Trypanosomatidae are a widespread group of flagellated protozoa that cause highly disabling, often fatal, diseases and economic losses in endemic countries. Distinct Trypanosomatidae, transmitted by specific arthropod vectors, can cause human diseases: Trypanosoma (T) brucei (sleeping sickness), T. cruzi (Chagas’ disease), and Leishmania spp (leishmaniases). A related disease caused by T. vivax, T. congolense and T. brucei called nagana decimates livestock in Africa and more recently in South America. The small size of these eukaryotic parasites and the spatial resolution limits of conventional imaging technologies have hampered analysis of host-parasite interactions at the single cell level. We have previously established and validated innovative imaging technologies to visualize tissue localization dynamics of Leishmania and Trypanosoma in vertebrate hosts. We propose to build upon our complementary expertise in cutting edge imaging and cellular host interactions to develop and use bioluminescence/fluorescence quantitative imaging with 2D and 3D spatial resolution. The major scope of our “Tryp Imaging” PTR is i) to establish and optimize new bright bioluminescent and far red fluorescent transgenic parasites, ii) to develop quantitative monitoring of parasite burden in real time and iii) to monitor disease progression by examining host-parasite interactions over time and in the three-dimensional space of living hosts. These quantitative imaging studies will open up possibilities to analyze infectious processes in real time by monitoring in vivo the parasite size populations. Additionally, the investigation of the cellular mechanisms at the host and tissue levels with high temporal and/or spatial resolution allows the further elucidation of the dynamics of intracellular trafficking events. The resulting data obtained at the end of this project will greatly enhance our understanding of leishmaniasis and trypanosomiasis pathogenic process, and will provide a major breakthrough in anti-parasitic research.
Area of special interest / keywords: Trypanosomatidae, Leishmania, Trypanosoma, transgenic parasites, 2D-3D real time imaging, bioluminescence/fluorescence intravital imaging, mammalian host
Experimental rodent models: ex vivo/in vivo /in situ