Role of exported proteins in the intracellular dynamics of liver-stage malaria
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
Several Honours and PhD projects that will build upon our recent discoveries of the export mechanism employed by intra-erythrocytic malaria parasites are available to students. These projects will seek to determine whether the export mechanism employed by malaria parasites during the blood-stage of infection is also employed during the liver-stage of disease. These exciting projects will also investigate the role of exported proteins in the intracellular dynamics of hepatocyte infection using both human and rodent malaria parasites with in vitro and in vivo models.
The work will involve molecular and cell biology and the use of the latest genetic techniques to manipulate parasites in order to knock down, delete and tag genes and proteins of interest in order to study their function. These isogenic parasites will be characterised using microscopy (fluorescence, confocal and electron), biochemistry, immuno-histochemistry, chemical biology, quantitative PCR and further transcriptional and proteomic analyses. Students will be working in an exciting, collaborative division that is comprised of many experts in parasitology, virology and bacteriology.
Project references
- Boddey JA, Hodder AN, Gunther S, Gilson PR, Patsiouras H, Kapp EA, Pearce JA, de Koning-Ward TF, Simpson RJ, Crabb BS, Cowman AF. An aspartyl protease directs malaria effector proteins to the host cell. Nature. 2010;463: 627-21. PMID: 20130643.
- deKoning-Ward TF, Gilson PR, Boddey JA, Rug M, Smith BJ, Papenfuss AT, Sanders PR, Lundie RJ, Maier AG, Cowman AF, Crabb BS. A newly discovered protein export machine in malaria parasites. Nature. 2009;459: 945-9. PMID: 19536257.
- Boddey JA, Moritz RL, Simpson RJ, Cowman AF. Role of the Plasmodium export element in trafficking parasite proteins to the infected erythrocyte. Traffic. 2009;10(3):285-99. PMID: 19055692.
- Kappe SHI, Vaughan AM, Boddey JA, Cowman AF. That Was Then But This Is Now: Malaria Research in the Time of an Eradication Agenda. Science. 2010;328(5980): 862-866. PMID: 20466924.
- Singh AP, Buscaglia CA, Wang Q, Levay A, Nussenzweig DR, Walker JR, Winzeler EA, Fujii H, Fontoura BM, Nussenzweig V. Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite. Cell. 2007;131(3):492-504. PMID: 17981117.
Research interests
Every year, several hundred million people contract malaria, resulting in approximately 1 million deaths. As such, malaria is one of the most pernicious infectious diseases in the world. Research that illuminates the molecular mechanisms allowing malaria parasites to survive within the host will help guide the development of new antimalarial therapies and a much-needed vaccine.
Malaria parasites survive inside red blood cells by exporting hundreds of proteins into the cell. These proteins renovate the cell, allowing the parasite to replicate and hide from the host immune system. Prior to blood-stage infection, malaria parasites silently thrive in the liver, developing in the tens of thousands per cell without eliciting an immune response. This intracellular secrecy is crucial to the parasite’s success because genetically weakened parasites, which arrest in the liver, are swiftly recognised and destroyed by the immune system. This primes immune defenses to recognise future malaria infections and rapidly clear them.
We are interested in characterising how the parasite influences the intracellular environment during liver infection and will investigate whether exported proteins play an important role. Our research will employ human and mouse models of malaria to address this question in the hope of identifying how the liver is established as a safe-haven for thousands of malaria parasites before they erupt into the blood stream to undertake a large-scale erythrocytic infection.
Research theme
Infectious diseases
Scientific discipline
- Biochemistry
- Cell Biology
- Genetics
- Microbiology
- Molecular Biology
- Proteomics
Keywords
Malaria, protein trafficking, virulence, pathogen-host interactions, molecular microbiology