The Molecular Basis of Microtubule Structure and Dynamic Instability

Dynamic instability is the signature behavior of microtubules. In cells and in vitro, a steadily growing microtubule can suddenly switch to shrinkage in an event known as a “catastrophe.” Our textbook-level descriptions of dynamic instability have recently been upended by crystal structures and biochemical experiments that discovered new structural transitions in tubulin. These transitions are clinically relevant: microtubules are also the target of chemotherapeutics known as microtubule-targeting agents (MTAs), whose mechanism of action is to modify these newly discovered structural transitions. Our recent work has included the characterization of a novel MTA, as well as comparison of dynamic instability from diverse eukaryotes. I will discuss my lab’s recent efforts to use our knowledge of dynamic instability to promote safer chemotherapeutics and rebuild our textbook-level descriptions of microtubule growth and catastrophe.