Justin Boddey-Projects

Justin Boddey-Projects

Researcher: 

Projects

Molecular mechanisms of hepatocyte traversal and invasion by Plasmodium falciparum

A fundamental step in human infection by P. falciparum is the traversal and invasion of human hepatocytes. The molecular basis for these interactions is almost completely unknown.

This project uses genetic techniques to tag or disrupt proteins that may be involved in these processes and to examine the consequences on the parasite and host at the subcellular and cellular level. A clearer understanding of how parasites interact with human hepatocytes will allow us to augment it for downstream applications as well as to potentially block it for therapeutic purposes.

Team members: Annie Yang, Matthew O’Neill, Sash Lopaticki

Molecular mechanisms of protein export during liver stage malaria and during infection by Toxoplasma

The protein export pathway has been studied most in the blood stage of malaria. This project investigates whether the export pathway used to remodel erythrocytes is employed during liver infection by P. falciparum and P. berghei parasites. The project involves molecular parasitology and cell biology using in vitro and humanised models.

The second component of this project investigates whether the export pathway in malaria parasites is also employed by the closely related Apicomplexan parasite, Toxoplasma gondii, which is a parasite of cats and humans and causes mental ilnesses.

Malaria lifecycle diagram
Malaria lifecycle (left) and the liver stage of P. falciparum in a humanised model of infection (right)

Team members: Pravin Rajasekaran, Matthew O’Neill, Michael Coffey

Role of exported proteins in transmission and liver stages of malaria

Exported proteins play a variety of roles in the infected erythrocyte; do exported proteins also play key roles at other stages of the lifecycle?

This project involves the development of transgenic P. falciparum and P. berghei parasites with proteins tagged or deleted and examining the functional consequences of the deletion on parasite transmission and development, from gametocytes through to liver stage forms. It also involves defining the subcellular localization of the proteins across the lifecycle. 

Team members: Jennifer Armistead, Pravin Rajasekaran, Charlie Jennison, Matthew O’Neill, Sash Lopaticki

Plasmepsin V inhibitors as export blocking compounds and antimalarials

Plasmepsin V processing of the PEXEL can be blocked with inhibitors.

This project is to develop a second-generation small molecule inhibitor with the hope that it is effective in vivo and in humans. The project uses structure-guided medicinal chemistry to develop small molecule leads into plasmepsin V inhibitors for use in cell biological studies across the lifecycle as well as in humans. The project involves medicinal chemistry and chemical biology as well as structural biology, cell biology and molecular parasitology.

Malaria infection diagram
Inhibition of protein export by blocking the malarial enzyme plasmepsin V kills the parasite

 

Team members: Brad Sleebs, Michelle Gazdik, Matthew O’Neill, Sash Lopaticki