The University of Sheffield
Department of Biomedical Science

Project Title: The roles and targeting of membrane microdomains in immune cells

Project supervisors: Professor Ian Sabroe (Faculty of Medicine & CMIAD), Professor Elizabeth Smythe (BMS & CMIAD) and Dr Elizabeth Seward (BMS & CMIAD)

Application deadline: Friday 14 December 2012.

Project description:

Cell membranes are often the points of initiation of cell signalling. Membranes are complex cellular components, with signalling being initiated in highly organised domains of the membranes. These domains, called membrane microdomains or lipid rafts, are dynamic structures that are themselves highly regulated[1].

We are developing new ways of targeting membrane microdomains, with an aim to translate the basic science of membrane function into the development of new treatments. In particular, we have developed data showing that addition of liposomes of specific phospholipids can partition into cellular membranes on the cell surface, the endosome, and golgi apparatus, and disrupt inflammatory signalling[2].

The proposed project will use a variety of techniques to explore the roles of microdomains in cellular function, and explore in more detail how we can target them therapeutically. A range of lipids will be studied, seeking to determine optimal ways of targeting microdomains, and determining which lipids gain access to which cellular compartments, and by which mechanisms. We will determine whether targeting of membrane microdomains by specific reagents modulates functions of innate immune cells and disrupts pro-inflammatory signalling. We will determine if microdomains are also formed in intracellular organelles.

The successful applicant would learn how to make and prepare liposomes, use microscopy to study the trafficking of lipids into cells and their subcellular localisation, use cell biology techniques to study immune cell function, and molecular and cellular techniques to explore the roles of subcellular microdomains.

References:

[1] Lingwood, D. and K. Simons (2010).
"Lipid rafts as a membrane-organizing principle."
Science 327(5961): 46-50.

[2] Parker, L.C., Prestwich, E.C., Ward, J.R., Smythe, E., Berry, A., Triantafilou, M., Triantafilou, K., and Sabroe, I. (2008)
A phosphatidylserine species inhibits a range of TLR, but not IL-1β, induced inflammatory responses by disruption of membrane microdomains.
J. Immunol. 181, 5606–5617.

Contact details:

Professor Elizabeth Smythe

Professor Ian Sabroe

Dr Elizabeth Seward

Further Information:

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