Microtubule organizing centers (MTOCs) are eukaryotic cellular structures that nucleate microtubule formation and organize microtubules in 3D space. The poles of mitotic and meiotic spindles define a specific class of MTOCs called centrosomes. Cell cycle control of centrosome assembly is an important event that ensures that centrosomes are duplicated only once per cell cycle so a normal bipolar spindle is formed. Besides chromosome replication, this is the only precise duplication event during the cell cycle. The primary focus of the Winey lab is to understand the mechanisms underlying centrosome duplication. We are also interested in identifying centrosome components and understanding how these structures function in microtubule nucleation, in microtubule organization, and in other cellular processes.

Understanding the assembly and function of MTOCs has important implications in human health. In vertebrate cells, the primary MTOC is the centrosome. Defects in centrosome duplication and aberrant centrosome function appear to cause genomic instability that may contribute to cellular transformation. These defects are frequently observed in tumor-derived cells. Furthermore, centrosome aberrations likely contribute to defects in meiotic spindles causing chromosome missegregation, possibly the most significant origin of miscarriages. A centrosome is comprised of two centrioles (a radial array of 9 triplet microtubules) embedded in pericentriolar material, from which microtubules are nucleated. Centrioles share the same structure as basal bodies, the MTOC of cilia and flagella. In fact, the primary cilium in vertebrate cells is formed from one of the centrioles in the centrosome acting as a basal body. There are several, often pleiotropic, human diseases that arise from ciliary defects. Some of the genes mutated in humans that give rise to these diseases encode proteins found at basal bodies and centrioles. Therefore, the study of MTOCs will impact our understanding of cancer, meiotic chromosome missegregation, and ciliary diseases.

The Winey lab studies the assembly of MTOCs using two different cell types. We study the centrosome of the genetically tractable budding yeast S. cerevisiae, which is called the spindle pole body (SPB). Our work has identified conserved components of centrosomes, as well as conserved regulators and regulatory mechanisms for their assembly. While the SPB in yeast contains several widely conserved centrosome components, it lacks centrioles and thus lacks components required to assemble centrioles (and basal bodies). In order to identify and analyze proteins specific to centrioles/basal bodies we study basal bodies in the ciliate Tetrahymena, a tractable microbial system.  Much of our current work centers on proteomic approaches to identifying of MTOC components and the modifications of these components involved MTOC assembly or function.

This electron micrograph (by Tom Giddings, Jr.) shows the yeast Saccharomyces cerevisiae Spindle Pole Body (SPB), the functional equivalent of the centrosome in mammalian cells. The SPB forms the poles of the mitotic spindle and is required for accurate chromosome segregation in both mitosis and meiosis. In each cell cycle, along with DNA replication, the yeast cell must duplicate its SPB once and only once in order to form the bipolar spindle. Understanding how duplication of the SPB occurs is the one of the primary aims of the Winey lab.