2006 Strategic Studentships
Estrogen/IGF cell signalling in blood vessels of the human maternal/fetal interface
Faculty Of Medical And Human Sciences
School Of Medicine
Division Of Human Development
The School of Medicine is offering fully-funded* 3 year PhD studentships, to commence in 2006, across a wide variety of research areas.
Applications are invited from EU/UK* students who have, or expect to achieve, 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 the project supervisor.
These studentships are highly competitive and applicants are therefore encouraged to apply as soon as possible
*Overseas students of high academic achievement and outstanding research potential may be eligible for part-funding.
Such students should contact the project supervisor(s) for advice before making a formal application.
THE FOLLOWING PROJECTS ARE AVAILABLE WITHIN THE DIVISION OF HUMAN DEVELOPMENT
Estrogen / IGF cell signalling in blood vessels of the human maternal/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 the uterine and placental vasculature is an important feature of uteroplacental perfusion and pregnancy success. This suggests that, in
these circulatory systems, blood flow is regulated by factors within the local environment; this is especially true of placental vasculature that is lacking in autonomic innervation.
Estrogen is known to cause vessel relaxation and recent studies have suggested that instead of activating the receptors (ERa and ERb) in the nucleus, it may mediate vasodilation via activation of plasma membranous ERa and ERb; this activates intracellular signalling molecules, e.g. PI-3 kinase / Akt and MAP kinase, more typically associated with growth factor signalling. One such growth factor is insulin-like growth factor-I (IGF-I). IGF-I is also essential for
normal fetal growth and whilst it is a recognised vasodilator of other vascular beds, surprisingly little is known about its ability to regulate the reactivity of vessels at the maternal / fetal interface.
The first aim of this studentship will be to use myography and placental perfusion to characterise the effect of IGF-I and/or estrogen on vessels from the maternal / fetal interface. As it is likely that vasodilatory actions are mediated by endothelial cells, we will, secondly, investigate the signalling pathways activated by estrogen and IGF-I in isolated endothelial cells. Thirdly, we will determine the nature of any cross-talk between these pathways. Recent work based on other cell systems has suggested that integration of signals from estrogen and IGF-I depends on receptor co-localisation within specialised regions of plasma membrane - termed caveolae - and their consequent interaction with the resident caveolin proteins.
Thus, the final part of this project will use techniques for gene and protein knock-out / knock-down to investigate if modulation of caveolin expression alters IGF-I / estrogenic signalling and function in endothelial cells.
This study will provide novel information on the mechanisms enabling cross-talk between steroid- and growth factor-activated signalling pathways and may ultimately lead to an innovative approach for targeting abnormal vascular function in problem pregnancies.
For further details contact: melissa.westwood@manchester.ac.uk
http://www.medicine.manchester.ac.uk/graduate/studentships/
Click here for Employer Profile
Estrogen/IGF cell signalling in blood vessels of the human maternal/fetal interface
Faculty Of Medical And Human Sciences
School Of Medicine
Division Of Human Development
The School of Medicine is offering fully-funded* 3 year PhD studentships, to commence in 2006, across a wide variety of research areas.
Applications are invited from EU/UK* students who have, or expect to achieve, 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 the project supervisor.
These studentships are highly competitive and applicants are therefore encouraged to apply as soon as possible
*Overseas students of high academic achievement and outstanding research potential may be eligible for part-funding.
Such students should contact the project supervisor(s) for advice before making a formal application.
THE FOLLOWING PROJECTS ARE AVAILABLE WITHIN THE DIVISION OF HUMAN DEVELOPMENT
Estrogen / IGF cell signalling in blood vessels of the human maternal/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 the uterine and placental vasculature is an important feature of uteroplacental perfusion and pregnancy success. This suggests that, in
these circulatory systems, blood flow is regulated by factors within the local environment; this is especially true of placental vasculature that is lacking in autonomic innervation.
Estrogen is known to cause vessel relaxation and recent studies have suggested that instead of activating the receptors (ERa and ERb) in the nucleus, it may mediate vasodilation via activation of plasma membranous ERa and ERb; this activates intracellular signalling molecules, e.g. PI-3 kinase / Akt and MAP kinase, more typically associated with growth factor signalling. One such growth factor is insulin-like growth factor-I (IGF-I). IGF-I is also essential for
normal fetal growth and whilst it is a recognised vasodilator of other vascular beds, surprisingly little is known about its ability to regulate the reactivity of vessels at the maternal / fetal interface.
The first aim of this studentship will be to use myography and placental perfusion to characterise the effect of IGF-I and/or estrogen on vessels from the maternal / fetal interface. As it is likely that vasodilatory actions are mediated by endothelial cells, we will, secondly, investigate the signalling pathways activated by estrogen and IGF-I in isolated endothelial cells. Thirdly, we will determine the nature of any cross-talk between these pathways. Recent work based on other cell systems has suggested that integration of signals from estrogen and IGF-I depends on receptor co-localisation within specialised regions of plasma membrane - termed caveolae - and their consequent interaction with the resident caveolin proteins.
Thus, the final part of this project will use techniques for gene and protein knock-out / knock-down to investigate if modulation of caveolin expression alters IGF-I / estrogenic signalling and function in endothelial cells.
This study will provide novel information on the mechanisms enabling cross-talk between steroid- and growth factor-activated signalling pathways and may ultimately lead to an innovative approach for targeting abnormal vascular function in problem pregnancies.
For further details contact: melissa.westwood@manchester.ac.uk
http://www.medicine.manchester.ac.uk/graduate/studentships/
Click here for Employer Profile