The Walter and Eliza Hall Institute of Medical Research

Dr Melissa Call

Details

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Division: Structural Biology

Research Overview

Our joint research group has a long-standing interest in how molecular encounters outside the cell are translated into intracellular biochemical signals that direct immune responses. The now-classic example of peptide:MHC complexes binding to the T cell antigen receptor (TCR) to activate T cells has been a major focus in previous work.

While the structural determinants of MHC/TCR binding, and the construction of the TCR complex are becoming better understood, the mechanism by which receptor engagement outside the cell is sensed by signalling molecules inside the cell is still an open question. The new challenge is to understand the forces and motions linking the receptor-ligand encounter to the initiation of an intracellular biochemical signal through receptors for antigens, chemokines and other molecular cues.

We have a particular focus on how the structure and dynamics of membrane-embedded receptor domains contribute to the function of immune-signalling complexes. These portions of proteins are not mere anchors for soluble domains, but in fact provide a unique platform for protein function. They also represent the only direct physical link between ligand-binding and signalling domains across the cellular membrane.

Our lab combines biochemical and biophysical methods (both X-ray crystallography and solution NMR) with expertise in cellular and molecular immunology to study the mechanics of transmembrane signalling in the immune system. We aim to understand both how ligand binding is mechanically communicated across the lipid bilayer and how the unique physical and chemical characteristics of the membrane environment contribute to and regulate these functions.

Research Interests

Honours or PhD project available for February 2012 entry: Mechanics of transmembrane signalling in the immune system.

Selected Publications

1. Call MJ. Small molecule modulators of MHC class II antigen presentation: Mechanistic insights and implications for therapeutic application. Mol Immunol. 2011 Jun 13. PMID: 21676462
2. Wucherpfennig KW, Gagnon E, Call MJ, Huseby ES, Call ME. Structural biology of the T-cell receptor: insights into receptor assembly, ligand recognition, and initiation of signaling. Cold Spring Harb Perspect Biol. 2010 Apr 1;2(4):a005140 PMID: 20452950
3. Wucherpfennig KW, Call MJ, Deng L, Mariuzza R. Structural alterations in peptide-MHC recognition by self-reactive T cell receptors. Curr Opin Immunol. 2009 Dec;21(6):590-5. PMID: 19699075
4. Call MJ, Xing X, Cuny GD, Seth NP, Altmann DM, Fugger L, Krogsgaard M, Stein RL, Wucherpfennig KW. In vivo enhancement of peptide display by MHC class II molecules with small molecule catalysts of peptide exchange. J Immunol. 2009 May 15;182(10):6342-52. PMID: 19414787
5. Grotenbreg GM, Nicholson MJ, Fowler KD, Wilbuer K, Octavio L, Yang M, Chakraborty AK, Ploegh HL, Wucherpfennig KW. Empty class II major histocompatibility complex created by peptide photolysis establishes the role of DM in peptide association. J Biol Chem. 2007 Jul 20;282(29):21425-36. PMID: 17525157
6. Moza B, Varma AK, Buonpane RA, Zhu P, Herfst CA, Nicholson MJ, Wilbuer AK, Seth NP, Wucherpfennig KW, McCormick JK, Kranz DM, Sundberg EJ. Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1. EMBO J. 2007 Feb 21;26(4):1187-97. PMID: 17268555
7. Nicholson MJ, Moradi B, Seth NP, Xing X, Cuny GD, Stein RL, Wucherpfennig KW. Small molecules that enhance the catalytic efficiency of HLA-DM. J Immunol. 2006 Apr 1;176(7):4208-20. PMID: 16547258
8. Nicholson MJ, Hahn M, Wucherpfennig KW. Unusual features of self-peptide/MHC binding by autoimmune T cell receptors. Immunity. 2005 Oct;23(4):351-60. PMID: 16226501
9. Hahn M, Nicholson MJ, Pyrdol J, Wucherpfennig KW. Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor. Nat Immunol. 2005 May;6(5):490-6. PMID: 15821740

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Current Laboratory Members

Faculty Member: Melissa Call, BSc, MSc, PhD Auckland

Faculty Member: Matthew Call, BS Trinity PhD Harvard

Postdoctoral Fellow: Pooja Sharma, BPharm IIT-BHU (Banras Hindu), PhD Monash

Research Assistant: Mariam Lutfi, BSc Simon Fraser, BSc (Hons) Melbourne

UROP Student: Logesvaran Krshnan