Researchers

Professor Goodson's interests address the broad problem of how living cells achieve and maintain internal organization. The precise and often beautiful arrangement of subcellular components provides the foundation for control of processes such as cell motility, response to physiological stimuli, and the growth and development of multicellular organisms. Defects in normal organization are key hallmarks of cancer. A central component of cell organization in eukaryotes is the cytoskeleton, the dynamic framework of structural proteins which gives cells their shape and motile properties. The cytoskeleton plays an essential role in determining the location and functionality of internal membranes and organelles.

The research in the Goodson laboratory is directed at two main questions. First, how is the dynamic morphology of the cytoskeleton itself achieved and maintained? In more experimentally tractable terms, how do specific activities of specific proteins alter the assembly behavior of cytoskeletal proteins? Second, how is cytoskeletal structure and order translated into organization of other components, particularly membranes? In other words, which proteins are involved inmembrane-cytoskeleton interactions, and how are these interactions regulated?

Current research is focused on CLIP-170, a protein which appears to play a role in the answer to both of these questions. CLIP-170 is a "cytoplasmic linker protein" which binds to the microtubule cytoskeleton and is involved in interactions between endosomal membranes and microtubules. In addition, CLIP-170 can enhance microtubule assembly and localizes specifically to the growing plus end of microtubules, the site at which microtubule dynamics are thought to be regulated. In order to dissect both the role of CLIP-170 in membrane-microtubule interactions and the mechanism by which it affects microtubule assemble, we are using a multifaceted approach consisting of classical biochemistry and in vitro assays, cell biological techniques (including in vivo imaging), and modern molecular biology. CLIP-170 is just one member of a larger family of CLIP-170-related proteins ("ClipRs"). Because it is likely that these ClipR proteins will also have roles in membrane-microtubule interactions and/or regulation of microtubule function, additional projects in the lab will focus onthe identification and characterization of new ClipR proteins.

A second area of interest in the Goodson laboratory is molecular evolution, with emphasis on using evolutionary relationships within protein families to address questions of protein function. For example, genome projects have revealed that most proteins are members of large families, but how far can we go in the assumption that characteristics of one family member are true for another? Determination of the evolutionary relationships between family members by phylogenetic analysis of the protein sequences can provide many answers. Past projects have included analysis of the myosin and kinesin motor superfamilies. Present efforts are focused on expanding the application of computational phylogenetic techniques to the study of protein structure/function relationships.