Moving in and renovating: Understanding the role of malaria proteins in erythrocyte remodeling
Project type
Honours and/or PhD
| Supervisor(s) | Division | |
| (Primary) | Infection and Immunity | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Infection and Immunity | .(JavaScript must be enabled to view this email address) |
Details of project
In this project, we seek to understand how exported virulence proteins are recognised in the parasite’s endoplasmic reticulum (ER) and trafficked to the host erythrocyte in which the parasite is growing. We have previously identified a protease (plasmepsin V) that recognizes the PEXEL motif in the ER and cleaves it to reveal a ‘barcode’ that is required for export. Our hypothesis is that this ‘barcode’ is recognised by other proteins in the ER that can direct trafficking into a specialised vesicular pathway for export through the translocon in the vacuole membrane.
This project will use a variety of methods to illuminate more of the pathway that virulence proteins take from ER to host erythrocyte. Techniques involved will include construction of genetically modified malaria parasites containing tagged proteins that may be involved in export. Immunoprecipitation and mass spectrometry will be used to determine if these tagged proteins are interacting with exported proteins or other proteins involved in trafficking. It will also involve construction of parasites in which specific genes have been mutated, deleted or placed under conditional regulation to turn them on or off. This will allow us to probe the function of specific proteins that may be essential for the parasite to renovate its erythrocyte in order to hide and survive. This project will be suited to both Honours and PhD candidates.
Project references
- Marti M, Good RT, Rug M, Knuepfer E, and Cowman AF. Targeting malaria virulence and remodelling proteins to the host erythrocyte. Science. 2004;306:1930-1933.
- Boddey JA, Hodder AN, Günther S, Gilson PR, Patsiouras H, Kapp EA, Pearce JA, de Koning-Ward TF, Simpson RJ, Crabb BS, and Cowman AF. An aspartyl protease directs malaria effector proteins to the host cell. Nature. 2010;463: 627-631.
- Goldberg DE, Cowman AF. Moving in and renovating: export of proteins into the Plasmodium-infected erythrocyte. Nat. Rev. Micro. 2010;8: 617-621.
Research interests
Malaria parasites undertake a large-scale infection of the bloodstream where they survive inside erythrocytes by drastically renovating them. This provides the parasites with a home to hide from immune defences and to obtain the nutrients they require for growth and replication. In order to accomplish this cellular renovation, the intracellular parasite exports hundreds of proteins into the erythrocyte to commandeer it for its own purposes.
We are interested in understanding the molecular basis of how the parasite achieves export for home renovation. An export motif, that we have named PEXEL, as well as a PEXEL recognition/processing enzyme, and a vacuole membrane translocon, have recently been identified in our laboratory. Important questions remain regarding how cleaved proteins traffic through the secretory pathway and are translocated across the vacuole membrane into the host cell. This export pathway may contain useful proteins that could be targeted by inhibitors that would interfere with the parasite’s virulence and survival programs.
Research theme
Infectious diseases
Scientific discipline
- Biochemistry
- Cell Biology
- Microbiology
- Molecular Biology
- Proteomics
Keywords
malaria, red blood cell, human