Intracellular signalling pathways between nociceptin (N/OFQ) and the NOP receptor in immune cells during sepsis

Nociceptin is an endogenous peptide which has a role in experimental models of sepsis/inflammation. The extent to which NOP is upregulated, and how this differs in response to septic or non-septic forms of inflammation, is unclear. This project will address the following:
Hypothesis 1: The nociceptin system is upregulated by inflammatory stimuli to increase leucocyte production of N/OFQ. This involves monocytes, leucocytes and granulocytes but the relative importance and contribution of these cell types varies.

Hypothesis 2: There will be differential immune cell type signalling cascades for NOP activation in terms of GTPgamma35S binding and cAMP turnover.

Hypothesis 3: N/OFQ release modulates immune responses to sepsis by effects on Toll like receptor (TLR-4, -2 & 5) and other signalling pathways.

The project will allow the student to join a group of clinicians and scientists with recognised expertise in this field. The project will use both laboratory and clinical models of sepsis. Our established techniques include qPCR, cell transfection and tissue culture, immunofluorescence techniques, immune cell migration and intracellular signalling pathways. The projects also involves the opportunity to further develop and refine our sandwich ELISA assays for N/OFQ and NOP, with ample facilities for training and support.

For informal discussions and further information please contact:
Dr Jonathan Thompson,
Senior Lecturer/Hon. Consultant in Anaesthesia & Critical Care
Tel 0116 258 5291
Email: [Email Address Removed]


We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.