Primary Supervisor: Dr Sarah L Horswell, School of Chemistry

Secondary supervisor: Dr Liam R. Cox

PhD project title: Understanding the interactions between glycosylceramides, saposins and the cell membrane

University of Registration: University of Birmingham

Project outline:

The human immune system is capable of responding to a wide range of molecular stimuli, to produce a specific immune response. Whilst much of the immunology literature has focused on the role of peptide antigens in generating an immune response, a set of T cells known as invariant natural killer T-cells (iNKT) are activated by a very different class of molecules, namely lipids. The purpose of this project is to ascertain how these lipids interact with other components of the biological cell membrane. A range of physical techniques, such as atomic force microscopy, neutron and x-ray reflectivity and vibrational spectroscopy, will be employed to understand the organisation of the lipid molecules, how this may influence their properties and function, and how they are affected by the incorporation of the biologically active lipids. Further, the interactions of saposins with the functional lipids and their extraction from membrane models will be studied at a molecular level. The project is multidisciplinary and will involve a range of physical measurements of model membrane systems and collaboration with synthesis groups. The interaction of the lipids with proteins involved in the immune response will also be studied. The results from the project will enable us to answer some important questions about how the structure of the molecules determines their effect on the immune response.

BBSRC Strategic Research Priority: Understanding the Rules of Life: Structural Biology

Techniques that will be undertaken during the project:

• Surface pressure-area isotherm measurements and monolayer transfer
• Capacitance and impedance measurements
• Vibrational spectroscopy
• Atomic force microscopy
• Neutron and X-ray Reflectometry, Grazing Incidence X-ray Diffraction
• Collaboration with synthesis groups

Contact: Dr Sarah Horswell, University of Birmingham