Regulation of calcium signalling
Project type
Honours
| Supervisor(s) | Division | |
| (Primary) | Structural Biology | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Structural Biology | .(JavaScript must be enabled to view this email address) |
Details of project
Calcium signalling is essential for cell differentiation and development. Proliferation, gene expression and effector function require a ready supply of intracellular Ca2+. Stable, prolonged, Ca2+ influx across the plasma membrane is, for example, needed to promote calcineurin-activation of nuclear transcription factors that control expression of cytokines and chemokines. Store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) ion channels is the primary process responsible for sustained Ca2+ influx in T-cell lineages. CRAC currents are activated in response to antigen recognition by T lymphocytes, eliciting the adaptive immune response.
The symptoms in CRAC-deficient patients are dominated by compromised immunity as a result of defective T cell activation. A complex Ca2+-dependent interplay between binding partners in the cytosol and ER membrane is responsible for activation and inactivation of CRAC currents. These partners include, but are not limited to, calmodulin and STIM1. This project will involve the preparation and biochemical evaluation of cytoplasmic regulatory complexes, using minimal binding domains for structure determination.
Research interests
Cellular function is underpinned by the capacity to control the passage of molecules across membranes, and discrete macromolecular machineries have evolved for the transport of ions, metabolites and newly synthesised proteins.
Our interests lie in the mechanisms, regulation and interplay of systems facilitating membrane transport and cellular signalling, specifically protein translocation and ion conduction. The central methodology we use in elucidation of core mechanistic principles is X-ray crystallography. Please enquire about research opportunities for PhD projects in these areas.
Research theme
Chronic inflammatory diseases
Scientific discipline
- Structural Biology
Keywords
ion channels, calcium signalling