Discovering how malaria parasites survive inside human red blood cells
Malaria remains a major global health burden causing hundreds of millions of debilitating infections per year that tragically result in over half a million deaths.
The mosquito borne Plasmodium parasites, which cause malaria, invade and grow inside human red blood cells (RBCs). RBCs are ideal places for parasites to live because they are relatively invisible to the immune system, and they can be taken up by mosquitoes for transmission to others.
The disadvantages are that RBCs are nutrient poor and are monitored by the spleen where circulating parasite infected RBCs are destroyed. For these reasons, malaria parasites extensively modify their RBCs to obtain supplementary nutrients, elude the immune system and avoid destruction in the spleen.
Within an infected RBC, the parasite hides within a specialised membrane sac termed the parasitophorous vacuole. To survive within this protected niche, the parasite must export hundreds of proteins into the RBC compartment. These proteins help the parasite take up nutrients from its host and are also involved in remodelling the RBC to make it sticky; by sticking to the walls of blood vessels, the infected RBC avoids clearance by the spleen and the parasite has the opportunity to grow, cause disease symptoms, and transmit to others. The proteins involved in RBC remodelling enter the RBC following passage through a protein translocon called PTEX.
Exported proteins contain a molecular barcode, called a PEXEL motif, that is scanned by PTEX, allowing only a specific subset of parasite proteins access to the RBC. Of these exported proteins, ~70 are believed to be essential for parasite survival. Importantly, the roles of many of these essential proteins remain completely undefined, meaning that we have no idea how they contribute to parasite survival. If we can decipher how these proteins work, we are likely to uncover completely new ways in which the parasite can be targeted and killed by new therapeutics. Discovering how these essential exported proteins contribute to parasite survival is the key focus of this project.
This project involves an array of state-of-the-art molecular biology, biochemical and microscopy techniques to define the function of essential exported proteins in malaria parasites. This work will be completed in the two main species of malaria that can be cultured in the lab: P. falciparum and P. knowlesi.
Student opportunities
Discovering how malaria parasites survive inside human red blood cells
Skills that will be acquired during this project include parasite cell culture, molecular biology including CRISPR/Cas9 based transfection techniques, immunofluorescence and expansion microscopy, mass spectrometry and basic biochemistry.
Open to
- Honours
- PhD
Vacancies
2
Supervisors
Featured publications
A newly discovered protein export machine in malaria parasites
Nature
Tania F. de Koning‐Ward et al
PTEX is an essential nexus for protein export in malaria parasites
Nature
Brendan Elsworth et al
Sequence elements within the PEXEL motif and its downstream region modulate PTEX dependent protein export in Plasmodium falciparum .
Authorea (Authorea)
Paul R. Gilson et al
Biosynthesis, Localization, and Macromolecular Arrangement of the Plasmodium falciparum Translocon of Exported Proteins (PTEX)
Journal of Biological Chemistry
Hayley E. Bullen et al
Dissecting EXP2 sequence requirements for protein export in malaria parasites
Frontiers in Cellular and Infection Microbiology
Ethan L. Pitman et al
A Pyridyl-Furan Series Developed from the Open Global Health Library Block Red Blood Cell Invasion and Protein Trafficking in Plasmodium falciparum through Potential Inhibition of the Parasite’s PI4KIIIB Enzyme
ACS Infectious Diseases
Dawson B. Ling et al
PTEX helps efficiently traffic haemoglobinases to the food vacuole in Plasmodium falciparum
PLoS Pathogens
Thorey K. Jonsdottir et al
The Medicines for Malaria Venture Malaria Box contains inhibitors of protein secretion in Plasmodium falciparum blood stage parasites
Traffic
Oliver Looker et al
The Plasmodium falciparum parasitophorous vacuole protein P113 interacts with the parasite protein export machinery and maintains normal vacuole architecture
Molecular Microbiology
Hayley E. Bullen et al
A revised mechanism for how Plasmodium falciparum recruits and exports proteins into its erythrocytic host cell
PLoS Pathogens
Mikha Gabriela et al
The Role of Malaria Parasite Heat Shock Proteins in Protein Trafficking and Remodelling of Red Blood Cells
Advances in experimental medicine and biology
Thorey K. Jonsdottir, Mikha Gabriela, Paul R. Gilson
Defining the Essential Exportome of the Malaria Parasite
Trends in Parasitology
Thorey K. Jonsdottir et al
Characterisation of complexes formed by parasite proteins exported into the host cell compartment of Plasmodium falciparum infected red blood cells
Cellular Microbiology
Thorey K. Jonsdottir et al
Knockdown of the translocon protein EXP2 in Plasmodium falciparum reduces growth and protein export
PLoS ONE
Sarah C. Charnaud et al
Spatial organization of protein export in malaria parasite blood stages
Traffic
Sarah C. Charnaud et al
The exported chaperone Hsp70-x supports virulence functions for Plasmodium falciparum blood stage parasites
PLoS ONE
Sarah C. Charnaud et al
Plasmodium falciparum parasites deploy RhopH2 into the host erythrocyte to obtain nutrients, grow and replicate
eLife
Natalie A. Counihan et al
Proteomic analysis reveals novel proteins associated with thePlasmodiumprotein exporter PTEX and a loss of complex stability upon truncation of the core PTEX component, PTEX150
Cellular Microbiology
Brendan Elsworth et al
Host cell remodelling in malaria parasites: a new pool of potential drug targets
International Journal for Parasitology
Paul R. Gilson et al
Spatial association with PTEX complexes defines regions for effector export into Plasmodium falciparum-infected erythrocytes
Nature Communications
David T. Riglar et al
The N-terminus of EXP2 forms the membrane-associated pore of the protein exporting translocon PTEX in Plasmodium falciparum
The Journal of Biochemistry
Paul R. Sanders et al
Partners
Funding partners
- National Health and Medical Research Council (NHMRC) Investigator Grant
Collaborators
- Monash Institute of Pharmaceutical Sciences (MIPS)
- Deakin University
- University of Adelaide
Project contacts
Main contacts
Student supervisor contacts

Associate Professor Paul Gilson
Deputy Discipline Head, Life Sciences; Co-Head Malaria Virulence, Drug Discovery and Resistance; Head of Burnet Cell Imaging Facility

Dr Hayley Bullen
Co-Head Malaria Virulence, Drug Discovery and Resistance
Project team

Associate Professor Paul Gilson
Deputy Discipline Head, Life Sciences; Co-Head Malaria Virulence, Drug Discovery and Resistance; Head of Burnet Cell Imaging Facility
