Molecular motor proteins are fascinating enzymes that power much of the movement performed by living organisms. In the first part of this lecture, I will provide an overview of the motors that move along cytoskeletal tracks (kinesin and dynein which move along microtubules and myosin which moves along actin). The main focus of this lecture is on how motor proteins work. How does a nanoscale protein convert energy from ATP hydrolysis into unidirectional motion and force production? What tools do we have at our disposal to study them? The first part of the lecture will focus on these questions for kinesin (a microtubule-based motor) and myosin (an actin-based motor), since they have been the subject of extensive studies and good models for their mechanisms have emerged. I conclude by discussing the importance of understanding motor proteins for human disease, in particular illustrating a recent biotechnology effort from Cytokinetics, Inc. to develop drugs that activate cardiac myosins to improve cardiac contractility in patients suffering from heart failure. The first part of the lecture is directed to a general audience or a beginning graduate class.
In the second part of this lecture, I will discuss our laboratory’s current work on the mechanism of movement by dynein, a motor protein about which we still know very little. This is a research story in progress, where some advances have been made. However, much remains to be done in order to understand how this motor works.
The third (last) part of the lecture is on mitosis, the process by which chromosomes are aligned and then segregated during cell division. I will describe our efforts to find new proteins that are important for mitosis through a high throughput RNAi screen. I will discuss how we technically executed the screen and then focus on new proteins that are we discovered that are involved in generating the microtubules that compose the mitotic spindle. I also discuss the medical importance of studying mitosis, including the development of drugs targeted to mitotic motor proteins, which are currently undergoing testing in clinical trials.