I completed my PhD in Immmunology at Harvard Medical School and the Dana-Farber Cancer Institute (Boston, MA, USA) and completed postdoctoral training in solution NMR of membrane proteins at Harvard Medical School. I then established an independent research program at WEHI in Melbourne in 2010. My lab has a particular focus on how the membrane-embedded portions of receptors (transmembrane domains) contribute to the structure and function of immune-signalling complexes and other important cellular receptors. These are not mere anchors for extracellular and intracellular domains, but in fact they provide a unique platform for molecular interactions and represent the only direct physical link between ligand-binding and signalling domains across the cell barrier.

We combine biochemical and biophysical methods (both X-ray crystallography and solution NMR) with protein engineering, saturating mutagenesis and cellular and molecular immunology techniques to study the mechanics of receptor activation and the regulation of cell-surface proteins in the immune system. A major focus in recent years has been the development (with computational protein design collaborators) and structural characterisation of synthetic transmembrane domains as tools to control the structures and activities of engineered receptors such as chimeric antigen receptors (CARs) for cellular immunotherapies.


Selected publications from Prof Matt Call

Ramesh S, Park S, Im W, Call MJ#, Call ME#. T cell and B cell antigen receptors share a conserved core transmembrane structure. PNAS 2022. 119(48):e2208058119. doi: 10.1073/pnas.2208058119. PMID: 36409917.

Elazar A*, Chandler NJ*, Davey AS*, Weinstein JV, Nguyen JV, Trenker R, Cross, RS, Jenkins MR, Call MJ#, Call ME#, Fleishman SJ#. De novo designed transmembrane domains tune engineered receptor functions. eLife 2022. 11:e75660, PMID: 35506657

Trenker R, Wu X, Nguyen JV, Wilcox S, Rubin AF, Call ME# & Call MJ#. Human and viral membrane-associated E3 ubiquitin ligases MARCH1 and MIR2 recognize different features of CD86 to downregulate surface expression. J Biol Chem 2021. 297:100900, PMID: 34157285.

Bridgford J, Lee SM, Lee CMM, Guglielmelli P, Rumi E, Pietra D, Wilcox S, Chhabra Y, Rubin AF, Cazzola M, Vannucchi AM, Brooks AJ, Call ME# & Call MJ#. Novel Drivers and Modifiers of MPL-dependent Oncogenic Transformation Identified by Deep Mutational Scanning. Blood 2020. 135:287-289, PMID: 31697803

Tan C, Byrne EFX, Ah-Cann C, Call MJ#, Call ME#. A serine in the first transmembrane domain of the human E3 ubiquitin ligase MARCH9 is critical for down-regulation of its protein substrates. J Biol Chem 2019. 294, 2470-2485, PMID: 30554144

Krshnan L, Park S, Im W, Call MJ, Call ME. A conserved αβ transmembrane interface forms the core of a compact T-cell receptor-CD3 structure within the membrane. Proceedings of the National Academy of Sciences, USA 2016. 113, E6649-E6658 PMID: 27791034

Trenker R, Call ME, Call MJ. Crystal Structure of the Glycophorin A Transmembrane Dimer in Lipidic Cubic Phase. Journal of the American Chemical Society 2015. 137, 15676-15679 PMID: 26642914

Knoblich K, Park S, Lutfi M, van ‘t Hag L, Conn CE, Seabrook SA, Newman J, Czabotar PE, Im W, Call ME, Call MJ. Transmembrane Complexes of DAP12 Crystallized in Lipid Membranes Provide Insights into Control of Oligomerization in Immunoreceptor Assembly. Cell Reports 2015. 11,1184-1192 PMID: 25981043

Call ME, Wucherpfennig KW & Chou JJ. The structural basis for intramembrane assembly of an activating immunoreceptor complex. Nature Immunology 2010. 11, 1023-1029 PMID: 20890284

Call ME, Schnell JR, Xu C, Lutz RA, Chou JJ & Wucherpfennig KW. The structure of the zetazeta transmembrane dimer reveals features essential for its assembly with the T cell receptor. Cell 2006. 127, 355-368 PMID: 17055436

Call ME, Pyrdol J, Wiedmann M & Wucherpfennig KW. The organizing principle in the formation of the T cell receptor-CD3 complex. Cell 2002. 111, 967-979 PMID: 12507424

Lab research projects

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