A comparative proteomic approach to identify and validate African trypanosome proteins at the host-parasite interface

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Parasitic diseases afflict many of the world?s population, and the majority of people on our planet at at risk from one or several such agents. The diseases these parasites cause range from malaria to gut, skin and organ infections. In Africa, the trypanosome parasite is responsible for much death and morbidity - infection is brought about when an infected tsetse fly takes a blood meal. Without treatment the infected person will progress through general ill health symptoms to multiple organ malfunction, coma and death. Related trypanosomes also cause disease in Asia, South America, the Middle East and Southern Europe.Due to a remarkable system where the African trypanosome changes its coat at regular intervals, the host immune system is unable to control the parasite, which results in efficient infection and invariably death if untreated. Vaccines are unlikely due to the varying coat, and the drugs in use at over 50 years old, frequently toxic and failing due to emergence of resistance. Urgent new research is needed to identify potential new therapeutic options and diagnostics. One aspect of the parasite that is unique is a region of the surface where all molecules that form the coat emerge when they are made, called the flagellar pocket. As the surface is the boundary between host and parasite, understanding how this is maintained is of major scientific interest as well as of practical utility in uncovering new ways in which the trypanosome may be vulnerable to drug treatments. We wish to find out what proteins are present in the flagellar pocket, with the expectation that an understanding of the molecules that are present will provide insights into how the pocket performs its job. There has so far been limited success with defining the flagellar pocket, and we propose a method that requires considerable computer power and wide-raging analysis as a solution to the problem. Most importantly, following on from the identification of candidate flagellar pocket proteins, we will look to see which expected proteins have been identified, and also, in combination with computer predictions, will localize a range of unknown proteins using the jellyfish green fluorescent protein, or GFP. This will allow us to assess how many of the proteins really are parts of the flagellar pocket, and hence begin to understand how this organelle contributes to the ability of the trypanosome to cause disease.