Grant: CIHR Fellowship

The rapid rise in the incidence of heritable disorders (e.g. diabetes and obesity) with limited evidence for a genetic basis has become a topic of significant empirical and clinical interest. The aim of this fellowship is to investigate the role of non-genetic/epigenetic factors (i.e. DNA methylation and small non-coding RNAs (sncRNAs)) in the inheritance of acquired traits. Specially, we wil be using an established and clinically relevant mouse model of fetal undernourishment which results in metabolic dysfunction and the development of obesity. In the first set of experiments, I will profile the RNA content of adult sperm of fetally undernourished males to determine if this manipulation induces changes in the expression of epigenetic factors across multiple generations. Following this I will measure the reversibility of such effects using postnatal feeding interventions to prevent the development and transmission of disease phenotypes to subsequent generations. These studies will be undertaken with the help of state-of-the-art sequencing technologies and advanced bioinformatic tools, to reveal genome-wide patterns of epigenetic marks and non-genetic signals within the germline that contribute to the heritability of fetal undernourishment. Together, the experiments will answer important questions about epigenetic inheritance of disease processes and shed light on their broader evolutionary and clinical significance in animal and human populations.