2705, boulevard Laurier, RC-709
CANADA G1V 4G2
Tel:+1 418-525-4444, local 47608
barbara [dot] papadopoulou [at] crchul [dot] ulaval [dot] ca (Email)
Our main research program aims at identifying and characterizing the factors and the mechanisms involved in the pathogenesis of intracellular parasites. The model system we actually used is the protozoan parasite Leishmania. Pathogenic Leishmania species cause a diverse group of diseases, collectively called leishmaniasis, that range in severity from spontaneously healing skin ulcers to fatal visceral disease. Leishmania are intracellular parasites, which reside almost exclusively within mononuclear phagocytes of the mammalian host. There are two developmental forms of Leishmania, the motile promastigote transmitted to humans by the sand fly and the non-motile amastigote in the vertebrate host. The ability of Leishmania amastigotes to surviving in the adverse milieu of the phagolysosome and evading the defense mechanisms induced by the host is the key to the successful infection mounted by this pathogen. Genes preferentially expressed in response to various intracellular stimuli should play a central role in parasite's survival within the host cell. As part of the ongoing work in my laboratory, which is funded mainly by CIHR and Burroughs Wellcome Fund, we have initiated studies on the identification of genes specifically expressed in Leishmania's intracellular stage. Novel genes and mechanisms related to stage-specific expression were identified. Our main research interest is to assess the function of genes and/or proteins that are predominantly expressed upon macrophage infection and to delineate the molecular mechanisms, which control their stage-specific expression and contribute to parasite pathogenesis. We propose to use a global strategy based on a combination of genomics (DNA microarrays) and proteomics studies to isolate genes/proteins predominantly expressed upon contact or growth within the host cell. Our studies are focused on the L. donovani species that are responsible for the most severe form of the disease, the visceral leishmaniasis. The completion of the L. major genomic sequence (September 2003) and the recent initiative for sequencing the L. infantum genome should speed gene identification and allow, within the coming years, the development and use of several functional genomic-related technologies for analyzing the expression and the function of genes upon different intracellular conditions.
The specific objectives of my research program are to:
- Identify genes/proteins of Leishmania donovani infantum that are specifically expressed upon parasite differentiation within the host macrophages
- Investigate the mechanism(s) involved in the regulation of genes specifically expressed in the intracellular stage of the parasite
- Study the function of genes important for parasite intracellular survival
- Develop novel strategies for vaccination against intracellular pathogens
Possible outcomes of the ongoing research program
The identification of genes expressed predominantly upon growth of the parasites in the mammalian host and the study of the mechanism(s) that control their stage-specific regulation are fundamental for our understanding on how intracellular pathogens survive within their host and build an infection. With the progress anticipated in the field of functional genomics and microbe genomic sequencing, we should be in a position to globally address gene/protein expression and function in the L. donovani species, but also to initiate similar studies in other microbial pathogens. Overall, these studies should increase our understanding of the mechanisms controlling the pathogenesis of Leishmania parasites and should eventually lead to the identification of interesting targets for the development of effective vaccines and new drugs.