Structural studies of the Plasmodium and Toxoplasma tight-junction complex

Structural studies of the Plasmodium and Toxoplasma tight-junction complex

Project details

Apicomplexan parasites such as those causing malaria (Plasmodium spp) and toxoplasmosis (Toxoplasma) must invade host cells to complete their life cycle. At the onset of invasion these parasites inject their own receptor – the ‘RON complex’ - into the host cell membrane and then use their adhesin ‘AMA1’ for its recognition and subsequent host cell penetration. Thus, the AMA1-RON interaction is critical for invasion. 

Despite this critical importance and its potential as a vaccine target, little is known about how this AMA1-RON complex functions nor how we might target this complex in the design of new therapies. 

This exciting project will reveal the structural basis of the AMA1-RON complex using the latest technology in electron cryomicroscopy (cryoEM). Protein complexes will be both recombinantly expressed and purified natively from parasite cultures to reveal its atomic structure. This information will provide a fundamental understanding of host-parasite interactions and develop critical information for the design of new therapeutics for the treatment of toxoplasmosis and malaria.

About our research group

Apicomplexan parasites are protozoan pathogens that cause major infectious diseases in humans. Notably, these include Plasmodium and Toxoplasma species that cause malaria and toxoplasmosis respectively. To complete their development, they must identify and invade suitable host cells to establish an intracellular niche for growth and replication. Invasion is a complex process that involves many parasite ligands interacting with the cognate host cell receptors required for parasite entry. 

Our research groups are interested in characterising the structures and mechanisms of ligand-receptor interactions that enable apicomplexan parasites to invade their host, and using this knowledge to form the basis vaccine and drug design to target these pathogens.

The Tonkin and Cowman laboratories use parasite molecular genetics, protein purification techniques and electron cryomicroscopy (cryo-EM) for structure determination.

 

Researchers:

Wilson Wong in the lab
Dr
Wilson
Wong
Infection and Immunity division

Professor Alan Cowman

Professor Alan Cowman in the lab
Professor
Alan
Cowman
Deputy Director and Joint Division Head

Project Type: