Research Fellows Directory
Dr Joanna Rakoczy
University of Cambridge
The epigenetic effects of abnormal folate metabolism on fetal and placental development
Mounting evidence suggests that exposure to stressors (e.g., poor nutrition) can influence our epigenomes leading to increased disease risk in adult life. We are only now beginning to understand that this disease risk may be inherited by subsequent generations through non-conventional modes of inheritance called epigenetic inheritance. To explore this phenomenon, I will utilise a unique genetic mouse line (Mtrr) in which normal folate metabolism is disrupted. Folate is required to donate one-carbon methyl groups to DNA and histones. The Mtrr mouse model displays congenital defects (e.g., neural tube, heart and placental defects) similar to those seen in maternal folate deficiency in humans. Remarkably, the phenotypes in the Mtrr model are transgenerationally inherited by the wildtype grandprogeny. Together, the ancestral and direct roles of folate metabolism during feto-placental development remain unclear. Using genetic, cellular and embryo manipulation techniques in the Mtrr model, I will investigate the transgenerational effects of folate metabolism on feto-placental development. Understanding the long-term effects of folate deficiency will influence how we think about disease inheritance in humans.
Interests and expertise (Subject groups)