Call Lab

With collaborator Sarel Fleishman (Weizmann Institute of Science, Israel), we have developed and validated a panel of de novo designed transmembrane domains (TMDs) that form stable and specific monomeric, dimeric, trimeric and tetrameric structures in cell membranes. We used these to enforce the corresponding oligomeric states in second-generation chimeric antigen receptors (CARs) against the solid tumour antigen HER2 and showed that both tumour control and cytokine production scaled in direct proportion to the designed oligomeric structure of the TMD (see eLife 2022).

Ongoing work in this program is focused on (1) expanding our panel of available TMD sequences and structures, (2) testing the clinical relevance of these new tools for optimising the safety/efficacy profiles of cellular immunotherapies in specific cancer contexts and (3) developing even more sophisticated applications for these sequences in the cellular immunotherapy space.

Project resources:
‘Goldilocks’ treatment window could lead to cancer therapy without harmful side-effects 

Team members:
Melissa Call, Laboratory Head, BSc MSc PhD Auckland
Ashleigh Davey, Senior Postdoctoral Fellow, BBiotech(Hons) Monash PhD Melbourne
Colin Hockings, Senior Postdoctoral Fellow, BA(Hons) Cambridge PhD Melbourne
Emma Petley, Postdoctoral Fellow, BBiomedSci MBiomedSci Wellington, PhD Melbourne
Samyuktha Ramesh, Postdoctoral Fellow, BTech Anna Univ Chennai PhD Melbourne
Lincoln Smith, Research Assistant, BBiotech(Hons) PhD Newcastle
Julie Nguyen, Research Assistant, BSc(Hons) Monash
Corinna Clemens, Masters Student, BBiotech Aachen
Mengzhen Chen, Masters Student, BSc Melbourne

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 utilizes deep mutational scanning methods coupled to next-generation sequencing to evaluate how a large number of mutations in these receptors’ TM and flanking regions affects their function.

Project resources:
Genetic cause of blood disease found

Team members:
Melissa Call, Laboratory Head, BSc MSc PhD Auckland
Samyuktha Ramesh, Postdoctoral Fellow, BTech Anna Univ Chennai PhD Melbourne
Margareta Go, Research Assistant, BMedSci Univ Applied Sciences Utrech
Lincoln Smith, Research Assistant, BBiotech(Hons) PhD Newcastle