How do malaria parasites signal for invasion?
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) |
Details of project
We seek to understand the role of the cytoplasmic tail of Rh4. To do so, we will express mutated or truncated forms for this domain endogenously in the parasite. These modified parasite strains will allow us to ask the importance of the tail in localisation of the protein and also its effect on parasite invasion.
In addition, we will also express recombinant versions of this domain in bacteria cells. We will test these recombinant proteins in in vitro phosphorylation assays to examine if this domain undergoes post-translational modification. Furthermore we will generate antibodies to this domain which will allow us to follow the fate of the cytoplasmic tails in parasite invasion.
This project is suitable for both Honours or PhD candidates.
Research interests
During the asexual stage of Plasmodium falciparum lifecycle, the parasite undergoes rapid replication within the blood cells (erythrocytes) of the human host, resulting in the clinical manifestations seen in malaria infections. The merozoite forms of P. falciparum invade erythrocytes through a multi-step process that involves initial contact with the erythrocyte, apical reorientation of the merozoite and the formation of a tight junction which moves progressively towards the posterior end of the parasite until host cell membrane fusion is completed. These steps in invasion are dependent on specific interactions between multiple parasite invasion ligands and their respective host erythrocyte receptor.
One of the parasite ligands that mediates attachment to the erythrocyte is reticulocyte binding like homologue 4 (Rh4). Rh4 binds to its host erythrocyte receptor complement receptor 1 (CR1) to commence a cascade of signaling events leading to the completion of the invasion process. Presently, nothing is known about the molecular mechanism that Rh4 employs for the initiation of active invasion. In proteins homologous to Rh4, removal of the cytoplasmic tail results in a defect in parasite invasion suggesting that this domain is essential in invasion and plays an important role in signaling events.
Selected publications
- Cowman AF and 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.
- Tham W-H, Wilson DW, Lopaticki S, Schmidt CQ, Tetteh-Quarcoo PB, Barlow PN, Richard D, Corbin JE, Beeson JG, Cowman AF. Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand. Proc Natl Acad Sci. 2010. 107(40):17327-32.
- Tham WH, Schmidt CQ, Hauhart RE, Guariento M, Tetteh-Quarcoo PB, Lopaticki S, Atkinson JP, Barlow PN, Cowman AF. Plasmodium falciparum uses a key functional site in complement receptor type-1 for invasion of human erythrocytes. Blood. 2011 Jun 17. [Epub ahead of print]
Research theme
Infectious diseases
Scientific discipline
- Biochemistry
- Microbiology
- Molecular Biology
Keywords
malaria, phosphorylation, signalling