A/Prof Call is a member of the Structural Biology Division at the Walter and Eliza Hall Institute (email address: firstname.lastname@example.org)
He shares a lab with Dr. Melissa Call. 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.