Ross Waller

Ross Waller

University of Cambridge

Completed a PhD the University of Melbourne with postdocs at both Melbourne and the University of British Columbia. Returned to a faculty position at the University of Melbourne (2005) and then relocated his lab to the University of Cambridge in 2014. His lab is studying key evolutionary processes and transitions that have led to cell diversity, with particular focus on adaptations for symbiotic interactions.

A subcellular atlas of Toxoplasma reveals the functional and evolutionary context of the proteome

Apicomplexans are human and animal protozoan pathogens responsible for diseases including malaria, cryptosporidiosis and toxoplasmosis. As obligate intracellular parasites they are highly organised cells with numerous novel and specialised sub-compartments that form the basis of their invasion biology, host defence evasion, and novel metabolic traits. However, our understanding of these cells is highly constrained by our limited knowledge of the locations and functions of most of the cell’s proteome. Even in the best-studied apicomplexans (Plasmodium and Toxoplasma) only a small fraction of proteins’ locations has been experimentally determined, with most assignments based on predictions from orthologues in distant relatives. Moreover, many parasite proteins are annotated as ‘hypotheticals’, for example 4113 of 8121 Toxoplasma proteins, and many are unique to parasites stymying even predictions of location or function by comparative biology. To address this deficit in our basic understanding of the compositional organisation of the apicomplexan cell, we have used a spatial proteomics method called hyperLOPIT to simultaneously capture the steady-state subcellular association of thousands of proteins in the apicomplexan Toxoplasma. These protein atlases reveal: the landscapes of conservation and novelty of cell compartments through evolutionary time; contemporary differences of selective pressures across the different cell compartments; clear instances of protein relocation from one organelle to a different one during apicomplexan speciation; and presence of cell structures otherwise thought lost. This new, global view of the organisation of the apicomplexan cell proteome provides a much more complete framework for understanding the mechanisms of function, evolution and biology of these cells.