1) Parasitology, animal pathology: Trypanosoma congolense and trypanosoma vivax, the main causative agent of animal trypanosomiasis in Africa, is an extracellular tsetse fly-transmitted protozoan parasite found in the blood of several mammalian hosts such as cow and rodent.The main pathological features of animal trypanosomiasis are weight loss, anaemia and immunosuppression but the mechanisms involved are poorly understood. Attempts to control trypanosomiasis are mainly based on the use of trypanocidal drugs and on vector control. However, since no new drugs have been developed in the last 50 years, drug resistance is increasing. Efforts to develop a vaccine have been hampered by antigenic variation, a mechanism that allows African trypanosomes to escape the host’s immune response. Proposed alternative or complementary control strategies are based on limiting the pathology rather than preventing infection. Therefore it seems crucial the identification of new pathogenicity factors that could serve as drug targets is crucial. One such factor might be the enzyme family of sialidases or trans-sialidases expressed by trypanosomes. The insect form of the parasite can survive in the migdut of tsetse-flies thanks to a sialic acid coat on its membrane surface. There is no sialic acid metabolism in these parasites but parasite sialidases and trans-sialidase enzymes ensure the transfer of host sialic acids to the parasite membrane surface. A hallmark of trypanosomiasis in the mammalian host is the occurrence of anemia. Anemia is a consequence of the destruction of senescent or abnormal red blood cells (RBC’s) that takes place in the spleen. Here the membranes of RBCs are probably desialated, which in turn presents a signal that is recognized by spleen macrophages that eliminate RBCs byphagocytosis. In this context, during my PhD project, I have characterized the sialidases and trans-sialidases protein of T. congolense and T. vivax and I have studied their function in the animal pathology (trypanosomiasis). (2) Parasitology: metabolism, epigenetics and non-coding RNA: Trypanosoma brucei is a protozoan that displays a complex life cycle with two fundamentally different hosts: insects and mammals. Its metabolism is able to adapt rapidly when changing host. The trypomastigote form of Trypanosoma brucei (mammalian form) uses D-glucose derived carbon source, which is abundant in the fluids of their vertebrate host. In contrast, the insect vector obtain their energy from L-proline and/or L-glutamine, the prominent constituent of their hemolymph and tissue fluids. Consequently, the procyclic forms of Trypanosoma brucei (insect forms) use L-proline like carbon sources. In contrast ex-vivo, the procyclic form can be preferentially grown in D-glucose rich medium. The metabolic switches of these parasites during host changes are not well understood. In this context, during my first year of my PhD, I have studied the role of several metabolism related genes in the procyclic form by RNAi (e.g glycerol-3-phosphatedehydrogenase mitochondrial (GPDHm) and the beta subunit of F1 ATP synthase complex) in order to better understand the metabolic switches between procyclic and bloodstream form of T. brucei. (3) Cellular biology, Cytoskeleton: Actin cytoskeleton in eukaryotic cells plays a central role in cellular motility, adhesion, contractility, endocytosis and maintaining cell polarity. The main proteins of actin cytoskeleton regulation are RhoGTPases. In endothelial cells it was shown that activation of Cdc42 (RhoGTPase) induces a particular reorganization of the actin cytoskeleton called podosome. Recently, among many podosome components, a GAP protein (GTPase Activating Protein) has been localized in endothelial podosomes. In this context, during my Master project, I have studied the RhoGTPase implication (p190RhoGTPase) in actin cytoskeleton reorganization and podosome formation in endothelial cells.