Grant: Alliance Grants

Secretion, the process of sending material outside of the cell, is a critical capacity of all eukaryotic cells and underpins the infectious processes of many parasites, including Giardia intestinalis, more commonly known in Canada as Beaver Fever. Giardia's cell structure is unusual in having specialized, yet poorly understood, compartments at its cell surface interface that do both secretion and material uptake. Moreover, it appears to have swapped some of its components (proteins called clathrin) that normally help with the secretory process with independently evolved replacements. Such proteins are normally quite conserved and found in nearly all eukaryotic cells, though the details of how its structure works and allows for stable function remain open questions. We will use computational and evolutionary approaches, working with our international partners in the UK and Switzerland, to understand the molecular bases of secretion in Giardia and its parasitic and free living relatives. This will not only tell us more about how this parasite works, it will give us insight into the evolutionary process that transformed harmless, mud-dwelling, creatures into prevalent gut parasites. We will also use the unique Giardia clathrin protein as a springboard for a larger evolutionary investigation to identify the specific determinants of how this machinery keeps its structure and function in different types of organisms and cells. Our work will help people to understand the workings of a prominent pathogen of livestock and people, as well as provide deeper understanding of how parasites evolve. At the same time, the work will uncover fundamental aspects of a piece of cellular machinery found in every eukaryotic cell, across animals, parasites, algae and plants.