The Walter and Eliza Hall Institute of Medical Research

Dr Jake Baum

Details

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Division: Infection & Immunity

Research Overview

Throughout its complex lifecycle the malaria parasite must traverse tissues and invade a diversity of host cells to ensure successful propagation of the lifecycle. However, malaria parasites don’t depend on a flagellum to move, nor do they use arp2/3-mediated membrane protrusions (indeed they entirely lack the arp2/3 complex and its regulators). Instead, malaria parasites utilise a unique actin-myosin motor that enables them to literally glide across cell surfaces and enter host cells. The components of this gliding motor are well established yet we still know almost nothing about how motility is regulated. The Baum lab is focused on understanding the regulation of this motor, in particular actin – the molecular clutch at the heart of gliding motility. Our research uses a combination of genetics, biochemistry and the latest tools in fluorescence microscopy and live-imaging, to understand the cell biology of motility, which, given its unique nature, should provide a target for novel antimalarials that prevent cell movement and thereby stop malaria disease.

Research Projects

The mechanics of malaria parasite invasion of the human erythrocyte

Actin regulation in the malaria parasite

Cytoskeletal dynamics across the malaria parasite lifecycle

Major Publications

1. Baum J, Papenfuss AT, Mair GR, Janse CJ, Vlachou D, Waters AP, Cowman AF, Crabb BS, de Koning-Ward TF.
   Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites.
   Nucleic Acids Res. 2009 Jun;37(11):3788-98. Epub 2009 Apr 20. PMID: 19380379 [PubMed - indexed for MEDLINE]
2. Maier AG, Baum J, Smith B, Conway DJ, Cowman AF.
   Polymorphisms in erythrocyte binding antigens 140 and 181 affect function and binding but not receptor specificity in Plasmodium falciparum.
   Infect Immun. 2009 Apr;77(4):1689-99. Epub 2009 Feb 9. PMID: 19204093 [PubMed - indexed for MEDLINE]
3. Baum J, Chen L, Healer J, Lopaticki S, Boyle M, Triglia T, Ehlgen F, Ralph SA, Beeson JG, Cowman AF.
   Reticulocyte-binding protein homologue 5 - an essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum.
   Int J Parasitol. 2009 Feb;39(3):371-80
   PMID: 19000690 [PubMed - in process]
4. Baum J, Gilberger TW, Frischknecht F, Meissner M.
   Host-cell invasion by malaria parasites: insights from Plasmodium and Toxoplasma.
   Trends Parasitol. 2008 Dec;24(12):557-63
   PMID: 18835222 [PubMed - in process]
5. 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 - indexed for MEDLINE]
6. 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]
7. Baum J, Maier AG, Good RT, Simpson KM, Cowman AF.
   Invasion by P. falciparum merozoites suggests a hierarchy of molecular interactions.
   PLoS Pathog. 2005 Dec;1(4):e37
   PMID: 16362075 [PubMed - indexed for MEDLINE]
8. Baum J, Richard D, Healer J, Rug M, Krnajski Z, Gilberger TW, Green JL, Holder AA, Cowman AF.
   A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites.
   J Biol Chem. 2006 Feb 24;281(8):5197-208
   PMID: 16321976 [PubMed - indexed for MEDLINE]
9. Marti M, Baum J, Rug M, Tilley L, Cowman AF.
   Signal-mediated export of proteins from the malaria parasite to the host erythrocyte.
   J Cell Biol. 2005 Nov 21;171(4):587-92
   PMID: 16301328 [PubMed - indexed for MEDLINE]
10. Simpson KM, Baum J, Good RT, Winzeler EA, Cowman AF, Speed TP.
    A comparison of match-only algorithms for the analysis of Plasmodium falciparum oligonucleotide arrays.
    Int J Parasitol. 2005 Apr 30;35(5):523-31
    PMID: 15826644 [PubMed - indexed for MEDLINE]

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Current Laboratory Members

Faculty Member: Jake Baum, BA(Hons) MA Oxon MSc PhD London

Research Assistant: Fiona Angrisano, BBiolSc(Hons) LaT

Research Assistant: Danushka Marapana BSc(Hons) Melb

Postgraduate Student: David Riglar, BSc(Hons) Melb

Postgraduate Student: Liz Zuccala, BSc Melb

Visiting Scientist: Eleanor Hamlyn, MD London