Transgenerational epigenetic inheritance modulating brain function, behaviour and cognition
The study of how environmental exposures and experiences affect sperm RNA and DNA as well as behavioural, cognitive and other phenotypes is still in its infancy. In particular, the growing prevalence of some brain disorders implicates environmental factors (as genomes evolve very slowly), and these could be acting at least partly via epigenetic inheritance, including both the maternal and paternal lineages.
Using pre-clinical models we explore sperm epigenetics as well as intergenerational and transgenerational epigenetic inheritance. The period of adolescence, the transition time from childhood to adulthood, is a critical phase for the developing organism. During this time, substantial remodelling of the brain occurs in response to hormonal and physical changes. Hence, the brain is particularly sensitive to external influences, including environmental exposures that alter experience. These paternal exposures can lead to alterations in sperm non-coding RNA levels and DNA methylation. Although there are recent indications from our lab and others that paternal environmental exposures can epigenetically affect some aspects of the offspring phenotype, the mechanisms are unclear.
This project aims to study the impact of environmental interventions on male laboratory mice and their female and male offspring. To achieve this goal, fathers are exposed to different environmental conditions and their offspring are assayed using a variety of behavioural tasks as well as cellular/molecular approaches, to gain a comprehensive picture of offspring endophenotypes. We also use cutting-edge epigenetic approaches to elucidate the modulation of the sperm epigenome and offspring development, physiology and metabolism.
Due to the high translational value of this project, the results will be crucial to our understanding of the of the epigenetic intergenerational impacts of paternal experience on molecular and cellular mediators of brain function, cognition and behaviour.
Take part in this project
Students who are applying to study at The Florey can register their interest in this project. Refer to our step-by-step guide to help you with your application.