Overview
My research is currently within the Division of Infection and Immunity and is focussed on neutrophil behaviour and signalling at the individual cell level..
I established the Neutrophil Siganlling Group within Cardiff Univesity Medical School with the aim of using novel technques to undestand and influence the activity of these cells which are impratnt in inflammatory disease.
For a number of years, the Neutrophil Signalling lab has studied signalling in living human neutrophils. In this way, the link between the chemical change within the neutrophil and its responses have been observed and the effect of experimental interventions established. This has necessitated the invention of some novel micro-manipulation and imaging techniques. The individual cell approach, however, has revealed an insight into how neutrophils are able to carry out their work-programme in a co-ordinated and effective manner. It also points towards therapeutic targets which may be beneficially manipulated in inflammatory disease.
We have established that an important Ca2+ "read-out" is the Ca2+ activated protease, mu-calpain activation. Since the action of the protease may be long-lived (or irreversible), this would provide a molecular memory of previous Ca2+ signalling within the cell. This has become an important focus for progress towards understanding the link between Ca2+ signals and physiological or pathological responses by the neutrophils.
Research
The neutrophil represents an unusual cell type within the body, in which there is a degree of autonomy of cell-response decision-making. In some respects, the possible response outcomes are "primitive" cell behavioural responses, e.g. cell shape change, phagocytosis and chemotaxis, whereas in other respects there are more sophisticated outcomes, e.g. apoptosis, gene expression and oxidase assembly. Individual neutrophils must perform a program of activity in the correct sequence, location and timing (based on their repertoire of behaviours) to produce effective anti-bacterial protection. Yet, many of the same steps lead to pathological and chronic inflammatory diseases, such as rheumatoid arthritis.
The goal of our research is to understand the signalling and integration of these separate behaviours. While this is a worthy goal in itself, as it contributes to our fundamental knowledge of cellular processes; it underpins the larger aim of understanding and ultimately preventing the aberrant behaviour of these cells during inflammatory diseases. At present, the Group has focused on three aspects of neutrophil signalling (i) cytosolic free Ca2+ signals (ii) PIP2 generation and signalling and (ii) calpain translocation and activation. We have built up the necessary equipment for measurement, manipulation and imaging chemical changes in individual living neutrophils, and solved some of the difficult problems which arise when working with these cells.
Teaching
i) Cell Signalling series of lecturers (3) – BSc (Hons)
(ii) Core course Cell Signalling (3) BSc Intercalated
(iii) Phagocytes, function, signalling and pathology (3) BSc and BSc Intercalated
(iv) Neutrophilopathies
Biography
Professor of Experimental Cell Biology: currently Emeritus Professor (active).
Education
First degree BSc (Pharmacology) University College London (UCL)
PhD Department of Pharmacology, University College London (Ca2+ in mast cell secretion)
FRMS
Honours and awards
The group has received funding from MRC, Wellcome Trust, BBSRC, Arthritis and Research Campaign (ARC), BHF, National Research Network, Cystic Fibrosis Trust and others.
Professional memberships
FRMS Memberships/External Activities
Biochemical Society
British Soc Cell Biology
Academic positions
Professor Emeritus
New Blood Lecturer, Senior Lecturer, Reader and Professor at Cardiff University
Director of Postgraduate Research (MEDIC)
Committees and reviewing
I have served on many committees within the University.
Externally I have served on the
Royal Microscopical Society Comitee (Cell Biology) mermbarer and then Hon Sec
Biochemical Soc (Cell Biology Theme comittee)
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