A/Prof Melissa Call, Lab Head | WEHI Researcher Profile

About

We have a particular focus on how the transmembrane domains of receptors contribute to the structure and function of immune-signalling complexes. These are not mere anchors for extracellular and intracellular domains, but provide a unique platform for molecular interactions and represent the only direct physical link between ligand-binding and signalling domains across the cell barrier.

To understand how receptors are activated and the interactions the make with other proteins we are using deep-mutational scanning to uncover mechanistic insights, such as which areas of the protein are susceptible to disease-causing mutations and how to these relate to the natural function of the receptor. A major focus in recent years has been the development (with computational protein design collaborators) and structural characterisation (by x-ray crystallography) of synthetic transmembrane domains as tools to control the structures and activities of engineered receptors such as chimeric antigen receptors for CAR T-cell immunotherapies.

During the pandemic we pivoted some of our research towards understanding how SARS-CoV-2 will respond to therapeutics targeting the viral proteases required for SARS-CoV-2 replication. Our research will predict viral escape mutants before they are observed in the clinic and provide deeper mechanistic insight into Mpro and PLpro function.

Education

Grants and funding

Publications

Selected publications from A/Prof Melissa Call

Cater RJ, Ryan RM, Oakhill JS, Czabotar P, Murphy JM, Call MJ. Structure, function, surf, repeat: A week at Lorne Proteins 2024. Structure. 2024;32(11):10.1016/j.str.2024.10.007

Wu X, Go M, Nguyen JV, Kuchel NW, Lu BGC, Zeglinski K, Lowes KN, Calleja DJ, Mitchell JP, Lessene G, Komander D, Call ME, Call MJ. Mutational profiling of SARS-CoV-2 papain-like protease reveals requirements for function, structure, and drug escape. Nature Communications. 2024;15(1):10.1038/s41467-024-50566-9

Ramesh S, Go M, Call ME, Call MJ. Deep mutational scanning reveals transmembrane features governing surface expression of the B cell antigen receptor. Frontiers in Immunology. 2024;15:10.3389/fimmu.2024.1426795

Borger JG, Ng AP, Anderton H, Ashdown GW, Auld M, Blewitt ME, Brown DV, Call MJ, Collins P, Freytag S, Harrison LC, Hesping E, Hoysted J, Johnston A, McInneny A, Tang P, Whitehead L, Jex A, Naik SH. Artificial intelligence takes center stage: exploring the capabilities and implications of ChatGPT and other AI‐assisted technologies in scientific research and education. Immunology and Cell Biology. 2023;101(10):10.1111/imcb.12689

Chandler NJ, Davey AS, Elazar A, Weinstein JY, Nguyen JV, Trenker R, Cross RS, Jenkins MR, Call ME, Fleishman SJ, Call MJ. De novo -designed transmembrane domains tune chimeric antigen receptor function. Acta Crystallographica Section A: Foundations and advances. 2023;79(a2):10.1107/s2053273323086722

Abbott RC, Iliopoulos M, Watson KA, Arcucci V, Go M, Hughes‐Parry HE, Smith P, Call MJ, Cross RS, Jenkins MR. Human EGFRvIII chimeric antigen receptor T cells demonstrate favorable safety profile and curative responses in orthotopic glioblastoma. Clinical & Translational Immunology. 2023;12(3):10.1002/cti2.1440

Ramesh S, Park S, Im W, Call MJ, Call ME. T cell and B cell antigen receptors share a conserved core transmembrane structure. Proceedings of the National Academy of Sciences of the United States of America. 2022;119(48):10.1073/pnas.2208058119

Elazar A, Chandler NJ, Davey AS, Weinstein JY, 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;11:10.7554/elife.75660

Calleja DJ, Kuchel N, Lu BGC, Birkinshaw RW, Klemm T, Doerflinger M, Cooney JP, Mackiewicz L, Au AE, Yap YQ, Blackmore TR, Katneni K, Crighton E, Newman J, Jarman KE, Call MJ, Lechtenberg BC, Czabotar PE, Pellegrini M, Charman SA, Lowes KN, Mitchell JP, Nachbur U, Lessene G, Komander D. Insights Into Drug Repurposing, as Well as Specificity and Compound Properties of Piperidine-Based SARS-CoV-2 PLpro Inhibitors. Frontiers in Chemistry. 2022;10:10.3389/fchem.2022.861209

Call MJ, Davey AS. Hello Possums!. Immunology and Cell Biology. 2021;99(7):10.1111/imcb.12483