close search

Discovering novel antimalarials to block parasite virulence

Drugs are the main weapons used to combat malaria infection, but parasites are becoming resistant and new medicines and drug targets are needed. One potential target is the protein trafficking pathways parasites and PTEX machine used to deliver proteins within their own cells and the human red blood cells the parasites infect. If the protein trafficking system could be blocked this would kill the parasites and eliminate malaria.

We aim to understand the biology underpinning malaria parasite virulence and use this knowledge to aid our discovery and development of novel antimalarials that reduce the parasites’ ability to harm its human host. 

2009–ongoing

We perform a range of biochemical, cell biological and plate-based assays to understand basic parasite biology and virulence. We have developed a novel luminescence-based screening platform to discover novel antimalarials that target parasite components that are essential for parasite survival.

Better, safer, and cheaper antimalarial drugs would benefit endemic communities around the world and could accelerate malaria elimination. The research will also provide new knowledge about parasite biology that could inform future treatment options.

Associate Professor Paul Gilson

Contact Associate Professor Paul Gilson for more information about this project. 

EMAIL

Funding
Partners

  • National Health and Medical Research Council (NHMRC)

Partners +
Collaborators

  • Deakin University (Tania de Koning-Ward)
  • WEHI (Brad Sleebs, William Nguyen)
  • Deakin University/Burnet Institute (Alyssa Barry)
  • Monash University (Darren Creek, Ghizal Siddiqui)

Project
Team

Meet the project team. Together, we are translating research into better health, for all.

Professor Brendan Crabb AC

DIRECTOR AND CEO; CO-HEAD, MALARIA VIRULENCE AND DRUG DISCOVERY GROUP; CHAIR AUSTRALIAN GLOBAL HEALTH ALLIANCE AND CHAIR PACIFIC FRIENDS OF GLOBAL HEALTH

Professor Brendan Crabb AC PhD FAA FAHMS FASM is an infectious disease researcher with a special int...

Associate Professor Paul Gilson

DEPUTY DISCIPLINE HEAD, LIFE SCIENCES; CO-HEAD, MALARIA VIRULENCE AND DRUG DISCOVERY GROUP; HEAD OF BURNET CELL IMAGING FACILITY

Paul Gilson is a molecular biologist primarily interested in how malaria parasites invade...

Claudia Barnes

RESEARCH ASSISTANT

After completing the Bachelor of Biomedicine at The University of Melbourne, Claudia undertook an Ho...

Doctor Hayley Bullen

DEPUTY WORKING GROUP HEAD, MALARIA VIRULENCE AND DRUG DISCOVERY GROUP

After completing her Bachelor of Biomedical Science degree in 2006, Hayley went on to pursue her...

Professor Brendan Crabb AC

DIRECTOR AND CEO; CO-HEAD, MALARIA VIRULENCE AND DRUG DISCOVERY GROUP; CHAIR AUSTRALIAN GLOBAL HEALTH ALLIANCE AND CHAIR PACIFIC FRIENDS OF GLOBAL HEALTH

Professor Brendan Crabb AC PhD FAA FAHMS FASM is an infectious disease researcher with a special int...

Associate Professor Paul Gilson

DEPUTY DISCIPLINE HEAD, LIFE SCIENCES; CO-HEAD, MALARIA VIRULENCE AND DRUG DISCOVERY GROUP; HEAD OF BURNET CELL IMAGING FACILITY

Paul Gilson is a molecular biologist primarily interested in how malaria parasites invade...

Doctor Oliver Looker

POSTDOCTORAL SCIENTIST

After obtaining a Bachelor of Science degree in 2013, Oliver completed an honours project under Prof...

Molly Schneider

RESEARCH ASSISTANT

Molly completed her Bachelor of Science with Honours in 2016 at the University of Melbourne. Her res...

Publications

VIEW ALL RESEARCH
Sequence elements within the PEXEL motif and its downstream region modulate PTEX-dependent protein export in Plasmodium falciparum.

Gabriela M, Barnes CBG, Leong D, Sleebs BE, Schneider MP, Littler DR, Crabb BS, de Koning-Ward TF, Gilson PR

  • 05 Nov 2023
Malaria
PTEX helps efficiently traffic haemoglobinases to the food vacuole in Plasmodium falciparum.

Jonsdottir TK, Elsworth B, Cobbold S, Gabriela M, Ploeger E, Parkyn Schneider M, Charnaud SC, Dans MG, McConville M, Bullen HE, Crabb BS, Gilson PR

  • PLoS pathogens
  • 31 Jul 2023
Malaria
The delayed bloodstream clearance of Plasmodium falciparum parasites after M5717 treatment is attributable to the inability to modify their red blood cell hosts.

Schneider MP, Looker O, Rebelo M, Khoury DS, Dixon MWA, Oeuvray C, Crabb BS, McCarthy J, Gilson PR

  • Frontiers in cellular and infection microbiology
  • 29 Jun 2023
Malaria
A Pyridyl-Furan Series Developed from the Open Global Health Library Block Red Blood Cell Invasion and Protein Trafficking in <i>Plasmodium falciparum</i> through Potential Inhibition of the Parasite's PI4KIIIB Enzyme.

Ling DB, Nguyen W, Looker O, Razook Z, McCann K, Barry AE, Scheurer C, Wittlin S, Famodimu MT, Delves MJ, Bullen HE, Crabb BS, Sleebs BE, Gilson PR

  • ACS infectious diseases
  • 28 Aug 2023
Malaria
A revised mechanism for how Plasmodium falciparum recruits and exports proteins into its erythrocytic host cell.

Gabriela M, Matthews KM, Boshoven C, Kouskousis B, Jonsdottir TK, Bullen HE, Modak J, Steer DL, Sleebs BE, Crabb BS, de Koning-Ward TF, Gilson PR

  • PLoS pathogens
  • 22 Feb 2022
Malaria
The Plasmodium falciparum parasitophorous vacuole protein P113 interacts with the parasite protein export machinery and maintains normal vacuole architecture.

Bullen HE, Sanders PR, Dans MG, Jonsdottir TK, Riglar DT, Looker O, Palmer CS, Kouskousis B, Charnaud SC, Triglia T, Gabriela M, Parkyn Schneider M, Chan JA, de Koning-Ward TF, Baum J, Kazura JW, Beeson JG, Cowman AF, Gilson PR, Crabb BS

  • Molecular microbiology
  • 25 Apr 2022
Malaria
The Medicines for Malaria Venture Malaria Box contains inhibitors of protein secretion in Plasmodium falciparum blood stage parasites.

Looker O, Dans MG, Bullen HE, Sleebs BE, Crabb BS, Gilson PR

  • Traffic (Copenhagen, Denmark)
  • 15 Aug 2022
Malaria
Characterisation of complexes formed by parasite proteins exported into the host cell compartment of Plasmodium falciparum infected red blood cells.

Jonsdottir TK, Counihan NA, Modak JK, Kouskousis B, Sanders PR, Gabriela M, Bullen HE, Crabb BS, de Koning-Ward TF, Gilson PR

  • Cellular microbiology
  • 03 May 2021
Malaria
Defining the Essential Exportome of the Malaria Parasite.

Jonsdottir TK, Gabriela M, Crabb BS, F de Koning-Ward T, Gilson PR

  • Trends in parasitology
  • 10 May 2021
Malaria
The Role of Malaria Parasite Heat Shock Proteins in Protein Trafficking and Remodelling of Red Blood Cells.

Jonsdottir TK, Gabriela M, Gilson PR

  • Advances in experimental medicine and biology
  • 28 Sep 2021
Malaria
The N-terminus of EXP2 forms the membrane-associated pore of the protein exporting translocon PTEX in Plasmodium falciparum.

Sanders PR, Dickerman BK, Charnaud SC, Ramsland PA, Crabb BS, Gilson PR

  • Journal of biochemistry
  • 03 Apr 2019
Malaria
The malaria PTEX component PTEX88 interacts most closely with HSP101 at the host-parasite interface.

Chisholm SA, Kalanon M, Nebl T, Sanders PR, Matthews KM, Dickerman BK, Gilson PR, de Koning-Ward TF

  • The FEBS journal
  • 20 Apr 2018
Malaria
Spatial organization of protein export in malaria parasite blood stages.

Charnaud SC, Jonsdottir TK, Sanders PR, Bullen HE, Dickerman BK, Kouskousis B, Palmer CS, Pietrzak HM, Laumaea AE, Erazo AB, McHugh E, Tilley L, Crabb BS, Gilson PR

  • Traffic (Copenhagen, Denmark)
  • 23 May 2018
Malaria
Plasmepsin V cleaves malaria effector proteins in a distinct endoplasmic reticulum translocation interactome for export to the erythrocyte.

Marapana DS, Dagley LF, Sandow JJ, Nebl T, Triglia T, Pasternak M, Dickerman BK, Crabb BS, Gilson PR, Webb AI, Boddey JA, Cowman AF

  • Nature microbiology
  • 20 Aug 2018
Malaria
Knockdown of the translocon protein EXP2 in Plasmodium falciparum reduces growth and protein export.

Charnaud SC, Kumarasingha R, Bullen HE, Crabb BS, Gilson PR

  • PloS one
  • 15 Nov 2018
Malaria