Identification And Evolutionary Comparison Of Imprinting Centers
An intriguing characteristic of imprinted genes is that they often cluster in larger chromosomal domains that are regulated by imprinting centers. Comparative analysis of four imprinted domains in mouse and humans revealed that while there is some commonality, various silencing mechanisms are employed by different imprinting domains. Thus, despite the many advances that have been made since the identification of the first imprinted gene, the nature of the imprinting center and its mode of action have remained elusive. We will develop a novel procedure for the isolation of methylated sequences. Data generated from this study will allow comparative analysis of a larger number of imprinting centers and will lead to a greater understanding of the molecular mechanisms regulating imprinting and the evolution of genomic imprinting. Research Interests  Molecular Analysis of Genomic Imprint   Maintenance during Embryogenesis
       My research focuses on epigenetic mechanisms that control gene expression, specifically on genomic imprinting.  Genomic imprinting is defined as a mechanism of transcriptional regulation that restricts expression to one parental allele. Imprinting may be envisaged as a multi-step process that begins in the gametes, where epigenetic modifications differentially mark the parental alleles.  These marks must then be stably maintained in the developing embryo where they are translated into parental-specific expression.  Preimplantation development is a dynamic period of epigenetic change including chromatin remodeling and global demethylation.  Within this milieu, gametic imprinting marks must be preserved.  From my work in the mouse, I demonstrated that imprinting can be perturbed during preimplantation development by embryo culture.  These data indicate that mechanisms operate to maintain imprinting in the mammalian preimplantation embryo.  However, very little is known about these processes.  Research in my laboratory focuses on mechanisms that maintain genomic imprinting.  More specifically, we are investigating the molecular and developmental effects of in vitro embryo culture.  This research will further our understanding of epigenetic mechanisms involved in genomic imprinting during normal embryonic and fetal development, and will provide the biologic basis for crucial considerations relevant to the treatment of human infertility by ARTs. Ultrasound Biomicroscopy
Day 13.5 mouse embryo head. The image was obtained at the Imaging Research Laboratories at the Robarts Research Institute by Michael Bygraves, in collaboration with Dr. Aaron Fenster, Director and Canada Research Chair in Biomedical Engineering.