Structural Biology

Group Head: Dr Mika Jormakka

The Structural Biology Group is currently focusing on structural studies of membrane proteins involved in cellular respiration, cell signalling and transport. Of particular interest is transporters involved in cellular drug extrusion - these are proteins 'pumping' drugs out from the cell - and therefore reduce the efficiency of, for example, cancer chemotherapy and antibiotics. We hope to increase our understanding of these processes by obtaining structural information of these multi-drug transporters, to pave the way for therapeutic design.

Research focus

The recently established structural biology program at Centenary Institute is focused on elucidating 3D structures of membrane proteins involved in fundamental cellular processes by x-ray crystallography. Membrane proteins constitute roughly a third of the genes in genomes and perform a plethora of essential cellular functions. Their importance is reflected in that they represent 50-70 per cent of all pharmacological therapeutic targets. Structural biology, and the use of X-ray crystallography, provides a precise and detailed model of how a protein is folded in space. This enables us to understand the mechanism by which a protein function, and also provide a route to structure based drug discovery. Of particular interest to this laboratory are structural studies of membrane proteins relevant to human disease and disorders, such as drug extrusion and respiratory disorders.   

Membrane transporters are involved in cellular influx and efflux of nutrients, ions and drugs. As such, they fill an essential niche in cellular homeostasis and are, in many cases, implicated in bacterial virulence, as well as drug extrusion, with important implications for cancer and anti-microbial drug resistance. Our studies are focused on multi-drug transporters belonging to the novel ‘multi-drug and toxin extrusion’ (MATE) family. 

Signal transduction at the cellular level refers to the movement of signals from outside the cell to inside. Many disease processes such as diabetes, heart disease, autoimmunity and cancer arise from defects in signal transduction pathways, further highlighting the critical importance of signal transduction to biology as well as medicine. Central in human signal transduction is G-protein coupled receptors (GPCR). These are receptors localised in the membrane, sensing external stimuli, which is then translated to a cellular response. Of particular interest in our group are receptors involved in regulation of glucose levels in our blood system and their potential as targets for therapeutic drug design.

Please also visit the Australian Membrane Protein Structure Initiative.