Our laboratory works predominantly on Plasmodium falciparum the causative agent of the most severe form of malaria in humans. This disease causes millions of deaths and much suffering in people living in tropical and subtropical regions of the world. Our main aim is to understand how this parasite infect humans and the mechanisms it uses to evade host immune responses as this knowledge is critical in identifying and designing new treatments and vaccines that are urgently required for this disease.

The development of a vaccine is a priority, and potential vaccines are being targeted to various stages of the parasite life cycle. The asexual merozoite has been of particular focus in recent times. The merozoite form of the asexual life cycle in the blood-stage attaches to the surface of the red blood cell thus initiating the invasion process of this host cell. Inside the red blood cell the parasite replicates and matures into a schizont form, which eventually ruptures to release new merozoites and complete the blood-stage cycle. Merozoite antigens are exposed to the immune system and consequently these proteins are potential vaccine candidates. Many of these proteins are thought to play a role in merozoite invasion of red blood cells but the details of their function remain sketchy at best. Our work is aimed at identifying and determining the role of merozoite proteins and specific red blood cell receptors in the invasion process. See below for some of our recent publications in this area.

Most of the clinical symptoms and the associated mortality and morbidity of falciparum malaria are a result of the parasite undergoing continuous cycles of asexual reproduction within human red blood cells. Infected red blood cells become rigid, poorly deformable, and develop the ability to cytoadhere to a number of cell types such as vascular endothelial cells, a mechanism that prevents the parasitised host cells from passing through to the spleen where they would be cleared from the blood stream. These cellular modifications of the infected red blood cell are the result of a dramatic remodelling process induced by the parasite that ultimately serves to induce cytoadherence by exposing various ligands on the erythrocyte surface for host cell receptors and facilitate nutrient import into the infecting parasite. Our work is aimed at understanding the role of proteins in this remodelling process and cytoadherence of the infected erythrocyte as this is pivotal to the successful infection of the erythrocyte by this parasite and pathogenesis of the disease. See below for some of our recent publications in this area.

The malaria parasite P. falciparum undergoes antigenic variation to evade host immune responses through switching expression of variant surface proteins encoded by the var gene family. There are approximately 60 var genes in each P .falciparum genome and they encode the erythrocyte membrane protein 1 (PfEMP1). PfEMP1 is expressed at the surface of infected erythrocytes and mediates binding to receptors on host cells. To avoid clearance by anti-PfEMP1 antibodies, P. falciparum can change the variant form of PfEMP1 expressed on the erythrocyte by activating a different var gene in the genome. This process of antigenic variation underpins the chronicity and virulence of this parasite and our work is aimed at understanding the regulation of var gene silencing and activation. See below for some of our recent publications in this area.

Jake Baum, Senior Postdoctoral Fellow
Rachel Lundie, Research Officer
Fiona Angrisano, Research Assistant
David Riglar, BSc Honours Student

Dr Alexander Maier, Senior Postdoctoral Fellow
Dr Julie Healer, Project Manager
Dr Alex Uboldi, Postdoctoral Fellow
Monica Brown, Research Assistant
Ping Cannon, Research Assistant
Matthew O'Neill, Research Assistant
Thuan Phuong, Research Assistant
Jennifer Thompson, Research Assistant

1. Baum J, Tonkin CJ, Paul AS, Rug M, Smith BJ, Gould SB, Richard D, Pollard TD, Cowman AF.

A malaria parasite formin regulates actin polymerization and localizes to the parasite-erythrocyte moving junction during invasion.

Cell Host Microbe . 2008 Mar 13;3(3):188-98

PMID: 18329618 [PubMed - in process]

2. Voss TS, Tonkin CJ, Marty AJ, Thompson JK, Healer J, Crabb BS, Cowman AF.

Alterations in local chromatin environment are involved in silencing and activation of subtelomeric var genes in Plasmodium falciparum.

Mol Microbiol . 2007 Oct;66(1):139-50

PMID: 17725559 [PubMed - indexed for MEDLINE]

3. Maier AG, Rug M, O'Neill MT, Beeson JG, Marti M, Reeder J, Cowman AF.

Skeleton-binding protein 1 functions at the parasitophorous vacuole membrane to traffic PfEMP1 to the Plasmodium falciparum-infected erythrocyte surface.

Blood . 2007 Feb 1;109(3):1289-97

PMID: 17023587 [PubMed - indexed for MEDLINE]

4. Baum J, Papenfuss AT, Baum B, Speed TP, Cowman AF.

Regulation of apicomplexan actin-based motility.

Nat Rev Microbiol. 2006 Aug;4(8):621-8

PMID: 16845432 [PubMed - indexed for MEDLINE]

5. Rug M, Prescott SW, Fernandez KM, Cooke BM, Cowman AF.

The role of KAHRP domains in knob formation and cytoadherence of P falciparum-infected human erythrocytes.

Blood. 2006 Jul 1;108(1):370-8

PMID: 16507777 [PubMed - indexed for MEDLINE]

6. Sargeant TJ, Marti M, Caler E, Carlton JM, Simpson K, Speed TP, Cowman AF.

Lineage-specific expansion of proteins exported to erythrocytes in malaria parasites.

Genome Biol. 2006;7(2):R12

PMID: 16507167 [PubMed - indexed for MEDLINE]

7. Cowman AF, Crabb BS.

Invasion of red blood cells by malaria parasites.

Cell. 2006 Feb 24;124(4):755-66

PMID: 16497586 [PubMed - indexed for MEDLINE]

8. Voss TS, Healer J, Marty AJ, Duffy MF, Thompson JK, Beeson JG, Reeder JC, Crabb BS, Cowman AF.

A var gene promoter controls allelic exclusion of virulence genes in Plasmodium falciparum malaria.

Nature. 2006 Feb 23;439(7079):1004-8

PMID: 16382237 [PubMed - indexed for MEDLINE]

9. Stubbs J, Simpson KM, Triglia T, Plouffe D, Tonkin CJ, Duraisingh MT, Maier AG, Winzeler EA, Cowman AF.

Molecular mechanism for switching of P. falciparum invasion pathways into human erythrocytes.

Science. 2005 Aug 26;309(5739):1384-7

PMID: 16123303 [PubMed - indexed for MEDLINE]

10. Knuepfer E, Rug M, Klonis N, Tilley L, Cowman AF.

Trafficking of the major virulence factor to the surface of transfected P.

falciparum-infected erythrocytes. Blood

PMID: 15692070 [PubMed - indexed for MEDLINE]

11. Duraisingh MT, Voss TS, Marty AJ, Duffy MF, Good RT, Thompson JK, Freitas-Junior LH, Scherf A, Crabb BS, Cowman AF.

Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium falciparum.

Cell. 2005 Apr 8;121(1):13-24

PMID: 15820675 [PubMed - indexed for MEDLINE]

12. Marti M, Good RT, Rug M, Knuepfer E, Cowman AF.

Targeting malaria virulence and remodeling proteins to the host erythrocyte.

Science. 2004 Dec 10;306(5703):1930-3

PMID: 15591202 [PubMed - indexed for MEDLINE]

13. Maier AG, Duraisingh MT, Reeder JC, Patel SS, Kazura JW, Zimmerman PA, Cowman AF.

Plasmodium falciparum erythrocyte invasion through glycophorin C and selection for Gerbich negativity in human populations.

Nat Med. 2003 Jan;9(1):87-92

PMID: 12469115 [PubMed - indexed for MEDLINE]

Faculty Member:	Alan Cowman, BSc(Hons) Griffith FAA PhD Melb
Senior Postdoctoral Fellow:	Jake Baum, BA(Hons) MA Oxon MSc PhD London
Postdoctoral Fellow:	Justin Boddey, BBiomedSc(Hons) PhD Griffith
Senior Postdoctoral Fellow:	Lin Chen, PhD LaT
Postdoctoral Fellow:	Svenja Gunther, PhD Glasgow
Senior Postdoctoral Fellow:	Julie Healer, BSc(Hons) Glasgow M.Phil London PhD Edinburgh
Senior Postdoctoral Fellow:	Alexander Maier, BSc Southern Colorado Dipl. Biol. Tuebingen PhD Heidelberg
Postdoctoral Fellow:	Thomas Nebl, PhD LaT
Postdoctoral Fellow:	Andrew Pearce, BSc(Hons) ANU PhD Melb
Postdoctoral Fellow:	Dave Richard, PhD Laval
Senior Postdoctoral Fellow:	Melanie Rug, PhD Heidelberg
Senior Postdoctoral Fellow:	Wai-Hong Tham, BA California PhD Princeton
Senior Postdoctoral Fellow:	Chris Tonkin, BSc(Hons) PhD Melb
Senior Postdoctoral Fellow:	Tony Triglia, BSc(Hons) MSc Melb
Senior Postdoctoral Fellow:	Alex Uboldi, BSc(Hons) PhD Witwatersrand
Postdoctoral Fellow:	Jennifer Volz, MSc Humboldt PhD EMBL
Research Assistant:	Monica Brown
Research Assistant:	Ping Cannon, BSc Shanghai
Research Assistant:	Christine Langer
Research Assistant:	Sash Lopaticki, BSc(Hons) VUT
Research Assistant:	Matthew O'Neill, BSc(Hons) Melb
Research Assistant:	Thuan Phuong, BSc(Hons) LaT
Research Assistant:	Jennifer Thompson, MSc Melb
Undergraduate Student:	David Riglar, BSc Melb
Research Assistant:	Fiona Angrisano, BBiolSc(Hons) LaT

Some Previous Laboratory Members		Current Affiliation
Justin Rubio	1992-1996	Howard Florey Institute (Laboratory Head)
Brendan Crabb	1995-1997	Director, Burnet Institute
Mark Wickham	1996-2003	Phillips Ormonde & Fitzpatrick, Patent Attorneys
Michael Reed	1998-2001	McGill University, Canada (Assistant Professor)
Deborah Baldi	1998-2001	University of Melbourne (Postdoctoral Fellow)
Manoj Duraisingh	1998-2003	Harvard University (Assistant Professor)
Tim-Wolf Gilberger	1999-2004	Bernard Nocht Institute of Tropical Medicine, Germany (Laboratory Head)
Till Voss	2002-2006	Swiss Tropical Institute (Professor)
Matthias Marti	2003-2006	Harvard University (Assistant Professor)
Stuart Ralph	2005-2007	Bio21, University of Melbourne (Group Leader)