PhD Research Project

My Shortlist0

This project is no longer listed in the FindAPhD database
and may not be available.

Click here to view other PhD studentship opportunities at University of Sheffield.

Temporal and spatial organization of receptor signaling microdomains by plasma membrane lipids and their synthetic enzymes

Institution:

University of Sheffield

Dept/School/Faculty:

Department of Biomedical Science

PhD Supervisor:

Dr E Seward

Co-Supervisor:

Prof D Strutt

Application Deadline:

Applications accepted all year round

Funding Availability:

Competition Funded PhD Project (European/UK Students Only)

PhD Research Project

Click here to visit the University of Sheffield website

Changes in membrane lipids accompany a range of neurodegenerative diseases including Alzheimer’s and other age-related conditions, it is therefore important to understand how membrane lipids are maintained and organized in health and how these may be manipulated in disease. The aim of this project is to identify the role of PIP5 kinases in the generation of G protein coupled receptor (GPCR) signalling microdomains and their regulation of membrane trafficking. Phosphatidylinositol (4,5)-bisphosphate (PIP2) is a critical constituent of cellular membranes and is a key regulator of a wide variety of cell functions including adhesion, cell polarity, endo- , exo- and phagocytosis. In addition to its second messenger functions, PIP2 is the substrate for two key signalling molecules, namely phospholipase C and phosphatidyl 3-kinase and thus is a major component of receptor signalling. Recent studies indicate that the levels of PIP2 in the membrane are not uniformly distributed, but that there are different ‘pools’ of PIP2 that are temporally and spatially regulated, thereby giving rise to highly localized signalling microdomains. PIP5 kinases are enzymes which catalyze the production of PIP2 and are likely to control the formation of these microdomains. This project will combine the expertise of two supervisors in GPCR signalling to examine the role of PIP5 kinases in regulating localized receptor signalling in vivo in Drosophila (Strutt) and primary mammalian cells (Seward). High resolution live cell fluorescent imaging techniques will be used to track the formation of PIP2 microdomains and their spatial organization relative to receptors in the two experimental systems. The consequences of disrupting isoform specific PIP5K function on the spatial and temporal properties of receptor signalling and function will then be evaluated.

The results of this project will provide much needed new knowledge on the role of membrane lipids in organizing receptor specific functions and insight into how dietary supplements and aging-related changes in plasmalemmal composition affect GPCR function.

Funding Notes:

This research project is one of a number of projects in the department. It is in competition for funding with the other projects. Usually the project which receives the best applicant will be awarded the funding. The funding is available to citizens of a number of European countries (including the UK). In most cases this will include all EU nationals. However full funding may not be available to all applicants.