Developmental and Endocrine Signalling Centre

The interests of the Centre members are focused on cellular signalling at different points in human development from the early stages of conception until old age. There are 10 group heads within the Centre and numerous fellows, postdoctoral research assistants, technicians and postgraduate students. Government and charitable organisations including the BBSRC, British Heart Foundation, MRC and the Wellcome Trust fund work within the Centre.

The life cycle starts with the work of Professor Saffron Whitehead and Dr Helen Mason who collaborate on many aspects of folliculogenesis and steroidogenesis focusing on polycystic ovary syndrome, a common problem within the local community. Professor Whitehead also has a major interest in the field of endocrine disrupting chemicals - particularly the dietary phytoestrogens and their effects on reproductive health and breast cancer.

This work on steroidal biochemistry in reproductive tissue is complimented by that of Dr Tony Michael who is researching the cellular control of steroid synthesis and the target cell metabolism of steroid hormones. He also has a subsidiary interest in the control of prostaglandin synthesis and metabolism, and steroidal modulation of prostaglandin action via GPCRs.  Most of the group’s research is conducted in reproductive tissues, particularly the ovary where research interests include the local control of oocyte maturation and development within ovarian follicles, while other ongoing projects involve cardiovascular and renal endocrinology.

The work of Professor Guy Whitley and Dr Judith Cartwright in collaboration with Dr Philip Dash (BHF Fellow) and Professor Alan Johnstone forms the core of the Reproductive and Cardiovascular Research Group. The main focus of the research is the vascular remodelling that occurs during placentation. During normal pregnancy trophoblast cells invade the uterus of the mother and remodel the spiral arteries thus ensuring a sufficient blood supply to the baby. In pre-eclampsia, a major cause of maternal and perinatal morbidity, trophoblast cells show poor invasion of the uterus. The group have been investigating the regulation of trophoblast invasion, motility and apoptosis and have characterised the involvement of growth factors and nitric oxide in these processes. Professor Johnstone and Dr Cartwright also collaborate on projects relating to the complex control of maternal immune responses that allow a successful pregnancy to develop, including determination of the molecules involved in interactions between maternal myeloid cells and fetal trophoblast cells. Professor Whitley also has interests in the regulation of nitric oxide synthesis in particular by asymmetric dimethylarginine an endogenous inhibitor and the enzyme dimethylarginine dimethylaminohydrolase and their role in pre-eclampsia.

Aspects of embryological development are the focus of Professor Nigel Brown’s group particularly as regards to early development of the heart and congenital malformation. The molecular mechanisms leading to left-right asymmetry has been a special interest for a number of years. In addition Professor Brown is also involved in research into developmental toxicity of chemicals and their detection. 

As the body ages both neurological and motor functions deteriorate. Dr Gary Coulton’s group is studying the changes that occur in the muscle during normal human ageing. Using state-of-the-art proteomic profiling the group have identified different expression profiles in normal slow and fast contracting skeletal muscle, identified biomarkers of subtle heart disease in mutant mice and most recently markers associated with muscle cell senescence in vitro. The results of this work are now being applied to answer questions relating to exercise in health and diseases such as myotonic dystrophy and occular pharyngeal muscular dystrophy.

To complete the life cycle we have two groups interested in neurodegenerative diseases. Prof Brian Austen and his group, Neurodegeneration Unit, are researching the role of protein aggregation in Alzheimer's disease, Parkinson's disease and BRI-related familial dementias.. Mass spectrometry is being used to identify post-translational changes to toxic brain proteins in Alzheimer’s disease brought about by raised cholesterol. The way amyloid aggregates block LTP (a brain memory process), in the hippocampus, is being investigated in collaboration with Royal Holloway, University of London and inhibitors devised to block aggregation are being developed as drugs. The group of Dr Ceri Davies continues the Centres interest in Alzheimer’s disease, which is in addition to his interests in schizophrenia, behavioural neuroscience and comparative neuroanatomy.