Research group of Dr. Kentaro Nabeshima

Research group of Dr. Kentaro Nabeshima

From left to right: Kentaro Nabeshima, Carolyn Rae Dombecki, Eric Allen Stefanski, Elke Patricia Francine Klerkx and Jamie Kang.

Dr. Kentaro Nabeshima is an assistant professor in the Department of Cell and Developmental Biology at the University of Michigan.

Kentaro has long been fascinated with the beauty of chromosome structure and dynamics. As a graduate student in the laboratory of Dr. Mitsuhiro Yanagida at Kyoto University, Japan, he focused his Ph.D studies on mitotic chromosome dynamics in the fission yeast, S. pombe. Kentaro later developed a greater interest in meiosis, where chromosomes show more complex and intriguing behaviors. From 1997 to 2001 he investigated the dynamics of the meiotic homologous pairing of fission yeast in the laboratory of Dr. Hiroshi Nojima at Osaka University, Japan, in collaboration with Dr. Yasushi Hiraoka. In 2001, this interest led him to pursue postdoctoral research on homologous pairing in the nematode C. elegans in the laboratory of Dr. Anne Villeneuve at Stanford University. It was here that Kentaro developed new tools and resources for visualizing meiotic chromosome dynamics in fixed and live specimens and initiated a functional genomics screen for pairing genes. By exploiting high-resolution 3D microscopy and improving immunostaining methods, he succeeded in imaging the fine structure of chromosomes as they are remodeled during late meiotic prophase. In 2007, he started his own laboratory at the University of Michigan medical school.

In meiotic prophase, maternally- and paternally-derived homologous chromosomes engage in crossover recombination events, resulting in the exchange of genetic material and the formation of chiasmata that physically connect the homologs and ensure their segregation to opposite spindle poles at the first meiotic division. Prior to successful recombination, each chromosome locates, recognizes and associates with its homologous partner (homologous pairing) and this association is stabilized by the synaptonemal complex (SC). A failure in any of these steps can lead to chromosome rearrangement and/or nondisjunction, a leading cause of birth defects and miscarriages.

The Nabeshima lab focus their research on the mechanisms of chromosome dynamics required for successful meiosis and, in particular, for meiotic homologous pairing and SC formation during C. elegans meiosis.  Although these processes are essential for sexual reproduction, its molecular mechanisms are only just beginning to be understood and many basic questions remain unanswered. How do chromosomes move around in the nucleus in the search for their homologous partners? How do chromosomes recognize their homology? How do chromosomes keep homologous association and/or discourage non-homologous associations? How is the initial association and SC formation coordinated?

To address these fundamental questions, Kentaro and his colleagues use a simple, genetically tractable model organism, the nematode C. elegans, and they employ the following research strategies:
1) Functional genomics screens for C. elegans genes involved in meiotic homologous pairing.
2) High-resolution imaging and chromosome paints to investigate 3D chromosome organization.

Kentaro says “We use Volocity to render 3D images from a stack of optical sectioning fluorescent micrographs.  Specifically, we study the spatial organization of chromosomes in the nucleus using this software. Thread like chromosomes are intermingled within the small 3D space of the nuclei and Volocity, which allows us to visualize fine 3D structures, is essential.   Among many similar software packages, Volocity is one of the most powerful and user-friendly programs. We really like its flexibility, interactive interface and the instant reflection of new image display parameters to 3D rendered images; it can change these parameters even whilst rotating a rendered image, which is very useful for optimizing these parameters. The quality of the movies created by Volocity is also impressive and they have always entertained our audiences. We also appreciate the great customer care that is provided by the PerkinElmer (Improvision) technical support team”.

The movie shows chromosome painting in a whole-mount C. elegans gonad: White - DNA stained with DAPI; Green-Red-Blue - painting of chromosome II

 

To view more movies made using Volocity, and to find out more about research in the Nabeshima lab, please visit: http://www-personal.umich.edu/~knabe/