Trypanosomes are flagellated parasites responsible for various tropical diseases, including sleeping sickness in Central Africa caused by Trypanosoma brucei. Trypanosomes also represent exciting model organisms to study as they exhibit unique cellular features and are amenable to modern reverse genetics technology. Our group is interested in two topics: (1) biology and applications of RNA interference and (2) flagellum formation and function.

RNA interference.
RNAi is a sequence-specific RNA destruction process mediated by short or long double-stranded RNA that was discovered in 1998 by C. Mello and A. Fire (Nobel winners 2006). We previously identified a gene essential for RNAi and showed that this process participates to chromosome segregation during mitosis and to control of abundance of transcripts derived from transposable elements (these mobile elements make up 5 % of the trypanosome genome and > 40 % of the human genome). Recently, we demonstrated that RNAi activity was required for the control of expression of some families of pseudogenes (genes that do not code for proteins). Moreover, RNAi acts differently in mitosis and transposon control as a cell line competent for one function but not the other was produced in the laboratory.

Flagellum formation and functions.
The flagellum is a cylindrical organelle made of microtubules and composed of more than 200 proteins. We showed that it is constructed by a specific process called intraflagellar transport and identified a dozen of genes involved in this mechanism. We demonstrated that the flagellum is critical for the trypanosome cell cycle and have characterized its role in cell motility. We have identified more than 50 genes coding for putative flagellar proteins and defined their function after individual silencing by inducible RNAi. Some genes are entirely novel and many are shared with other flagellated eukaryotes. Trypanosomes use several activities of the flagellum for morphogenetic processes such as the definition of cell polarity or organelle positioning.

Trypanosome as a model for genetic diseases. Several genetic diseases are linked to defects in cilia and flagella function. However, mammalian, insect or nematode ciliated cells do not propagate in vitro and are poorly amenable to transfection. Our data reveal that trypanosomes are an excellent model to study genetic diseases related to cilia and flagella defects. Collaborations with several medical groups studying such genetic diseases have been set up and have recently been funded by external grants.