My lab is interested in the biochemical and biophysical basis of cell shape and motion. What makes this problem so fascinating is that somehow molecules, whose dimensions are nanometers, coordinate the assembly and movement of cells, whose dimensions are thousands to millions of times larger. What are the organizing principles?

Our research is focused on the mechanics of the cytoskeleton, especially microtubules and microtubule-associated proteins (MAPs). On the one hand, we are interested in how these proteins work as molecular machines. How do motors and other MAPs regulate the dynamical properties of microtubules? On the other hand, we are interested in how microtubules and motors move and shape cells. For example, how do the dynamic properties of microtubules drive spindle and chromosome movements during mitosis, and how does dynein drive axonemal motility? How do cell sense force?  

Our general approach is to characterize the interactions between the individual motor and cytoskeletal molecules in vitro using single-molecule techniques. These interactions constitute a form of mechanical signaling (Howard 2009). We then use theory, primarily from statistical physics, to predict how the interactions lead to the collective behavior of ensembles of molecules. We then test these predictions with in vivo experiments, which are analyzed using image processing techniques.

The Howard lab uses many techniques: single-molecule fluorescence, optical and magnetic tweezers, image processing, modeling, molecular biology, nanofabrication and nanofluidics, and electron microscopy. The work benefits from close collaborations with theoretical physicists from the MPI for the Physics of Complex Systems.

Single Kip3 motors (kinesin-8 family), shown in green, moving along a microtubule, shown in red. Kip3 is the most processive cytoskeletal motor known: it can take up to 5,000 8-nm steps along a microtubule without dissociating.