Cytokines Receptors and Signal Transduction
Multi-functional cytokines and haemopoietin receptors.
Cytokines are secreted proteins that allow cells to communicate with one another. Cytokines act by binding to multi-subunit receptors expressed on the surface of responsive cells and activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) pathway. While some cytokines, such as G-CSF and TPO affect a single lineage of blood cells; others, like leukaemia inhibitory factor (LIF) have diverse effects. For example, while we purified LIF on the basis of its ability to induce the macrophage differentiation of blood cells, we also found that it could inhibit the differentiation of embryonic stem (ES) cells, leading to its sale as ESGRO and use in laboratories throughout the world. We have also identified a number of cytokine receptors including the interleukin-11 receptor and a shared component of the interleukin-4 and interleukin-13 receptors. In collaboration with Zenyth Therapeutics we produced a panel of antagonistic human antibodies to the human IL-13 receptor, which are currently being developed as a treatment for asthma in conjunction with Merck. Using a similar strategy we are also collaborating with Professor Ian Wicks to determine whether inhibitors of G-CSF action have a place in the treatment of inflammatory diseases such as arthritis. This project is being commercialised by Zenyth Therapeutics and Murigen Therapeutics.