The Howard laboratory is interested in the biochemical and biophysical basis of cell shape and motion. The shape of a cell is determined primarily by its cytoskeleton, which serves as a scaffold to support the plasma membrane and internal organelles. The cytoskeleton also serves as a network of tracks along which motor proteins transport subcellular structures. The research is therefore focused on the mechanics of the cytoskeleton, with a particular emphasis on microtubules and microtubule-based motor proteins.

On the one hand, the laboratory is interested in the mechanisms by which these proteins work: i.e. how do kinesins and dyneins act as molecular machines to convert chemical energy derived from the hydrolysis of ATP into mechanical work used to move along or to depolymerize microtubules? And on the other hand, it is interested in the roles that microtubules and their motors play in cell morphology and motility. For example, how do the dynamic properties of microtubules drive spindle and chromosome movements in mitosis, and how does dynein drive axonemal motility? What roles do microtubules and their motors play in mechanoreception in sensory cells and in determining the shapes of cells?

What makes these problems so fascinating is that somehow molecules, whose dimensions are nanometers, coordinate the assembly and movement of structures whose dimensions are on the order of the size of the cell, some thousands to millions of times larger than molecular dimensions. Our approach to understanding the self-organization of molecules into  organelles and cells 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. We use theory to predict how the interactions lead to the collective behavior of ensembles of molecules, and then to test these predictions with in vivo experiments.

To address these issues, the Howard lab combines several techniques - single-molecule fluorescence, optical 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.