Our research is aimed at understanding the unique biology of the malaria parasite Plasmodium falciparum, with a particular focus on virulence and transmission.

We are investigating:

  • how parasites renovate their RBC home to drive virulence and transmission
  • how the parasite makes the banana-shaped sexual blood stage gametocyte
  • how this shape helps them survive in the host and be efficiently transmitted
  • how parasites behave inside the human host in vivo
  • how effective specific drugs and vaccines are at blocking transmission of gametocytes from infected humans to Anopheles mosquitos.

In these projects, we will use CRISPR gene editing to create transgenic malaria parasites, which we will study by combing proteomics, molecular and cellular biology techniques with super resolution microscopy to define the molecular players driving gametocyte development and transmission.

This in vitro work will be complimented by ex vivo examination of samples from experimental human malaria infection studies, which are focused on identifying and confirming the activity of candidate transmission blocking drugs and vaccines.

A combined in vitro and in vivo approach to understanding how gametocytes mature will inform the development of effective means of combating this debilitating disease.

Professor McCarthy holds a joint appointment as Director of the Victorian Infectious Diseases Service at the Royal Melbourne Hospital, and Professor of Medicine at the Doherty Institute where he leads the Translational Models of Infectious Diseases group that focusses on human infection challenge models to develop drugs and vaccines.


Selected publications from Prof James McCarthy

1. Collins KA, Abd-Rahman AN, Marquart L, Ballard E, Gobeau N, Griffin P, Chalon S, Mohrle JJ, McCarthy JS. Antimalarial activity of artefenomel against asexual parasites and transmissible gametocytes during experimental blood-stage Plasmodium vivax infection. J Infect Dis. 2020 Jun 1;jiaa287. PMID: 32479608

2. Collins KA, Wang CY, Adams M, Mitchell H, Robinson GJ, Rampton M, Elliott S, Odedra A, Khoury D, Ballard E, Shelper TB, Lucantoni L, Avery VM, Chalon S, Moehrle JJ, McCarthy JS. A Plasmodium vivax experimental human infection model for evaluating efficacy of interventions. J Clin Invest. 2020;130(6):2920-7. PMID: 32045385

3. Prajapati SK, Ayanful-Torgby R, Pava Z, Barbeau MC, Acquah FK, Cudjoe E, Kakaney C, Amponsah JA, Obboh E, Ahmed AE, Abuaku BK, McCarthy JS, Amoah LE, Williamson KC. The transcriptome of circulating sexually committed Plasmodium falciparum ring stage parasites forecasts malaria transmission potential. Nat Commun. 2020;11(1):6159. PMID: 33268801

4. Vijay R, Guthmiller JJ, Sturtz AJ, Surette FA, Rogers KJ, Sompallae RR, Li F, Pope RL, Chan JA, de Labastida Rivera F, Andrew D, Webb L, Maury WJ, Xue HH, Engwerda CR, McCarthy JS, Boyle MJ, Butler NS. Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria. Nat Immunol. 2020;21(7):790-801. PMID: 32424361

5. Watts RE, Odedra A, Marquart L, Webb L, Abd-Rahman AN, Cascales L, Chalon S, Rebelo M, Pava Z, Collins KA, Pasay C, Chen N, Peatey CL, Mohrle JJ, McCarthy JS. Safety and parasite clearance of artemisinin-resistant Plasmodium falciparum infection: A pilot and a randomised volunteer infection study in Australia. PLoS Med. 2020;17(8):e1003203. PMID: 32822347

6. Cao P, Collins KA, Zaloumis S, Wattanakul T, Tarning J, Simpson JA, McCarthy J, McCaw JM. Modeling the dynamics of Plasmodium falciparum gametocytes in humans during malaria infection. Elife. 2019 Oct 29;8:e49058. PMID: 31658944

7. Collins KA, Wang CY, Adams M, Mitchell H, Rampton M, Elliott S, Reuling IJ, Bousema T, Sauerwein R, Chalon S, Mohrle JJ, McCarthy JS. A controlled human malaria infection model enabling evaluation of transmission-blocking interventions. J Clin Invest. 2018;128(4):1551-62. PMID: 29389671

8. Rutledge GG, Bohme U, Sanders M, Reid AJ, Cotton JA, Maiga-Ascofare O, Djimde AA, Apinjoh TO, Amenga-Etego L, Manske M, Barnwell JW, Renaud F, Ollomo B, Prugnolle F, Anstey NM, Auburn S, Price RN, McCarthy JS, Kwiatkowski DP, Newbold CI, Berriman M, Otto TD. Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution. Nature. 2017;542(7639):101-4. PMID: 28117441

9. Farid R, Dixon MW, Tilley L, McCarthy JS. Initiation of gametocytogenesis at very low parasite density in Plasmodium falciparum infection. J Infect Dis. 2017;215(7):1167-74. PMID: 28498997

Lab research projects

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