Determining the mechanism of type I cytokine receptor triggering

Determining the mechanism of type I cytokine receptor triggering

Project details

Homodimeric type I cytokine receptors for factors like erythropoietin and thrombopoietin control blood cell production and are commonly mutated in myeloproliferative disorders. They are believed to transmit signals by forming specific structures in their membrane-spanning domains, though the identities of active and inactive orientations are not well understood.

Mutagenesis provides information about regions critical to a protein’s function, but traditional site-directed techniques test relatively few variants and miss a great deal of potentially useful information. We are employing deep mutational scanning to evaluate many variants within a region of interest and measure effects on function using next-generation sequencing of functionally selected cell populations. A student involved in this project will establish random-variant libraries and apply cell culture and cutting-edge sequencing techniques to interrogate receptor activation.

About our research group

Research in the Call lab is co-directed by Matthew and Melissa Call and focuses on understanding the basic mechanisms of transmembrane signaling by cell-surface receptors in immunity and haematopoietic development. We apply a broad range of biochemical, biophysical (X-ray crystallography, solution NMR) and cell-biological techniques to study receptor structure, function and regulation from the atomic scale to in vivo settings. Our interests thus combine the fields of membrane protein structural biology and molecular immunology, and members of the lab receive strong training in either or both of these areas.


Dr Melissa Call

Dr Melissa Call in a laboratory
Laboratory Head

Project Type: