using nothing more than a piece of adhesive tape to peel away a layer a single atom thick, Konstantin Novoselov revealed to the world a material with extraordinary properties. A million times thinner than a human hair, 200 times stronger than steel and remarkably conductive, graphene pushes every limit. From the lead of your pencil to the batteries of tomorrow, join us to discover how a deceptively simple gesture set off a genuine technological revolution.
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\r\nThis Campus Lecture offers an introduction to that revolution: how a two-dimensional material is transforming our understanding of matter and how today's fundamental discoveries become tomorrow's technologies.
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\r\nAbout Konstantin Novoselov
\r\nKonstantin Novoselov is a physicist specialising in condensed matter and nanotechnology. He conducted his Nobel Prize–winning research at the University of Manchester, where, together with Professor Andre Geim, he isolated graphene for the first time. He has held academic positions in the United Kingdom as well as internationally and is currently based at the National University of Singapore. Widely recognised as a leading figure in the study and application of two-dimensional materials, he has received numerous honours for his contributions to science.
Thesis Director: Prof. N. Marzari,
\r\nMaterials Science and Engineering doctoral program
\r\nThesis Nr. 11813
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\r\nTo take part in the public defense, please contact directly the speaker
Thesis Director: Prof. J. McKinney,
\r\nBiotechnology and Bioengineering doctoral program
\r\nThesis Nr. 11625
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\r\nTo take part in the public defense, please contact directly the speaker
Thesis Directors: Prof. S. Süsstrunk, Dr R. Achanta
\r\nComputer and Communication Sciences doctoral program
\r\nThesis Nr. 11581
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\r\nTo take part in the public defense, please contact directly the speaker