WCPRS/BORNECharity PhD Studentship

A collaboration between the Division of Translational and Systems Medicine, Warwick Medical School and BORNE,-the charity that translates research into health new life.

Project Title:

Maternal stress and placental adaptive responses associated with adverse pregnancy outcomes

Prenatal environmental exposures can have sustained effects across the lifespan. This is attributed to activation of maternal disease-triggered adaptation mechanisms that influence fetalgrowth and neurodevelopment. During this period of vulnerability a range of exposures have been found to exert long-term changes on fetal physiology, brain development with implications for physical, behavioural and mental health. For example, extreme states of maternal nutrition are associated with deranged fetal growth and birth weight, which is linked to increased prevalence of insulin resistance and/or hypertension, affective and neuro-developmental disorders later in life. This is of particular importance for understanding the pathological sequelae of obesity and diabetes that affects about 15% of all pregnancies and is now a major health priority in the Western world.

It is increasingly recognized that perturbations in the maternal environment are conveyed to the fetus by changes in placental function that involve (poorly understood) placental stress responses. In this research framework the biological role of specific placental sensors such as O-GlcNAc transferase (OGT) in states of common maternal disease such as obesity-diabetes, is emerging as a crucial research target.

OGT catalyses the addition of an O-linked N-acetylglucosamine (O-GlcNAc) moiety to the hydroxyl groups of Ser/Thr residues of target proteins. OGT and protein O-GlcNAcylation appears to act as a cellular sensor of stress and its blocking or reduction renders cells more sensitive to stress and decreases cell survival; in contrast increased O-GlcNAc levels protects cells.Placental O-GlcNAc transferase (OGT) plays a crucial role in fetal neurodevelopment and its maternal stress-induced downregulation appears to be involved in impaired neurological development of the offspring.

The purpose of this project is to investigate:

-placental OGT pathways and downstream biological responses that are targeted by distinct maternal homeostatic perturbations such as obesity-induced diabetes and perinatal depression.

-fatty acid metabolism in rodent models of HFD-induced obesity.

-The impact of adaptive responses to circadian patterns in a metabolically compromised environment in pregnancy focusing on characterization and clock genes in the brain, adipose tissue and placenta.

The research project cuts across and brings together key strategic research priorities of WMS, metabolic health and reproduction and development.Maternal metabolic disease is associated with deranged fetal growth and birth weight, which is linked to increased prevalence of insulin resistance and/or hypertension, affective and neuro-developmental disorders later in life. This research is of particular importance for understanding the pathological sequelae of obesity and diabetes that affects about 15% of all pregnancies and is now a major health priority in the Western world.

The successful candidate will develop expertise in in a wide variety of in vivo and in vitro molecular and cellular research methodologies to understand the molecular basis of disease associated with metabolic challenges during pregnancy and impact on fetal development and use of animal models of disease

The successful candidate will join a vibrant and expanding research team at the University of Warwick within the Division of Translational and Systems Medicine.

At Warwick the academic supervisors will be Professor Dimitris Grammatopoulos, Professor of Molecular Medicine and Professor Victor Zammit,Division of Translational and Systems Medicine, Warwick Medical School, in collaboration with Professor Mark Johnson, Imperial College, London who will be the clinical academic mentor.

The successful candidate will be expected to start on 3rd October 2016 and will be located at Warwick Medical School, Clinical Sciences Research Laboratories at University Hospital Coventry and Warwickshire NHS Trust.

Applicants should have a good biomedical, physiology,neurosciences, molecular biology, lifesciences degree.

This studentship is available to Home and EU students, according to fee status, who meet Research Council eligibility requirements based on residency. The studentship includes full fees for the successful candidate along with a tax free maintenance allowance in line with Research Council UK standard stipend (£14,296 for the year 2016/17). The studentship also includes consumables funding.

The closing date for applications is 15hJune 2016. Interviews will be held on 20thJuly 2016 at the Clinical Science Research Laboratories in University Hospital Coventry and Warwickshire NHS Trust.

Please contact Professor Dimitris Grammatopoulos for further information about the research project:

Papers and a summary of the research group activity can be found here:

To formally apply, please send a copy of your Curriculum Vitae (CV) and a one page personal statement at early stating the studentship you are applying for.