Centre for Innate Immunity & Infectious Disease

Cytokine signalling laboratory

Laboratory Head: Associate Professor Brendan Jenkins

Cytokine signalling laboratory

The interleukin-6 cytokine family plays an important role in maintaining homeostasis of various biological systems, including pulmonary function, the gastrointestinal tract, haemopoietic (blood) compartment, immune/inflammatory responses and bone metabolism. All members of the interleukin-6 cytokine family use a cell surface receptor molecule called gp130 to transmit intracellular signals controlling cellular functions such as proliferation, differentiation, maturation, and survival.

One of the multiple signalling pathways activated downstream of gp130 activates is the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway, involving the latent transcription factors STAT1 and 3. The importance of mechanisms to properly regulate the activation of these cytokine signalling pathways is evidenced by the fact that over-activation of these STATs is implicated in many human cancers, (eg stomach cancer, liver cancer, prostate cancer, colon cancer), inflammatory diseases (eg arthritis, inflammatory bowel disease) and blood disorders.

However, it remains unclear which gp130-dependent signalling pathways are required for the physiological actions of this cytokine family during homeostasis. To address this, Associate Professor Jenkins’ team is using in vivo models in which specific mutations in gp130 disrupt the normal activation of certain gp130-dependent signalling pathways. Using this approach, they have demonstrated the broad pathological consequences of uncontrolled gp130-dependent signal transduction from this cytokine family, resulting in blood disorders, chronic inflammatory responses, lung disease and stomach cancer.

The projects undertaken in this group encompass numerous molecular biological and genetic approaches to better understand the mechanisms by which uncontrolled signal transduction from this cytokine family leads to these disease states. This research will ultimately assist in identifying genes which can potentially be used as biomarkers for screening/early detection of specific diseases, and also targets for the design of therapeutic treatment strategies.