Grant: Catalyst Grant - CEEHRC Epigenetics, Environment & Health

The current revolution in understanding the role that genes play in health and disease is being played out in the environment, that is: how the environment and events we experience can powerfully modulate our gene function and impact our response to life's challenges. To best understand the biology and genetics of this revolution that is called epigenetics, a model system needs to be established that best mirrors the human condition. The mouse has been the organism of choice to examine the role of genes in development and function. Therefore, we propose a set of studies that will lay the groundwork to use the powerful biological reagents in the mouse to understand how epigenetic changes can be cell and tissue specific. We will further examine how environmental perturbations, like the restriction of nutrients to the embryo that is being played out in millions of pregnancies throughout the world, greatly affects brain development and function. We will use an inbred strain of mouse that has been the focus of extensive genetic analysis to determine how the constellation of epigenetic "marks" differ from one cell type to another (eg, brain to blood) to appreciate common and different changes between tissue types. We have developed a mouse model of intrauterine growth restriction (IUGR) and shown that a part of the brain, the cerebellum, is sensitive to IUGR. As such, we will examine the extent to which the effects of IUGR on brain development are due to epigenetic changes. Finally, we will work with a biotech company, Illumina, to help generate a microarray-based chip to efficiently and effectively identify alterations in the mouse epigenome. Ultimately, our goal is to provide an understanding of how debilitating epigenetic alterations can be reversed by establishing the mouse as our preclinical model and translating our findings into the human population.