Main Body

Investigators and Program Directors

Research Interests

The focus of our laboratory is on how the mitotic spindle forms and functions to move the chromosomes during mitosis in vertebrates, and how progress through this part of the cell cycle is regulated. Since the spindle consists primarily of centrosomes (spindle poles), kinetochores, microtubules, and chromosomes the structure, composition and behavior of these organelles is actively investigated. One recent emphasis has been to better define how kinetochores behave during spindle assembly in living cells. From this work we have generated the best model to date on how the forces for chromosome motion are balanced and regulated so that the chromosomes become positioned on the equator of the forming spindle. We have also shown that kinetochores release an inhibitor of the metaphase/anaphase transition when they are not properly attached to the spindle, and that this inhibitor targets a complex associated with the spindle.

We are also actively studying the structure, composition and function of centrosomes in animal cells. Some of this work is done in collaboration with colleagues throughout the world, and it relies on our unique ability to generate high-resolution 3D tomographic reconstructions of centrosome structure in vivo and in vitro. Recently we have devised a novel technique, based on laser microsurgery and GFP-gamma-tubulin labeling, that allows us to selectively remove one or both centrosomes from a living cell. It is anticipated that this exciting development will allow us to unambiguously determine the role of the centrosome in cell cycle progression and spindle assembly in vertebrate cells.

For most of our studies we follow living cells by video enhanced light microscopy, and then analyze this data with computers. In many cases we also fix the cell at a desired time for corresponding 3D ultrastructural analyses in order to determine the underlying structural correlates that define behavior. We also use low-light level imaging modes to determine the changing distribution of various fluorescently-tagged cytoskeletal proteins in vivo, including GFP-gamma-tubulin. Recently we constructed a laser-based microsurgery and optical trapping system that allows us to destroy specific mitotic organelles in living cells, including centrosomes or kinetochores, and/or to manipulate them within the cell. Finally, we also have the capacity to generate high resolution 3D fluorescent images of living or fixed cells by deconvolving serial optical sections, and this methodology is currently being used to study various aspects of spindle formation and chromosome positioning.

Contact Information

E-mail: rieder@wadsworth.org
Phone: (518) 474-6774
Fax: (518) 486-4901