Understanding the mechanism of type I cytokine receptor activation

Understanding the mechanism of type I cytokine receptor activation

Project details

Homodimeric type I cytokine receptors for growth hormone, erythropoietin and thrombopoietin (GHR, EpoR, TpoR) control processes essential to human health such as tissue growth, regeneration and blood cell production. Impaired activation and/or signalling of these receptors can lead to various pathological conditions, including blood pathologies, cancers, developmental and metabolic disorders. 

GHR, EpoR, TpoR transmit signals by forming specific structures in their transmembrane domains (TM), though the identities of active and inactive orientations are not well understood. Our laboratory utilises deep mutational scanning method coupled to next-generation sequencing to evaluate how mutating a large number of residues in receptors’ TM affects their function. 

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

The Call lab is co-directed by Matthew and Melissa Call and focuses on understanding the basic mechanisms and effects of transmembrane (TM) interactions by cell-surface immune receptors. 

Our research group (2 post-docs, 3 PhD students and 2 research assistants) utilises knowledge from structural studies and mutational analysis of novel and conventional TM domains to examine functional consequences of transmembrane interactions in both cell culture assays and in vivo mouse models. 

Projects within the laboratory span across multiple disciplines including structural biology, molecular biology and immunology, and members of the lab receive strong training in one or more of these research areas. 

 

Email supervisors

 

Researchers:

Dr Melissa Call

Dr Melissa Call in a laboratory
Dr
Melissa
Call
Laboratory Head
Dr Anna Malinovitch
Dr
Anna
Malinovitch
Structural Biology division

Project Type: