PI: Jayne Raper (Hunter College of the City of New York University)
CoPIs: Jose Cibelli (Michigan State University); Alan Archibald (University of Edinburgh); Steve Kemp, International Livestock Research Institute (ILRI) (Nairobi, Kenya)
Collaborators: Aris Economides (Regeneron Pharmaceuticals); Bruce Whitelaw (University of Edinburgh)
Trypanosomiasis affects cattle and is prevalent in 36 countries of sub-Saharan Africa. It is caused by parasites of the Trypanosoma species, which are transmitted by tsetse flies. Infection with these parasites invariably leads to death. In addition cattle are reservoirs for trypanosomes that infect humans and thereby cause an increase in disease transmission resulting in human sleeping sickness, which is also fatal. Baboons are naturally resistant to all these pathogens due to a factor in their blood known as trypanosome lytic factor, which is a form of High-Density Lipoprotein (the "good" cholesterol). A single baboon gene has been identified that when given transiently to mice by gene therapy (as mice do not have this gene), completely protects them from infection with trypanosomes. The goal of this research project is to determine if the mechanism of species-specific trypanosome resistance characterized in primates is shared by other vertebrates, such as cattle.
Broader Impacts: Trypanosomiasis is arguably one of the most significant diseases to threaten livestock production in infected areas of the world. The animal disease causes immense human suffering due to the reduction of milk and meat production by approximately 50%, as well as the lack of haulage for crop production, which are central to most African small scale agriculture. Accordingly, trypanosomiasis is ranked among the top 10 global cattle diseases impacting on the poor, and estimates of the cost of the disease to livestock keepers and consumers vary between $1 to 5 billion US dollars annually. This research project could lead to improved sustainability of livestock production in a broad region of the developing world. Drugs that kill trypanosomes have been extensively used in animals (35 million doses/year), but drug resistance and disease resurgence has been reported in at least 13 countries. If this basic research project could demonstrate the proof of principle that cattle with the baboon gene have complete protection from all pathogenic African trypanosomes, including human infective trypanosomes, it could have a strong long term impact in that it could lead to the elimination of an important reservoir that drives human infection. Public access to data and biological materials generated by this research project will be available through a project wiki - www.genomics.liv.ac.uk/tryps/index.php.
