The Dodding and Woolfson labs (Schools of Biochemistry and Chemistry, University of Bristol) have been awarded a grant by the BBSRC to understand how the kinesin-1 microtubule motor is activated, and to design new peptide-based-reagents to enable control of its activity.
Kinesin-1 motors play critical roles in intracellular transport of vesicles, organelles, protein complexes and mRNAs. They are particularly important for transport within the neuronal axons, and are dysregulated in many neurodegenerative diseases.
This four-year award, commencing in 2025, builds on their existing collaboration and will support two postdoctoral scientists working between the two labs.
For this project (Mechanism and design of allostery in the kinesin-1 complex), the team will aim to obtain a deep mechanistic understanding of the kinesin-1 autoinhibitory mechanism; insight into how cargo engagement induces conformational changes in the complex; and a clear understanding of the nature of active motor-cargo complexes. They will apply the latest protein/peptide design approaches to identify strategies and targets for manipulating kinesin activity, setting the stage for future work to apply these technologies to finely control kinesin-mediated transport in disease states.