Cytoplasmic dynein drives long-distance transport along microtubules, but how motor complexes adapt to mechanical loads and coordinate their activities remains poorly understood. I will present our discovery that the dynein–dynactin–BicD2 (DDB) complex dynamically recruits a third dynein under load through an auxiliary BicD2 adaptor that interacts with the dynein light intermediate chain (LIC), increasing force generation from 7 to 9 pN. I will also show how our investigation of the neurodevelopmental disease-associated DYNC1H1 mutation P3018S revealed that the trailing dynein determines the velocity of multi-dynein complexes, while the leading dynein stimulates the trailing motor through its LIC. Together, these findings uncover unexpected roles for LICs in load-dependent motor recruitment and inter-motor communication, establishing new principles of dynein force adaptation and coordination.


The Gennerich Lab investigates the molecular mechanisms by which biomolecular motors generate force and motion in eukaryotic cells. We focus on understanding how defects in these processes contribute to human disease. Our research combines single-molecule biophysics, molecular biology, and biochemistry to study the function and regulation of microtubule-based motors—kinesins and cytoplasmic dynein—as well as RNA polymerase II during transcription elongation through chromatin.

Using a multidisciplinary approach that includes high-resolution optical trapping, single-molecule fluorescence microscopy, and CRISPR-Cas9-based genetic tools, we dissect how these motor proteins convert chemical energy into mechanical work and how their activity is modulated in different cellular contexts. Our long-term goal is to uncover the design principles of biomolecular motors and to elucidate the molecular basis of diseases caused by impaired motor function.