Tony Bretscher is a Professor of Cell Biology in the Department of Molecular Biology and Genetics. He is a member of the Graduate Fields of Biochemistry, Molecular and Cell Biology, and Genetics and Development. After training as a physicist at the University of Cambridge, he obtained his Ph.D. in genetics from the University of Leeds, studying gene regulation in E. coli. From there he went as an EMBO Fellow to the Department of Biochemistry, Stanford University, where he worked with Dale Kaiser on the genetics of cell-cell interactions during development in Myxococcus xanthus. He then went as a Max Planck Society Fellow to the Department of Biochemistry, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany, where he began his studies in cell biology with Klaus Weber. In 1980 he was appointed to the faculty in the Cell Biology Department at Southwestern Medical School in Dallas, Texas. He moved to Cornell in 1981. He has served on the Editorial Boards of the Journal of Biological Chemistry and Molecular Biology of the Cell, and is currently on the Editorial Boards of the Journal of Cell Biology and Journal of Cell Science.
We are interested in the functional organization and regulation of microfilaments in eucaryotic cells. Microfilaments, which are composed of actin filaments and associated proteins, are involved in a host of functions, including the determination of cellular shape and providing the machinery for a variety of motile processes. We are using diverse biochemical, structural, genetic and cell biological approaches to investigate the general principles underlying microfilament structure and function in eucaryotic cells. Two major projects are underway.
The first is a detailed investigation into the molecular organization of the microfilaments that make up the cytoskeleton of microvilli present on intestinal epithelial cells. In this work we are purifying and characterizing the various microfilament-associated proteins (including villin, fimbrin, brush border myosin I, and ezrin) and, together with ultrastructural studies, are piecing together the precise function of each component. We then explore whether related proteins perform similar functions in other, less easily studied, microfilament arrangements. Current studies suggest that ezrin performs a central role in coordinating cell structure with membrane traffick in the apical aspect of epithelial cells.
The second major project exploits the yeast Saccharomyces cerevisiae for a combined biochemical and genetic approach to the structure and function of a microfilament in this simple eucaryote. We are presently identifying, purifying and characterizing microfilament-associated proteins related to those under study in higher eucaryotic cells. Over the last few years, we have shown that one major component of the yeast actin cytoskeleton, namely the polarized actin cables that run from the bud into the mother cell, are polarized highways for the delivery of secretory vesicles for cell growth, as well as providing the underlying polarity for organelle segregation during the cell cycle. Working with the actin cables is a myosin-V molecular motor that carries cargoes along the cables to their destination. Our goal is to understand at the molecular level how cables are established, and how they are used by the myosin-V to deliver their cargo, both of which have to be regulated in a cell cycle-dependent manner.