Understanding the structure and function of adhesins in invasion of malaria parasites
Project type
Honours and/or PhD
| Supervisor(s) | Division | |
| (Primary) | Infection and Immunity | .(JavaScript must be enabled to view this email address) |
Dr Wai-Hong Tham (Co-supervisor) |
Infection and Immunity | .(JavaScript must be enabled to view this email address) |
Dr Tony Hodder (Co-supervisor) |
Infection and Immunity | .(JavaScript must be enabled to view this email address) |
Details of project
Although the host erythrocyte receptors for some of the PfRh (Plasmodium falciparum reticulocyte-binding) and EBA (erythrocyte binding agent) ligands have been identified, nothing is known about the binding partners that assist these proteins in their role in invasion. The purpose of this project is to identify malaria parasite proteins that interact with both EBA175 and Rh4 in the invasion process.
We will isolate parasites in active invasion and perform immunoprecipitation experiments using monoclonal antibodies specific to EBA175 and Rh4. To definitively identify which proteins are in a complex with these invasion ligands, we will employ a combination of two-dimensional gel electrophoresis and mass spectrometry analyses.
To elucidate the function of any interacting parasite protein, we will utilise a repertoire of molecular and genetic tools readily available in our laboratory. In addition, we will also express various protein domains of the identified protein for the production of antibodies. We will also collaborate with Dr Peter Czabotar in the Structural Biology division to attempt to crystallise domains to determine their 3-dimensional structure. This work will allow us to decipher the role of these malaria parasite proteins in invasion using a variety of in vitro and in vivo assays.
This project would be suited to both Honours and PhD candidates.
Project references
- Cowman AF & Crabb BS. Invasion of red blood cells by malaria parasites. Cell. 2006;124(4):755-766.
- Tham WH, et al. Antibodies to reticulocyte binding protein-like homologue 4 inhibit invasion of Plasmodium falciparum into human erythrocytes. Infect. Immun. 2009;77(6):2427-2435.
- Stubbs J, et al. Molecular mechanism for switching of P. falciparum invasion pathways into human erythrocytes. Science. 2005;309(5739):1384-1387.
Research interests
To survive within humans, malaria parasites must invade host erythrocytes. Parasite invasion is initiated upon irreversible attachment of the parasite to the erythrocyte surface.
Research in our lab has focused on understanding the role of two families of parasite ligands, the erythrocyte binding antigen (EBA) and reticulocyte-binding like (Rh) proteins, that are involved in the recognition and attachment of malaria parasites to erythrocyte surface. In this project, we seek to understand the structure and function of these parasite ligands.
Research theme
Infectious diseases
Scientific discipline
- Biochemistry
- Cell Biology
- Microbiology
- Molecular Biology
- Proteomics
- Structural Biology
Keywords
malaria, human red blood cell, disease