Dirk Görlich and Steven McKnight have been awarded the prestigious Albert Lasker Award for Basic Medical Research for their groundbreaking work in understanding the principles of cellular logistics and organization. The Lasker Foundation recognized their discoveries related to low complexity regions (LCRs) of protein sequences, which have significant implications for intracellular transport, pathogenesis, and overall cellular function.
The announcement made by the Lasker Foundation highlights the importance of their findings, which have exposed the structures and functions of these intrinsic regions within proteins. The award, which carries a monetary prize of $250,000, is one of the highest honors in biomedical research and will be presented in New York City on September 19, 2025.
Understanding the Role of Low Complexity Regions
Proteins are critical to numerous biological processes including muscle movement, catalyzing reactions, and providing defense against pathogens. Typically, proteins must fold into specific three-dimensional structures to function properly. However, approximately 30 percent of human protein sequences remain disordered and do not achieve this defined structure, leading to their classification as low complexity regions (LCRs).
These disordered segments are part of what scientists refer to as the “dark proteome,” comprising protein modules devoid of a stable 3D conformation. When mutated, LCRs can contribute to severe neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and Huntington’s disease. For many years, the specific roles of LCRs in healthy cellular function were poorly understood.
“We have discovered that certain LCRs play a central role in cellular logistics and function as ‘smart’ hubs,” Görlich stated. “Receiving the Lasker Award is a great distinction for our entire team and wonderful recognition of our research.”
Görlich’s research focuses on how cells transport proteins to their intended locations, particularly within the nucleus, while simultaneously ensuring that others remain outside. This process is facilitated by the nuclear pore complex (NPC), an intricate structure that regulates the movement of macromolecules.
The Nuclear Pore Complex and Its Functions
The NPC is embedded in the nuclear envelope and exhibits dual functionality. While it is largely impermeable to most macromolecules, it utilizes specialized transporters known as importins and exportins to ferry proteins in and out of the nucleus efficiently. Remarkably, these transport processes can occur at an astonishing rate of up to 1,000 shuttling events per pore per second.
Görlich and his team have played a pivotal role in identifying and characterizing these transporters. They discovered that certain nuclear pore proteins utilize disordered LCRs, known as FG domains, which condense into a gel-like phase. This phase serves as a dynamic barrier that selectively allows transporters and their cargo to traverse while repelling unwanted macromolecules.
The FG phase represents the first instance of a biomolecular condensate arising from disordered protein regions. Such condensates are crucial for regulating biochemical reactions and enabling cellular responses to stress. Initially met with skepticism, Görlich’s findings are now recognized as uncovering fundamental principles of cellular organization.
“Today we know that Dirk Görlich discovered a general principle in living cells,” said Melina Schuh, Managing Director of the Max Planck Institute for Multidisciplinary Sciences. “With the discovery of the FG phase, Dirk has shed light on the dark proteome and opened up a whole new area of research.”
The implications of this research extend beyond basic science. The nuclear pore complex, while essential for normal cellular function, can also be hijacked by pathogens. Recent findings from Görlich’s collaboration with colleagues at the Massachusetts Institute of Technology (MIT) revealed that the HIV virus has adapted its capsid to function as a molecular transporter. This adaptation enables the viral genome to enter the host cell nucleus while evading detection by the cell’s antiviral defenses.
The potential applications of this research are significant. Insights gained from the mechanisms of the HIV capsid could inform the development of improved therapies for AIDS.
Dirk Görlich pursued his studies in biochemistry at the University of Halle and completed his doctoral thesis at the Max Delbrück Center for Molecular Medicine in Berlin. After a two-year research stint at the Wellcome/CRC Institute in Cambridge, he became a research group leader in 1996 and was appointed Professor of Molecular Biology at Heidelberg University in 2001. Since 2007, he has led the Department of Cellular Logistics at the Max Planck Institute for Multidisciplinary Sciences.
His accolades include numerous prestigious awards, such as the Heinz Maier-Leibnitz Prize and the EMBO Gold Medal. Görlich is also a member of the European Molecular Biology Organization (EMBO) and the German National Academy of Sciences Leopoldina.
Founded in 1942 by Albert and Mary Woodard Lasker, the Lasker Foundation aims to promote medical research and recognition of significant contributions in the field. Over the years, the Lasker Awards have been awarded to numerous laureates who later received the Nobel Prize, further underscoring the award’s significance in the biomedical community.
