Chris Tonkin-Projects

Chris Tonkin-Projects

Projects

How do apicomplexan parasites activate motility and invasion?

Upon the right environmental cues Toxoplasma and Plasmodium parasites activate motility and host cell invasion. How they undertake this process is ill defined. Indeed, signal transduction pathways are important drug targets for a range of diseases and therefore have great promise for the development of new anti-parasitic agents.  Intracellular Ca2+ flux is required for activation of motility and we and others have determined an important role for a group of ‘plant-like’ calcium-dependent protein kinases (CDPKs) in translating Ca2+ flux into an enzyme activity. We use powerful forward and reverse molecular genetic techniques, together with quantitative proteomics and live cell imaging to understand the role of particular molecules and define their action in activating egress motility and invasion.

 

 

 

 

 

 

How do Apicomplexan parasites move?

Apicomplexan parasites such as Plasmodium and Toxoplasma use a unique form of motility to power host cell invasion and egress as well as tissue dissemination. Given that these processes are essential for pararasite pathogenesis understanding how they create force is important. Molecular genetic studies have demonstrated that the ‘glideosome’ is important for parasite motility and consists of a myosin anchored to the parasite periphery by the glideosome associated protein (GAP) complex. The myosin is made up of a unusual ‘type XIV’ myosin, MyoA complexed with two light chains. We are interested in defining how the myosin produces force to drive motility and how the glideosome is linked to the adhesins which bind to the host cell. Here we are using a combination of structural biology, parasite molecular biology and biophysics to understand how force is produced to drive apicomplexan motility.