Hernando J. Sosa, Ph.D.

Assistant Professor
Office: ULL 217
Tel: 718-430-3451
Email: hsosa@aecom.yu.edu

In my laboratory we are interested in elucidating the structural basis of the mechanism of action of molecular motors with particular emphasis on motors of the kinesin superfamily. There are three main super-families of linear biological motors: myosins, kinesins and dyneins. These motors use the energy of ATP hydrolysis to move along cytoskeletal filaments, actin filaments in the case of myosins and microtubules in the case of dyneins and kinesins. The kinesin superfamily consists of more than 100 different proteins that power intracellular motile processes such as organelle transport and cell division. An understanding of the similarities and differences among kinesin motors may help developing more specific therapies against cancer. Today several anticancer drugs control the growth of cancer tissue by targeting microtubules. These drugs have undesirable side effects, as microtubules are an integral part of all eucaryotic cells.

A central problem in molecular biophysics is to understand the mechanism by which molecular motors convert the energy of ATP hydrolysis into mechanical work. However, a full understanding of the conformational changes that allow kinesin stepping along microtubules is lacking. It is also not clear what conformational differences account for the different behavior observed between members of the kinesin superfamily. Some kinesins move towards the microtubule plus end while others move toward the minus end. Some kinesins move processively (they are able to take many steps without dissociating from the microtubule) while others lack this ability. Also it is not clear how the kinesin motors interact with their cargoes. In my laboratory we seek to answer these problems using a combination of cryo-electron microscopy and fluorescence spectroscopy. Cryo-electron microscopy is an ideal technique to obtain medium to high resolution information of big macromolecular complexes such as the one formed by the kinesin motors and the microtubules. To trap different structural intermediates we use non-hydrolyzable ATP analogues and rapid mixing techniques. To detect conformational changes in aqueous solutions as the proteins work, we developed a fluorescence polarization microscope that allows determining the orientation of a single fluorophore.