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The Lasker Foundation honors Dirk Görlich, director at the Max Planck Institute (MPI) for Multidisciplinary Sciences (Germany), and Steven McKnight, professor at UT Southwestern Medical Center (US), for “discoveries that exposed the structures and functions of protein sequences of low complexity, revealing new principles of intracellular transport, pathogenesis, and cellular organization”, the foundation announced. The prize is widely regarded as America’s preeminent biomedical research award and is endowed with 250,000 US dollars. It will be presented in New York City on Friday, September 19, 2025.
Proteins move our muscles, catalyze biochemical reactions as enzymes, and protect us against pathogens. To perform these tasks, typical proteins must first fold into a defined three-dimensional structure. About 30 percent of human protein sequences, however, never fold and remain intrinsically disordered. They also contain fewer letters of the amino acid alphabet. Accordingly, they are termed low complexity regions (LCRs). Disordered LCRs are part of the “dark proteome” which refers to protein modules that lack a defined 3D structure. If mutated, LCRs can contribute to serious neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Huntington's. For a long time, it was unclear how and why LCRs are used by healthy cells.
Molecular “smart” hubs
“We have discovered that certain LCRs play a central role in cellular logistics and function as ‘smart’ hubs. This has also deciphered important functional principles of the previously poorly understood dark proteome,” Görlich explains. “Receiving the Lasker Award is a great distinction for our entire team and wonderful recognition of our research”.
Görlich studies how cells solve the logistical challenge of transporting their proteins to the right place. This includes importing thousands of different proteins into the cell nucleus, but also keeping many others outside. This sorting is accomplished by one of nature’s most efficient protein transport machines, called the nuclear pore complex (NPC).
NPCs are embedded into the envelope of the nucleus and feature a mysterious functional duality: They are rather impermeable to most macromolecules. However, certain “transporters”, called importins and exportins, are literally sucked into the central NPC channel and released on the other side. This can occur very rapidly – with up to a thousand shuttling events per pore per second. Görlich’s team was instrumental in discovering and analyzing these transporters. They capture macromolecular cargo and either deliver it into the nucleus or export it from there.
“Intelligent” barrier
For their high-performance transport function, nuclear pore complexes rely on a special material: Görlich and his team discovered that the disordered LCR of certain nuclear pore proteins, called FG domains, condense to form a jelly. The driving forces for this condensation are the same that fold enzymes into their functional form; here, they just act between disordered protein segments. This jelly is also known as the FG phase. It functions as an “intelligent” barrier that sorts macromolecules.
The FG phase is repelling for unwanted macromolecules. For molecular transporters, however, it is a good solvent and transport medium. The transporters can pass, along with captured cargo, smoothly through the jelly. The intrinsic disorder of the FG domains allows the barrier to adapt to the various shapes and sizes of cargo-laden transporters, to seal around them and thus to remain a barrier even under high transport load. Thus, Görlich's team demonstrated that molecular transporters, the FG phase and further components together form a highly efficient “pump” for macromolecules.
New field of research opened up
The FG phase was the first example of a biomolecular condensate that originates from disordered protein regions. Many of such condensates are known today. They function inside cells to coordinate biochemical reactions or to help cells to cope with stress. As is often the case in research, Görlich’s discovery was initially met with skepticism as a too exotic form of biological matter.
“Today we know that Dirk Görlich discovered a general principle in living cells”, says Melina Schuh, Managing Director of the MPI for Multidisciplinary Sciences. “Cellular condensates in the cell form new, highly dynamic compartments that perform important functions. With the discovery of the FG phase, Dirk Görlich has shed light on the dark proteome and opened up a whole new area of research. We are therefore thrilled that his groundbreaking research work is being honored with the Lasker Award and congratulate him on this prestigious prize.”
HIV: Smuggling genetic material into the cell nucleus
The “smart hub” nuclear pore complex is of fundamental importance for organisms ranging from yeast to humans. However, it can also be exploited by pathogens. A particularly sophisticated strategy was recently reported Görlich’s team in collaboration with MIT colleagues. They discovered that the AIDS virus HIV has evolved its capsid into a molecular transporter that smuggles the viral genome into the nucleus of the host cell. The capsid not only encloses the viral genome, but can also directly cross the FG phase, which is a central line of defense to protect the cell nucleus against invading viruses. During this smuggling process, the HIV genome remains virtually invisible to the antiviral sensors in the cytoplasm. This finding could be used in the future to develop better AIDS therapies.
About the awardee
Dirk Görlich studied biochemistry in Halle and completed his doctoral thesis at the Max Delbrück Center for Molecular Medicine in Berlin. After a two-year research stay at the Wellcome / CRC Institute (now: Gurdon Institute) in Cambridge (United Kingdom), he was appointed research group leader in 1996 and Professor of Molecular Biology at the Center for Molecular Biology at Heidelberg University in 2001. Since 2007, he has headed the Department of Cellular Logistics at the MPI for Multidisciplinary Sciences (until 31.12.2021: MPI for Biophysical Chemistry). Dirk Görlich has received numerous scientific awards, including the Heinz Maier-Leibnitz Prize, the EMBO Gold Medal, the Alfried Krupp Prize, the WLA Prize 2022, the Louis Jeantet Prize 2024, and the Animal Welfare Research Prize of the Federal Ministry of Food and Agriculture. He is a member of the European Molecular Biology Organization (EMBO) and the German National Academy of Sciences Leopoldina.
About the Lasker Foundation and the Albert Lasker Award
In 1942, Albert and Mary Woodard Lasker founded the New York-based Lasker Foundation to encourage financial support for medical research. The Lasker Awards recognize the contributions of leaders who have made major advances in the understanding, diagnosis, treatment, cure, and prevention of human disease. Each prize is endowed with 250.000 US dollars
The award is considered the highest biomedical research prize in the US. Over the years, 101 Lasker Laureates have also received the Nobel Prize, including three Max Planck researchers: Georges Köhler, Christiane Nüsslein-Vollhard, and Ernst Ruska.
Prof. Dr. Dirk Görlich
Department of Cellular Logistics
Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
Phone: +49 551 201-2400
Email: goerlich@mpinat.mpg.de
https://www.mpinat.mpg.de/5111108/pr_2517 – Original press release
https://laskerfoundation.org/ – Website of the Lasker Foundation
https://www.mpinat.mpg.de/goerlich – Website of the Department of Cellular Logistics, Max Planck Institute for Multidisciplinary Sciences
Prof. Dr. Dirk Görlich
Quelle: Irene Böttcher-Gajewski
Copyright: Max Planck Institute for Multidisciplinary Sciences
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Prof. Dr. Dirk Görlich
Quelle: Irene Böttcher-Gajewski
Copyright: Max Planck Institute for Multidisciplinary Sciences
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