A/Prof Justin Boddey, Lab Head | WEHI Researcher Profile

Q: 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.

Q: 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.

Q: 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.

Q: 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.

About

Our laboratory is interested in understanding how malaria parasites manipulate their intracellular environment in order to live within humans.

We are examining:

How the parasite enters liver cells.
How the parasite survives inside liver cells.
How the parasite is transmitted to, and develops within, mosquitoes.
Our recent research has focused on how malaria parasites commandeer red blood cells by exporting their own proteins into these cells. This has revealed potential new targets for antimalarial treatments. We are very keen to see whether these parasite targets are also active during the earliest and last phases of malaria in the human host, in order to intercept the parasite at multiple stages of its lifecycle.

We use cell biology and biochemistry to study the parasite and its interactions with the host. We also utlise the institute’s new insectary, in which Anopheles stenphensi mosquitoes are reared and can be infected with P. falciparum, P. vivax and P. berghei parasites. We use in vitro and humanised models to study malaria-host interactions across the lifecycle.

Our research also involves the development of small molecule inhibitors for use as tools to understand the role of protein export across the lifecycle, and also for potential use as antiparasitic therapies.

Education

Grants and funding

Publications

Selected publications from A/Prof Justin Boddey

Boddey JA, Frischknecht F. Interferoning with Plasmodium development in the liver. Cell Host & Microbe. 2025;33(4):10.1016/j.chom.2025.03.007

Zanghí G, Patel H, Smith JL, Camargo N, Bae Y, Hesping E, Boddey JA, Venugopal K, Marti M, Flannery EL, Chuenchob V, Fishbaugher ME, Mikolajczak SA, Roobsoong W, Sattabongkot J, Gupta P, Pazzagli L, Rezakhani N, Betz W, Hayes K, Goswami D, Vaughan AM, Kappe SHI. Genome-wide gene expression profiles throughout human malaria parasite liver stage development in humanized mice. Nature Microbiology. 2025;10(2):10.1038/s41564-024-01905-5

Wang L, Qu J, Harari O, Boddey JA, Wang Z, Linna-Kuosmanen S. The impact of multi-omics in medicine. Cell Reports Medicine. 2024;5(9):10.1016/j.xcrm.2024.101742

Angage D, Chmielewski J, Maddumage JC, Hesping E, Caiazzo S, Lai KH, Yeoh LM, Menassa J, Opi DH, Cairns C, Puthalakath H, Beeson JG, Kvansakul M, Boddey JA, Wilson DW, Anders RF, Foley M. A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites. Nature Communications. 2024;15(1):10.1038/s41467-024-50770-7

Darif N-D, Ganter M, Dziekan JM, Kilian N, Brancucci N, Ng C, de Vries LE, Guttery D, Philip N, Boddey JA, Metwally NG, Okumu F, Kooij TWA, Absalon S, Bryant JM. BioMalPar XX: looking back on, and forward from, 20 years of malaria research. Trends in Parasitology. 2024;40(8):10.1016/j.pt.2024.06.012

McConville R, Krol JMM, Steel RWJ, O’Neill MT, Davey BK, Hodder AN, Nebl T, Cowman AF, Kneteman N, Boddey JA. Flp/FRT-mediated disruption of ptex150 and exp2 in Plasmodium falciparum sporozoites inhibits liver-stage development. Proceedings of the National Academy of Sciences of the United States of America. 2024;121(28):10.1073/pnas.2403442121

Hesping E, Boddey JA. Whole‐genome CRISPR screens to understand Apicomplexan–host interactions. Molecular Microbiology. 2024;121(4):10.1111/mmi.15221

Preston SP, Stutz MD, Allison CC, Nachbur U, Gouil Q, Tran BM, Duvivier V, Arandjelovic P, Cooney JP, Mackiewicz L, Meng Y, Schaefer J, Bader SM, Peng H, Valaydon Z, Rajasekaran P, Jennison C, Lopaticki S, Farrell A, Ryan M, Howell J, Croagh C, Karunakaran D, Schuster-Klein C, Murphy JM, Fifis T, Christophi C, Vincan E, Blewitt ME, Thompson A, Boddey JA, Doerflinger M, Pellegrini M. Epigenetic Silencing of RIPK3 in Hepatocytes Prevents MLKL-mediated Necroptosis From Contributing to Liver Pathologies. Gastroenterology. 2022;163(6):10.1053/j.gastro.2022.08.040

Clucas D, Bennett C, Steel R, Mellin R, Caiazzo S, Schaeper U, Boddey J, Ataide R, Pasricha S-R. Tmprss6 Depletion-Mediated Iron Deficiency Attenuates the Clinical Course of Plasmodium Berghei Infection in Mice. Blood. 2022;140(Supplement 1):10.1182/blood-2022-165823

de Lera Ruiz M, Favuzza P, Guo Z, Zhao L, Hu B, Lei Z, Zhan D, Murgolo N, Boyce CW, Vavrek M, Thompson J, Ngo A, Jarman KE, Robbins J, Boddey J, Sleebs BE, Lowes KN, Cowman AF, Olsen DB, McCauley JA. The Invention of WM382, a Highly Potent PMIX/X Dual Inhibitor toward the Treatment of Malaria. ACS Medicinal Chemistry Letters. 2022;13(11):10.1021/acsmedchemlett.2c00355