Research in the Vale Lab:
Summary: The Vale Lab combines cell biological and biophysical approaches to understand spatial organization, movement, and signaling within cells. The lab integrates biochemical, structural, and microscopy-based approaches to study these questions at scales that span from atomic information of proteins to the behavior of cells in living organisms.
At the smallest scale, we wish to understand the detailed workings of protein machines. A particular focus of our lab is on microtubule-based "motor proteins" that convert energy from ATP hydrolysis into unidirectional motion and force. We have concentrated for many years on the kinesin motor protein although more of our current emphasis has shifted to dynein. We also are interested in understanding the mechanisms of various other proteins, including microtubule nucleating factors (augmin), microtubule regulatory proteins (severing proteins, end binding proteins), and the T cell receptor. Our approach towards dissecting how proteins operate is to reconstitute and study their activities using in vitro assays, and then apply a spectrum of biophysical tools (e.g. single molecule observation, spectroscopy) to peer into lives of these small machines. We also seek to obtain detailed structural information to generate models, which we gather from x-ray crystallography or electron microscopy. In all cases, we feel that it is essential to be able to produce recombinant proteins for structure-function studies. We then can generate hypotheses of how these proteins work, design new proteins with predicted new capabilities, and then test if these hypotheses are born out by detailed biophysical analyses of these engineered machines.
We also wish to understand how collections of protein machines function together to generate complex behavior in living cells. As examples, we are currently interested in how numerous proteins function in building the mitotic spindle, generate specific cell shapes, transport mRNAs, and produce signaling responses in T cells. In these efforts, we use various types of microscopy to analyze cell behavior in culture or in living animals, examine consequences of gene knockdown (RNAi), and also engineer cells that exhibit new properties by introducing specific genes.
View specific research areas on the links above.