We are dedicated to understanding receptor-transducer coupling where there is a biological imperative that underlies the role of a GPCR in metabolism and the gut-brain axis.
The gut-brain axis refers to the complex two-way communication that occurs between our gastrointestinal tract and our brain. This communication takes the form of hormones that are secreted from the gut and report on feelings of hunger, fullness, the types of nutrients arriving and the types of microbes living in our gut. These hormones may reach the brain directly or signal via the nervous system. Our brain (mainly unconsciously) senses these signals and responds to them in various ways including by communicating (mainly via nerves) back to our gut. Much of this signalling occurs via a special family of sensors called G protein-coupled receptors.
These sensors are on the outside of various different types of cells and communicate the signals into cells where these are converted (by transducers) to changes in cellular behaviour. In some pathological conditions this signalling goes wrong and in others changing this signalling might be a way to treat the disease. We are interested in discovering the reasons why this signalling goes wrong in some diseases and how we might change this signalling to treat other diseases.
How can one receptor couple with different efficiencies to the same transducer?
What allows one receptor to couple to more than one transducer?
How does the membrane environment alter transducer coupling?
How does one receptor alter the coupling of another?
We specialize in a wide variety of biophysical and chemical biology approaches to answer questions of receptor-transducer coupling. These are integrated into whole animal physiology through our collaborative team
Intra- and inter-molecular resonance energy transfer techniques
Orthogonal protein labelling & single molecule studies
High resolution native PAGE
Cell based receptor-transducer coupling assays
We collaborate with the Monash Institute of Pharmaceutical Sciences on structural studies of GPCRs, The Florey Institute of Neuroscience and Mental Health on the role of interactions of ghrelin & dopamine receptors on defecation control, Monash School of Chemistry on novel solvatochromatic fluorophores for protein dynamics studies, the Mayo Clinic on pathophysiological signalling of the cholecystokinin receptor and Austin Health on the role of the calcitonin receptor in programmed cell death & cancer.
We are funded by the School of Biomedical Sciences, the Australian Research Council and the NHMRC.