Grant: Project Grant

Kinetoplastid parasites affect millions of people each year worldwide, with an increasing number of cases in North America and Europe. These parasites are transmitted by insect bites and affect humans and animals. They include three main species of medical importance: Trypanosoma brucei, T. cruzi, and Leishmania sp., which cause Sleeping sickness in Africa, Chagas disease in the Americas, and Leishmaniasis in multiple countries, respectively. These parasites cause fatal chronic illnesses that affect numerous organs, including the brain, heart, spleen, and skin, depending on parasite species. It remains unknown how these parasites escape the human immune response during infection. This project focuses on how T. brucei avoid host antibody recognition during infection. T. brucei express a surface coat made by a protein called variant surface glycoprotein (VSG), which they periodically change to escape host antibody recognition in a process known as antigenic variation. The processes that control the periodic change in the VSG surface coat are poorly understood. We have discovered that T. brucei use a signalling system to control changes in the VSG coat. This proposal will investigate the protein composition of this signalling system, its organization within the parasite, and how it controls the periodic changes in VSG proteins. Understanding this system will help to identify drugs that can disrupt the parasite's ability to change the VSG coat, which will result in parasite elimination by the host immune system during infection. Many other parasites use similar processes to escape the host immune system, such as Plasmodium spp., which cause malaria and Giardia spp., which cause intestinal infections. Hence, understanding the processes that control antigenic variation in T. brucei may also help to fight other pathogen infections.