Motor Proteins and Intracellular Organisation
We are investigating the mechanisms by which motor proteins generate movement and spatial organisation within living cells. We are also interested in how defects in these mechanisms cause human pathologies. To address these topics, our work combines structural biology, cell biology, and single-molecule approaches.
A main focus is on dynein and kinesin, families of microtubule-based motors that use ATP hydrolysis to transport cargoes and signalling molecules within the cell interior. Dynein and kinesin also have critical roles in assembling larger cellular structures, such as the mitotic spindle, cilia and flagella. Our current goals are to understand how dynein and kinesin work as individual motors, how they cooperate to form bidirectional transport systems, and how they selectively attach to cargoes. We are studying these questions using transport within cilia and flagella as a biomedically important model. Defective transport in cilia causes a variety of human disorders associated with vision impairment, skeletal abnormalities, cystic kidneys, and infertility, among other conditions. Core techniques in our research are cryo-electron microscopy (cryo-EM), in vitro reconstitution, cell biology, and single-molecule fluorescence microscopy.