van Dooren Group - Cell biology and metabolism of apicomplexan parasites

van Dooren Group Retreat - Mt. Kosciuszko

Apicomplexa are intracellular parasites that severely impact human health and economic prosperity in Australia and around the world. They include the malaria-causing parasite Plasmodium and the opportunistic pathogen Toxoplasma gondii. Our focus is predominantly on Toxoplasma, since the types of questions we are addressing are usually easiest to answer in this organism, although we collaborate extensively with the highly integrated malaria research community at ANU to translate our studies into Plasmodium parasites.

The objective of the ANU Toxo lab is to gain a better understanding of how apicomplexans acquire nutrients from the host cells in which they reside, and how they then convert these nutrients into the molecular building blocks the parasites need to proliferate. We are interested in identifying and characterising compounds that inhibit these processes, with a view to developing new treatment options against these formidable foes. Independently-minded, hard-working students interested in joining our group should contact Giel van Dooren. Students will gain experience in diverse and cutting-edge molecular, physiological and cell biological approaches for studying parasite biology, as well as receiving training in data analysis and scientific writing. We will be recruiting two research officers/assistants to our group as part of NHMRC- and ARC-funded research projects in early 2020. Contact Giel van Dooren for more details.

The lab currently studies three major areas of apicomplexan biology:

  • Nutrient acquisition: How do apicomplexan parasites steal nutrients from the host cells in which they reside? We focus on the role that plasma membrane-localised solute transporters play in these processes. We utilise the facile genetics of Toxoplasma to uncover essential transporters, and then use a broad range of physiological, biochemical, metabolomic, imaging, and heterologous expression approaches to elucidate the function(s) of these transporters. Increasingly, we are becoming interested in how nutrient acquisition changes in the different tissues and organs that parasites inhabit across the course of an infection. To examine these processes we use in vivo mouse infection models. We are in a terrific research environment to characterise the functions of novel transporters, and collaborate extensively with the groups of Kiaran Kirk and Adele Lehane on these projects.
  • Mitochondrial biology: What roles do parasite mitochondria play in proliferation and virulence of these pathogens? We are interested in novel features of the mitochondrial electron transport chain, which is a major drug target in apicomplexans, including in identifying and characterising novel inhibitors of this pathway. We are also interested in how mitochondrial metabolism is integrated into the broader metabolism of these parasites, including in the metabolic relationships between the mitochondrion and apicoplast (a reduced, chloroplast-derived organelle) of these parasites. Our studies in this area use a broad range of physiological, biochemical and cell biological approaches to study mitochondrial biology in both Toxoplasma and Plasmodium, the latter studies conducted in collaborations with Alex Maier and Kevin Saliba.
  • The life cycle of Toxoplasma parasites: The sexual stages of the Toxoplasma life cycle occur exclusively in felids. In close collaboration with visiting professor Nick Smith from the University Technology Sydney, we are interested in understanding the genes and processes that are required for parasites to complete their life cycles in their felid hosts. We use modern genetic, in vitro and in vivo infection approaches to study sexual stage biology of Toxoplasma.

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Selected publications

Rajendran E, Clark M, Goulart C, Steinhöfel B, Tjhin ET, Gross S, Smith NC, Kirk K, van Dooren GG (2021) Substate-mediated regulation of the arginine transporter of Toxoplasma gondii. PLoS Pathog 17(8): e1009816.

Hayward JA, Rajendran E, Zwahlen SM, Faou P, van Dooren GG (2021) Divergent features of the coenzyme Q:cytochyrome c oxidoreductase complex in Toxoplasma gondii parasites. PLoS Pathog 17(2): e1009211.

Fairweather SJ, Rajendran E, Blume M, Javed K, Steinhöfel B, McConville MJ, Kirk K, Bröer S, van Dooren GG (2021) Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii. PLoS Pathog 17(8): e1009835.

Tjhin ET, Howieson VM, Spry C, van Dooren GG, Saliba KJ (2021) A novel heteromeric pantothenate kinase complex in apicomplexan parasites. PLoS Pathog 17(7): e1009797.

Aw YTV, Seidi A, Hayward JA, Lee J, Makota FV, Rug M, van Dooren GG (2021) A key cytosolic iron-sulfur cluster synthesis protein localizes to the mitochondrion of Toxoplasma gondii. Mol Microbiol 115(5): 968-985.

Smith NC, Goulart C, Hayward JA, Kupz A, Miller CM, van Dooren GG (2021) Control of human toxoplasmosis. Int J Parasitol 51(2-3): 95-121.

Tjhin ET, Hayward JA, McFadden GI and van Dooren GG (2020) Characterization of the apicoplast-localized enzyme TgUroD in Toxoplasma gondii reveals a key role of the apicoplast in heme biosynthesis. J Biol Chem 295(6): 1539-50.

Parker KER, Fairweather SJ, Rajendran E, Blume M, McConville MJ, Bröer S, Kirk K and van Dooren GG (2019) The tyrosine transporter of Toxoplasma gondii is a member of the newly defined apicomplexan amino acid transporter (ApiAT) family. PLoS Pathogens 15(2): e1007577.

Lehane AM, Dennis ASM, Bray KO, Li D, Rajendran E, McCoy JM, McArthur HM, Winterberg M, Rahimi F, Tonkin CJ, Kirk K and van Dooren GG (2019) Characterization of the ATP4 ion pump in Toxoplasma gondii. J Biol Chem 294(14): 5720-34.

Seidi A, Muellner-Wong LS, Rajendran E, Tjhin ET, Dagley LF, Aw VY, Faou P, Well AI, Tonkin CJ and van Dooren GG (2018) Elucidating the mitochondrial proteome of Toxoplasma gondii reveals the presence of a divergent cytochrome c oxidase. eLife e38131.

Rajendran E, Hapuarachchi SV, Miller CM, Fairweather SJ, Cai Y, Smith NC, Cockburn IA, Bröer S, Kirk K and van Dooren GG (2017) Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites. Nature Commun 8: 14455.

Brooks CF§, Johnsen H§, van Dooren GG§, Muthalagi M, Lin SS, Bohne W, Fischer K and Striepen B (2010) The Toxoplasma apicoplast phosphate translocator links cytosolic and apicoplast metabolism and is essential for parasite survival. Cell Host Microbe 7(1): 62-73. §contributed equally

van Dooren GG, Reiff SB, Tomova C, Meissner M, Humbel BM, Striepen B (2009) A novel dynamin-related protein has been recruited for apicoplast fission in Toxoplasma gondii. Curr Biol 19(4): 267-276.

van Dooren GG, Tomova C, Agrawal S, Humbel BM, Striepen B (2008) Toxoplasma gondii Tic20 is essential for apicoplast protein import. Proc Natl Acad Sci USA, 105(36): 13574-13579.

Chtanova T, Schaeffer M, Han SJ, van Dooren GG, Nollmann M, Herzmark P, Chan SW, Satija H, Camfield K, Aaron H, Striepen B, Robey EA (2008) Dynamics of neutrophil migration in lymph nodes during infection. Immunity 29(3): 487-496.

van Dooren GG, Marti M, Tonkin CJ, Stimmler LM, Cowman AF, McFadden GI (2005) Development of the endoplasmic reticulum, mitochondrion and apicoplast during the asexual life cycle of Plasmodium falciparum. Mol Microbiol 57(2): 405-419.

Ralph SA, van Dooren GG, Waller RF, Crawford MJ, Fraunholz MJ, Foth BJ, Tonkin CJ, Roos DS, McFadden GI. (2004) Metabolic maps and functions of the Plasmodium falciparum apicoplast. Nat Rev Microbiol 2(3): 203-16.

All publications

Toxoplasma gondii

Truth or Myth: Toxoplasma as a behavioural disturber

Story | Tuesday 11 August 2020
Studies have shown that some parasites can control their hosts, manipulating their behaviour often to the benefit of the parasites.
By Forest & Kim Starr, CC BY 3.0 us,

If only invasive species were taking their parasites in their luggage

Story | Tuesday 11 August 2020
Jeremy Debrulle discusses (Torchin et al. 2003) and the question of what role do parasites actually play in regulating and stabilising populations?
Linden Muellner-Wong received her RSB Director's Prize in Honours award from RSB Director, Allen Rodrigo. Image Sharyn Wragg.

Linden Muellner-Wong awarded RSB Director's Prize in Honours

Story | Tuesday 13 February 2018
Linden Muellner-Wong has won a 2017 RSB Director's Prize in Honours.

January was a busy month for outreach

Story | Monday 30 January 2017
January is not normally thought of as a teaching-heavy month, but RSB members were involved in a number of outreach events early this year.

'Concepts in Parasitology' at ANU Canberra and Kioloa Coastal Campus

Story | Thursday 18 December 2014
The future of parasite research in Australia will be in safe hands as 16 young Australian scientists converged for an intensive 2-week workshop with world-leading biologists to study worms, protozoans, ticks, fleas, lice and more.

ARC Discovery projects and DECRA fellowships

Story | Monday 17 November 2014

ARC grant success

Story | Thursday 3 November 2011

BSB PhD Exit Seminar: Elucidating and exploiting the mitochondrial electron transport chain of T. gondii parasites

Event | Thu 17 February 2022
As you read this abstract, your lungs are (I hope!) bringing live-sustaining oxygen into your body. Oxygen is required by our cells for one key purpose – to act as the final electron acceptor in the mitochondrial electron transport chain (ETC).

Characterising putative transporter proteins in apicomplexan parasites identifies one that is critical for Toxoplasma gondii invasion

Event | Thu 5 March 2020
PhD exit seminar by Sanduni Hapuarachchi from the van Dooren Group at the Research School of Biology, whose work highlights the important roles transporters play in parasites and open avenues to further explore this important class of proteins.

Feeling hot in here: thermotolerance and drug sensitivity in malaria parasites

Event | Fri 28 February 2020
Audrey Odom John, Chief of the Division of Infectious Diseases at Children’s Hospital of Philadelphia. A physician-scientist, Dr. John’s NIH-funded research has focused on Plasmodium falciparum malaria parasites, with a particular interest in targeting parasite metabolism to identify novel targets for drug development