Prof. Jonathon Howard

Our laboratory is interested in the mechanical properties of cells and molecules. How do cells detect and effect changes in their mechanical environment? How do they establish and change shape? How do they move?

To answer these questions, we havedeveloped highly sensitive techniques that allow us to visualize and manipulate individual molecules, and to measure directly the influence of forces on their structural conformations. Using these techniques, we have measured the force required to open a single ion channel, we have determined the elasticity of individual cytoskeletal filaments, and we have characterized the mechanical output - the force, displacement and work - of single motor proteins.

Current projects in the lab include the following:
(i) The molecular mechanisms of force generation by motor proteins. By combining single-molecule techniques with biochemical and protein-engineering methods, we hope to identify, at the amino acid level, the moving parts that make up motor proteins - the springs, shafts, and axles - and to understand how the motion of these parts is coupled to the hydrolysis of ATP.

(ii) The structural basis for the regulation of motor proteins. We are trying to understand how motor proteins recognize and bind to their cellular cargoes, and how the binding to the cargo leads to the switching on of the motor activity.

(iii) Mechanoelectrical transduction by cutaneous sensory receptors. We are studying the cellular and molecular mechanisms underlyingthe sensation of touch to the skin: which cells are mechanoreceptive, what molecules and structures are initially perturbed by the mechanical stimuli, and which ion channels are ultimately gated by these mechanical forces?

(iv) Remodeling of the extracellular matrix. How do cells such fibroblasts reorient in response to forces in tissues and how, in turn, does this lead to a reorientation and polarization of the extracellular matrix.