Chromosomes are very long polymers with a dynamic structure that is crucial for their function. Molecular motors, so-called SMC protein complexes, are key to this spatial organization, bridging distantly located regions of DNA. But how do these motors work and how do they regulate gene expression?
Professor Mirny, of MIT’s Institute of Medical Engineering and Science (IMES) and the Department of Physics, along with researchers from Delft Technical University, the University of Edinburgh, and the Netherlands Cancer Institute have been awarded the Synergy grant “GeneMotors” from the European Research Council. The aim of Synergy Grants is to provide support for groups of Principal Investigators to jointly address ambitious research problems that could not be addressed by the individual Principal Investigators alone. Collaborating over 6 years, the Gene Motors project will harness their complementary expertise in theoretical modelling, biophysics, biochemistry and genetics to understand how SMC motors work, how they are controlled, and how they regulate gene expression.
The knowledge generated through this partnership will illuminate key questions in development and disease – how genes are turned on at the right time and in the correct type of cell and how the genes of invading viruses are silenced.
While these groups had not collaborated before, they are united by a shared history of uncovering a new principle of genome organization — loop extrusion — and revealing how it controls chromosome folding and function.
through large-scale computer simulations, the Mirny Lab (MIT) first proposed and demonstrated that loop extrusion is a central mechanism of chromosome folding throughout the cell cycle. The Dekker Lab (TU Delft) later confirmed this prediction with pioneering single-molecule experiments that directly visualized loop extrusion in action. The Bickmore and Rowland Labs (University of Edinburgh and Netherlands Cancer Institute) showed that this same process governs gene regulation and chromosome compaction inside cells.
Now, these teams have joined forces to understand the inner workings of SMC molecular motors that drive loop extrusion — how they generate force, how their activity is regulated, and how cells use them both to organize and to read their genomes, or to silence invading viral DNA.
Working closely with experimental partners, the Mirny Lab will develop biophysical models that reveal how SMC complexes perform persistent mechanical work to form chromatin loops thousands of times larger than themselves. The project also seeks to explain how these molecular machines can selectively silence viral genomes while fine-tuning gene expression in human cells.
The 2025 ERC Synergy grant round had a funding rate of just 9.6%. Professor Mirny would like to express deep gratitude to the many people at MIT who guided and assisted in the complicated process of submission: Katrina Norman and Tabitha Payson of IMES, as well as IMES Director Alex Shalek, Michael Leskiw of MIT Global Support Resources (GSR), Rupinder Grewal of the Office of the Vice President of Research (VPR), Provost Anantha Chandrakasan and the office of Research Administration Services (RAS).