Project Reference: TRG27-BIO-RW1
Project title: Unveiling the protein trafficking machinery from the ER to relict plastid of apicomplexan parasites
Project outline
One of the most unexpected discoveries in malaria research is that the causative agents, Plasmodium spp., contain a non-photosynthetic plastid organelle (i.e. a colourless chloroplast). This organelle persists in most parasites of the phylum Apicomplexa, including the prolific human parasite Toxoplasma gondii. Even more remarkable, these plastids reside within the cell’s endomembrane system and are separated from the cytoplasm by four membranes in total. Most plastid proteins are encoded in the nucleus, so new proteins take a convoluted route to their plastid destinations. First, they are imported into the ER. From here they must be discriminated from proteins destined to other endomembrane or secretory compartments and packaged into vesicles directed to the plastid. Vesicle fusion with the outer plastid membrane leaves three more membranes to cross, and dedicated translocons occur in each.
We have discovered molecular components of each of these trafficking steps using Toxoplasma as a model. Each step has involved rewiring existing machineries and processes, with a common theme being the repurposing of misfolded protein recognition and elimination processes. The aims of this project are to answer the questions:
- How has the molecular composition of these sorting machineries changed with their new functions of plastid trafficking?
- How do their components contribute to this new function?
- How do the existing processes of ER protein quality control distinguish misfolded ER proteins from those for plastid delivery?
To answer these questions this project will use: protein complexome biology and mass spectrometry; gene knock-outs/downs, advanced microscopy methods and protein targeting assays to test function; and phylogenomic profiling to understand the evolution of these targeting machineries throughout Apicomplexa.
Plastid function is essential to Plasmodium and Toxoplasma and understanding its biology offers promise for novel therapeutic strategies.
Principal Supervisor
Professor Ross Waller
Email address: rfw26@cam.ac.uk
Department / Partner Institute: Biochemistry
Website: http://www.wallercellevolution.com
BBSRC strategic theme
Understanding the rules of life