Examining the programming of offspring behaviour by maternal diet and abnormal maternal care
There is a well-defined association between early life adversity (either prenatally or in early childhood) and significantly poorer outcomes for children.
Exposure of the developing fetus, for example to poor diet, maternal depression or stress, and/or exposure of very young children to suboptimal maternal care has life long consequences including the increased occurrence of ADHD, depression and schizophrenia. Dissecting apart the relative contributions of these adversities is challenging in human cohort studies. We have developed a novel model in which exposure to a low protein diet during pregnancy results in the aberrant expression of an imprinted gene in the placenta. We know that this gene is involved in the instruction of maternal care and that very young children with this same change in their placenta show higher levels of aggression. Funded by an MRC grant, we are currently exploring the relevance of this specific placental alteration to maternal behaviour in a novel in vivo experimental model. This PhD project will explore the behavioural phenotype of the offspring from this model. The student will characterise the behaviour of genetically modified offspring, which have already been shown to be less exploratory and more aggressive. The student will then utilise molecular techniques to characterise the temporal sequence of events leading to changes in the brain structure and apply a novel in vivo imaging technique to visualise and quantify ongoing neurogenesis. Finally, the student will use cross-fostering studies to ask whether the abnormal behaviour and brain changes in the offspring are due to in utero exposure to a poor diet or post natal exposure to poor maternal care. This work will be translated back to the clinical setting in a follow up study of the Grown in Wales cohort.
This is a multi-discipline study that requires an understanding of the molecular and behavioural neuroscience. Students will gain experience of the following: analysing gene expressing by RNAseq and QPCR, fluorescence microscopy; using in vivo imaging to assess neurogenesis; the use of behavioural techniques such as social interaction monitoring and motoric function analysis as well as basic animal husbandry/welfare and colony management.
Please contact Professor Rosalind John (JohnRM@cf.ac.uk) for further details of this project and other opportunities with the Pregnancy Epigenetics Research Group.