Members of the Department of Pharmacology investigate signalling mechanisms that communicate the extracellular environment to the cell, and these are subsequently integrated into functional ‘decisions’. Earlier ground breaking studies from Pharmacology group leaders and colleagues established Ca2+signalling as essential for cell function; this research focus has informed much of current investigation. An overall aim of research in Pharmacology is to identify potential drug targets, which can subsequently be employed to develop strategic therapeutic targets.
Together with Mike Berridge, members of Pharmacology (Irvine) helped to establish inositol 1,4,5-trisphosphate as a second messenger regulating calcium mobilisation. Current focus is on the small family of phosphatidylinositol 5-phosphate 4-kinases, introducing genomic tagging as a technique to give new insights into their cellular targeting and functions.
Many pathways interact with Ca2+ flux to integrate signalling. Amongst these organisation of adenylyl cyclases in cells and their role as signalling scaffolds is important. Targeted sensors for both cyclic AMP and Ca2+ are employed to study the dynamics and influences upon these messengers (Cooper).
Academics specializing in this area
Mechanisms and roles of transport proteins at the blood-brain barrier, in red blood cells and in malarial parasites
The ATP Binding Cassette superfamily of proteins contains several members that act as transporters, so providing protection to cells and tissues against cytotoxic stresses. Past work by our groups has examined the mechanisms by which these transporters bring about transport of various different substrates, identifying the particular proteins involved, looking at their specific locations at the blood-brain barrier and factors regulating their expression under normal and pathological conditions. Regulatory factors include the influences of pH, hypoxic and oxidative challenge and signalling from other brain cell types. In a separate series of studies the functions of these transporters in red blood cells and in malarial parasites in the erythrocyte stages of their life cycle have been investigated. Other transporters of interest have been those regulating the ionic content of both endothelial cells at the blood-brain barrier and of malaria parasites. Determining if any of these transporters make good targets for therapeutic intervention has been a major aim and, in the context of erythrocyte stage malarial parasites, this work continues in collaboration with the group of Prof. Kiaran Kirk at ANU, Canberra, Australia. The current hypothesis is that one of the ABC transporters is the glutathione conjugate transporter that must exist in the parasite membrane.
Techniques that were employed in the above work included: tissue isolation; primary cell culture; molecular biological methods for modifying gene expression and for manipulating and analysing RNA, DNA and proteins; immunocytochemistry; transport studies with radiolabelled and with fluorescent tracers; visualising and quantifying intracellular distribution of fluorescent substrates, analysing intracellular pH and measuring ion channel activity using intracellular recordings.
Enquiries about any of our work current or past are welcome.
Academics specializing in this area
Diseases of the circulation (hypertension, heart failure, coronary vascular disease and stroke) are some of the biggest killers in Western society. We aim to improve understanding of the effects of disease on blood vessel function and to produce strategies for prevention and alleviation of organ damage arising from blood vessel malfunction. We are approaching this problem by elucidating the physiological, cellular and molecular mechanisms of drug action on the vasculature and its endothelial lining...