Reduced placental amino acid transport in fetal growth restriction: exploring regulatory mechanisms

An appropriately functioning placenta is key to a successful pregnancy. The placenta represents the interface between mother and developing fetus and one of its key roles is supplying nutrients such as amino acids to support fetal growth. When placental function is compromised, termed placental dysfunction, nutrient transfer to the fetus becomes sub-optimal and reduced fetal growth is the end result. Placental dysfunction is thus the major cause of fetal growth restriction (FGR), the failure of a fetus to achieve its genetic growth potential. FGR occurs in ~5% of pregnancies in the UK and is a major risk factor for stillbirth. Additionally, babies that are growth restricted have an increased risk of developing a number of childhood and adulthood diseases. Despite these devastating consequences of FGR, there is no current treatment. In severe cases of FGR, the baby is often delivered prematurely which is itself linked with increased rates of morbidity and mortality in the short and long-term.

One of the reasons why there are no current therapies for FGR is that the mechanisms underlying placental dysfunction
remain largely elusive. Whilst we do know that placental transport of key amino acids for fetal growth are reduced in FGR we do not fully understand the mechanisms underpinning these observations. This project, through the use of nutrient transfer studies on human placenta and by the use of molecular biology techniques, will explore the mechanisms responsible for reduced placental amino acid transport in FGR in order to identify novel therapeutic avenues for this pregnancy complication. This project will be based within the Maternal and Fetal Health Research Centre, the largest pregnancy-based research group in Europe which consists of a team of scientists, clinicians and midwifes all working towards ‘finding solutions to pregnancy problems’.

This PhD will be based within the Maternal and Fetal Health Research Centre which brings together over 70 researchers. The centre has an excellent reputation as an outstanding training environment. The successful PhD candidate will form part of a collaborative, multi-disciplinary research team and would gain an excellent portfolio of techniques including the handling and sampling of human placental samples, cell culture, microscopy and studies assessing radiolabelled uptake of amino acids. Additionally, a host of molecular techniques including Western blotting, quantitative PCR and siRNA transfection will be employed. As part of this PhD, the candidate will also be enrolled into the university’s successful doctoral training programme and receive training in generic research skills including having the opportunity to present their data at national/international meetings. They would also have the opportunity to gain experience in undergraduate teaching and public engagement activities for which the centre has a burgeoning reputation.