Dirk GÖRLICH, of German nationality, is awarded the 2024 Louis-Jeantet Prize for Medicine for elucidating how the directionality of cargo transfer between the cytoplasm and nucleus is achieved and for his discovery of the selective FG phase that governs transport through nuclear pores.
Born in 1966, Dirk Görlich studied biochemistry at the University of Halle and did his doctoral studies with Tom A. Rapoport at the Max Delbrück Center in Berlin. After a two-year postdoctoral stay in the laboratory of Ron Laskey in Cambridge (UK), he joined the ZMBH (University of Heidelberg) where he became an independent group leader in 1996 and Professor of Molecular Biology in 2001. Since 2005, he has been Scientific Member and Director at the Max Planck Institute for Biophysical Chemistry in Göttingen, now the Max Planck Institute for Multidisciplinary Sciences.
Dirk Görlich was elected as a member of the European Molecular Biology Organization (EMBO) in 1997 and of the German National Academy of Sciences Leopoldina in 2005. He received the EMBO Gold Medal in 1997 and the WLA Prize in 2022.
An FG phase governing transport selectivity of nuclear pores
Cell nuclei cannot synthesise proteins and must import all the proteins they need from the cytoplasm. At the same time, they supply the cytoplasmic compartment with tRNA, mRNA, and assembled ribosomes. This nucleocytoplasmic transport proceeds through nuclear pore complexes (NPCs) and plays a fundamental role in eukaryotic cells. Dirk Görlich has made textbook contributions to this field: he discovered the first importins that shuttle between the two compartments, capturing cargoes in the cytoplasm and delivering them into the nucleus; he was instrumental in the discovery and characterisation of exportins; and he developed the RanGTP gradient model to explain the directionality and energetics of nuclear transport.
In transformative work that started in 2001, Görlich showed that the NPC is a quite special transport machine – equipped with a selective barrier that decides which molecules move in and out of the nucleus. It features a mysterious functional duality: for most particles it appears impenetrable. Importins, exportins, and related shuttling transporters, however, are sucked into NPCs and released on the other side. This can happen at a very high rate – up to a thousand times per pore per second. To function as a highly efficient transport machine, NPCs rely on so-called ‘FG repeats’ that are anchored to the pore. Görlich and his team discovered that these intrinsically disordered FG repeats can engage in cohesive interactions and thereby condense into an ‘FG phase’ that functions as a permeability barrier with extreme transport selectivity and capacity. The FG phase can be considered a good ‘solvent’ and transport medium for importins and exportins, together with their captured cargo. At the same time, it repels macromolecules that are not recognised as valid cargoes. The FG phase discovered by Görlich was the first and remains a fundamentally relevant example of a biomolecular condensate originating from intrinsically disordered protein domains. It can be seen as the starting point of a new field with broad implications throughout biology and medicine.