Dr Erica Watson

Epigenetic changes accrued in the genome throughout one’s lifetime can contribute to an increased risk for disease. These changes may occur through exposure to environmental stressors (e.g., toxins, nutrient deficiency, etc.) that alter epigenetic factors, such as patterns of DNA methylation, ultimately causing gene misexpression. Exposure to these environmental factors in utero may alter epigenetic programming, such that the nine months before you are born may have a profound impact on your health later in life. Mounting evidence also indicates that maternal, paternal or even grandparental exposure may contribute to congenital malformations and/or metabolic and cardiovascular diseases in children and grandchildren. This non-conventional inheritance occurs via epigenetic rather than genetic inheritance, and implicates the germline. Very little is understood regarding transgenerational mechanisms of inheritance. Our aim is to explore how developmental abnormalities and disease risk is epigenetically transmitted between generations. Further understanding this mechanism will drastically impact human health.

The Watson lab currently explores the mechanisms behind the transgenerational epigenetic effects of folate metabolism during fetal and placental development. Folate is a vitamin important for the one-carbon metabolism and methylation of cell components (e.g., DNA). To study this, they use a genetic mouse model with a mutation in a key gene involved in folate metabolism (Mtrrgt) that disrupts folate metabolism and results in similar metabolic effects as human folate deficiency. They recently showed using highly controlled genetic pedigrees that when either maternal grandparent carried the Mtrrgt mutant allele, it was sufficient to cause developmental abnormalities and epigenetic instability in their grandprogeny at midgestation (Padmanabhan et al, 2013 Cell). This occurred even when the mother and the grandprogeny are genetically wildtype for the Mtrr mutation. Some of the abnormalities (e.g., neural tube, heart and placental defects) persisted after embryo transfer experiments and for up to 5 generations, implicating epigenetic inheritance as a mechanism.

The goal of their current research goal is to use the Mtrr mouse model to understand the molecular mechanism behind the transgenerational effects of folate metabolism on development by breaking it down into the specific properties of each generation (i.e., grandparental, maternal and placental/embryonic effects) using epigenetic, molecular and embryo manipulation techniques. Ultimately, this will help us explain the role of folate metabolism during development and provide clues as to how transgenerational inheritance of disease and phenotypes is achieved.

Dr Claire Senner (Next Generation Fellow, CTR)

Charlotte Handford (PhD student [co-supervised by Magdalena Zernicka-Goetz], CTR studentship)

Amy Wilkinson (PDN Part II student)

**We are recruiting a postdoc! Details are to come. Please email Dr Watson for information**

***Prospective graduate students, please email Dr Watson***