Nutrient Uptake and Metabolism - Project A4

Characterising solute transporters in apicomplexan parasites

Host labs:  Giel van Dooren, Adele Lehane, Kiaran Kirk (Research School of Biology, ANU, Canberra)

 

Partner lab:  Martin Blume (Robert Koch Institute, Berlin)

 

 

Background: Solute transporters facilitate the transport of nutrients, metabolites and ions across the membranes that enclose cells and their organelles.  Previous studies in our labs have identified a range of solute transporters that we have shown to play key roles in the acquisition of nutrients in apicomplexan parasites. Using Toxoplasma gondii as a model system, we have identified numerous, apicomplexan-specific solute transporters that localise to various cellular membranes and organelles, and which are critical for proliferation of the disease-causing stages of these parasites. However, for many of these transporters the substrate-specificity and physiological functions remain unknown.

 

Scope/Central question: In this project, we will use a range of approaches that build on our existing collaborations1 to characterise the importance and physiological roles of apicomplexan-specific transporters in both T. gondii and Plasmodium falciparum.

 

Methods employed: The student undertaking this project will be trained in cutting-edge genetic (van Dooren lab), metabolomic (Blume lab) and physiological (Lehane/Kirk labs) techniques, and gain insights into fundamental but understudied processes in these parasites.

  

3-year plan:

 

Year 1. Preliminary characterisation of candidate transporters, including the generation of parasite strains in which the expression of                        candidate transporters can be silenced (Canberra)

 

Year 2. Metabolomic analyses of parasite strains, including strains in which candidate transporter expression has been silenced (Berlin)

 

Year 3. Functional characterisation of candidate transporters to reveal their substrates and importance for parasite physiology.

 

 

Keywords: transporter, Toxoplasma, nutrient uptake

Keywords (methods): genome editing, metabolomics, Xenopus oocyte expression

 

References:

1.         Parker, K.E.R. et al. The tyrosine transporter of Toxoplasma gondii is a member of the newly defined apicomplexan amino acid transporter (ApiAT) family. PLoS Pathog 15, e1007577 (2019).