Flagella remodelling mechanisms throughout the Leishmania mexicana life cycle

Flagella are highly conserved across eukaryotes and have essential roles in motility and sensing. These organelles are assembled by the bi-directional, intraflagellar transport (IFT) system, where protein trains shuttle cargo to and from the flagellar tip. Flagella have dynamic lengths and morphologies thar vary as they assemble and disassemble throughout the cell cycle. The IFT mechanisms and behaviour need to be altered in order to induce flagella assembly, disassembly and modification. Many studies have focussed on IFT functions during flagella assembly however; there is relatively little known about flagella disassembly and remodelling. As flagella disassembly and remodelling have important roles across eukaryotes including: cell cycle progression, implications in diseases such as cancer, and are required for cellular adaptations to their environment, it is important to fully understand the mechanisms that underlie IFT in disassembly and remodelling. In the proposed study we aim to combine proteomic, molecular and microscopy techniques to define the role of IFT in flagella disassembly and remodelling in the parasite Leishmania mexicana. By utilising the Leishmania parasite as a model, we can monitor IFT throughout its life cycle, especially during transitions when rapid changes in flagellum structure occurs. By describing the role of IFT in flagella disassembly and remodelling, we hope to show key proteins involved in these processes and how they may interact with each other and the flagellum structure. In reaching these objectives it would allow us to build a more comprehensive model of the flagella cycle that encompasses assembly, remodelling and disassembly.

BBSRC Priority Areas: Bioscience for health, world-class underpinning bioscience