How does poor maternal diet affect foetal neural stem cell activity leading to adult behavioural disease?
Main Supervisor: Sandrine Willaime-Morawek
Other members of the supervisory team: Tom P. Fleming
Duration of the award: 4 years
Malnutrition, especially protein undernutrition, is the greatest threat to global public health according to the World Health Organization, affecting some 13% (1 in 7), 925 million people in 2010 and causing 54% of child mortality. Nutrition directly affects cell metabolism and growth. It is important therefore for women during pregnancy and lactation to ingest sufficient nutrients for themselves and their child to prevent the risk for abnormal development and disease in offspring as conceptualised in the Barker hypothesis.
Animal models of protein undernutrition produce effects similar to human health problems found in underdeveloped countries. Consequently, we have developed mouse models of maternal low protein diet (LPD) during either the entire gestation period or just during the periconceptional period (Emb-LPD), a developmental window we have shown to be particularly sensitive for long-term offspring health. Our models demonstrate adverse cardiovascular, metabolic and behavioural outcomes in adult offspring. The LPD challenge is recognised as a suitable model for developmental programming of disease and has been used extensively for almost 20 years across species and internationally.
Early studies using stringent malnutrition conditions over extended pre- and post-natal periods illustrate adverse effects on overall brain growth and cell cycle but underlying causes have received less attention. A large and dispersed literature suggests that an inadequate supply of any of a number of essential micronutrients during the early period of brain growth, as well as throughout life, can compromise optimal brain function by affecting both behavioural and cognitive activity. Neural development relies on the tight regulation of neural stem cell proliferation and differentiation to generate the appropriate number of progeny (neurons, glial cells) necessary to populate the nervous system. Once formed, the progeny migrate to their correct location to incorporate into the neural network itself. Our project will evaluate the effects of protein restriction on ‘upstream’ events in the development of the brain that we already know lead to adult offspring behavioural dysfunction. We propose that maternal LPD during gestation or just the periconceptional period (Emb-LPD) affects the development of the brain by disturbing the regulation of neural stem cells proliferation and differentiation across life. This may contribute to the behavioural phenotype in adult offspring and represent the origin of adverse postnatal neurobehavioral traits. The aims of the project are to define the effects of these diets on the development of the brain and the regulation of neural stem cells, at tissue, cellular and molecular levels.
Please contact Sandrine Willaime-Morawek [Email Address Removed] 023 80 79 61 07 if you have any questions.
The successful candidate is likely to have the following qualifications:
• A 1st or 2:1 degree in a relevant discipline and/or second degree with a related Masters
• Lab Experience ideally in the stem cells or neuroscience field
Administrative contact and how to apply:
Please complete the University's online application form, which you can find at
You should enter Dr Sandrine Willaime-Morawek as your proposed supervisor. To support your application provide an academic CV (including contact details of two referees), official academic transcripts and a personal statement (outlining your suitability for the studentship, what you hope to achieve from the PhD and your research experience to date).
Closing date: 4th Oct 2013
Interview date: 10th Oct 2013
Selected candidates will be contacted shortly after the closing date to confirm an interview on the 10th October.
Funding information: Research Council rate studentship (£13,726 for 2013/14) by the Wessex Medical Research / Rosetrees Trust, the funding does not cover tuition fees for international students.