2006 Strategic StudentshipsEstrogen/IGF cell signalling in blood vessels of the humanmaternal/fetal interface

The School of Medicine is offering fully-funded* 3 year PhDstudentships, to commence in 2006, across a wide variety of researchareas.Applications are invited from EU/UK* students who have, or expect toachieve, a 1st Class or 2:1 honours degree in a relevant subject.

Details of the projects available are given below.

For any further information on specific projects please contact theproject supervisor.

These studentships are highly competitive and applicants are thereforeencouraged to apply as soon as possible

*Overseas students of high academic achievement and outstandingresearch potential may be eligible for part-funding.

Such students should contact the project supervisor(s) for advicebefore making a formal application.

THE FOLLOWING PROJECTS ARE AVAILABLE WITHIN THE DIVISION OF HUMAN DEVELOPMENT

Estrogen / IGF cell signalling in blood vessels of the humanmaternal/fetal interface

Supervisors: Dr Melissa Westwood/ Dr Mike Taggart

Normal fetal growth depends on maternal / fetal exchange of nutrients,oxygen and waste products and therefore adequate remodelling of theuterine and placental vasculature is an important feature ofuteroplacental perfusion and pregnancy success. This suggests that, inthese circulatory systems, blood flow is regulated by factors withinthe local environment; this is especially true of placentalvasculature that is lacking in autonomic innervation.

Estrogen is known to cause vessel relaxation and recent studies havesuggested that instead of activating the receptors (ERa and ERb) inthe nucleus, it may mediate vasodilation via activation of plasmamembranous ERa and ERb; this activates intracellular signallingmolecules, e.g. PI-3 kinase / Akt and MAP kinase, more typicallyassociated with growth factor signalling. One such growth factor isinsulin-like growth factor-I (IGF-I). IGF-I is also essential fornormal fetal growth and whilst it is a recognised vasodilator of othervascular beds, surprisingly little is known about its ability toregulate the reactivity of vessels at the maternal / fetal interface.

The first aim of this studentship will be to use myography andplacental perfusion to characterise the effect of IGF-I and/orestrogen on vessels from the maternal / fetal interface. As it islikely that vasodilatory actions are mediated by endothelial cells, wewill, secondly, investigate the signalling pathways activated byestrogen and IGF-I in isolated endothelial cells. Thirdly, we willdetermine the nature of any cross-talk between these pathways. Recentwork based on other cell systems has suggested that integration ofsignals from estrogen and IGF-I depends on receptor co-localisationwithin specialised regions of plasma membrane - termed caveolae - andtheir consequent interaction with the resident caveolin proteins.Thus, the final part of this project will use techniques for gene andprotein knock-out / knock-down to investigate if modulation ofcaveolin _expression alters IGF-I / estrogenic signalling and functionin endothelial cells.

This study will provide novel information on the mechanisms enablingcross-talk between steroid- and growth factor-activated signallingpathways and may ultimately lead to an innovative approach fortargeting abnormal vascular function in problem pregnancies.

For further details contact: melissa.westwood@manchester.ac.uk

http://www.medicine.manchester.ac.uk/graduate/studentships/