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Drug resistance and mechanism of action studies

Drugs are the main weapons used to combat malaria infection, but parasites are becoming resistant and new medicines and drug targets are needed. Through a broad range of biochemical, cell biology and molecular biology methods we are deciphering how different novel antimalarials work. We work with medicinal chemists who improve the potency and specificity of a range of novel and repurposed drugs, to develop new antimalarials that are effective against already multi-drug resistant parasites.

We seek to repurpose commercial compounds for use against malaria parasites and investigate how parasites become resistant to current antimalarial compounds. 

2015–ongoing

We use state-of-the-art genetic modification tools, including CRISPR/Cas9, alongside whole genome sequencing and a range of biochemical and plate-based assays to decipher how antimalarial compounds we have discovered act to kill the parasites.

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.

Hayley Bullen

Dr Hayley Bullen

Contact Dr Hayley Bullen for more information about this project. 

EMAIL

Funding
Partners

  • National Health and Medical Research Council (NHMRC)

Partners +
Collaborators

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

Project
Team

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

Hayley Bullen
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...

Claudia.Barnes
Claudia Barnes

RESEARCH ASSISTANT

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

Hayley Bullen
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...

390X452 Brendan Crabb 003 2 Print Cropped
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...

Square Paul Gilson210 X 210
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...

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Doctor Oliver Looker

POSTDOCTORAL SCIENTIST

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

Square Molly.Pschneider
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
Protein disulfide isomerases - a way to tackle malaria.

Angrisano F, Ford A, Blagborough AM, Bullen HE

  • Trends in Parasitology
  • 09 Jun 2023
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Property activity refinement of 2-anilino 4-amino substituted quinazolines as antimalarials with fast acting asexual parasite activity.

Ashton TD, Ngo A, Favuzza P, Bullen HE, Gancheva MR, Romeo O, Parkyn Schneider M, Nguyen N, Steel RWJ, Duffy S, Lowes KN, Sabroux HJ, Avery VM, Boddey JA, Wilson DW, Cowman AF, Gilson PR, Sleebs BE

  • Bioorganic chemistry
  • 21 Sep 2021
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Evaluation of 4-Amino 2-Anilinoquinazolines against Plasmodium and Other Apicomplexan Parasites In Vitro and in a P. falciparum Humanized NOD- scid IL2Rγnull Mouse Model of Malaria.

Gilson PR, Nguyen W, Poole WA, Teixeira JE, Thompson JK, Guo K, Stewart RJ, Ashton TD, White KL, Sanz LM, Gamo FJ, Charman SA, Wittlin S, Duffy J, Tonkin CJ, Tham WH, Crabb BS, Cooke BM, Huston CD, Cowman AF, Sleebs BE.

  • 26 Feb 2019
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A 4-cyano-3-methylisoquinoline inhibitor of Plasmodium falciparum growth targets the sodium efflux pump PfATP4.

Gilson PR, Kumarasingha R, Thompson J, Zhang X, Penington JS, Kalhor R, Bullen HE, Lehane AM, Dans MG, de Koning-Ward TF, Holien JK, Soares da Costa TP, Hulett MD, Buskes MJ, Crabb BS, Kirk K, Papenfuss AT, Cowman AF, Abbott BM

  • Scientific reports
  • 16 Jul 2019
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Optimization of 2-Anilino 4-Amino Substituted Quinazolines into Potent Antimalarial Agents with Oral in Vivo Activity.

Gilson PR, Tan C, Jarman KE, Lowes KN, Curtis JM, Nguyen W, Di Rago AE, Bullen HE, Prinz B, Duffy S, Baell JB, Hutton CA, Jousset Subroux H, Crabb BS, Avery VM, Cowman AF, Sleebs BE

  • Journal of medicinal chemistry
  • 26 Jan 2017
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Sulfonylpiperazine compounds prevent Plasmodium falciparum invasion of red blood cells through interference with actin-1/profilin dynamics.

Dans MG, Piirainen H, Nguyen W, Khurana S, Mehra S, Razook Z, Geoghegan ND, Dawson AT, Das S, Parkyn Schneider M, Jonsdottir TK, Gabriela M, Gancheva MR, Tonkin CJ, Mollard V, Goodman CD, McFadden GI, Wilson DW, Rogers KL, Barry AE, Crabb BS, de Koning-Ward TF, Sleebs BE, Kursula I, Gilson PR

  • PLoS biology
  • 13 Apr 2023
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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
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Identification of inhibitors that dually target the new permeability pathway and dihydroorotate dehydrogenase in the blood stage of Plasmodium falciparum.

Dickerman BK, Elsworth B, Cobbold SA, Nie CQ, McConville MJ, Crabb BS, Gilson PR

  • Scientific reports
  • 22 Nov 2016
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Hierarchical phosphorylation of apical membrane antigen 1 is required for efficient red blood cell invasion by malaria parasites.

Prinz B, Harvey KL, Wilcke L, Ruch U, Engelberg K, Biller L, Lucet I, Erkelenz S, Heincke D, Spielmann T, Doerig C, Kunick C, Crabb BS, Gilson PR, Gilberger TW

  • Scientific reports
  • 04 Oct 2016
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PfATP4 inhibitors in the Medicines for Malaria Venture Malaria Box and Pathogen Box block the schizont-to-ring transition by inhibiting egress rather than invasion.

Barnes CBG, Dans MG, Jonsdottir TK, Crabb BS, Gilson PR

  • Frontiers in cellular and infection microbiology
  • 30 Nov 2022
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