Flagella remodelling mechanisms throughout the Leishmania mexicana life cycle

鞭毛在真核生物中是高度保守的，并且在运动和传感中具有重要作用。这些细胞器通过双向鞭毛内转运（IFT）系统组装，其中蛋白质列车将货物穿梭于鞭毛尖端。鞭毛具有动态的长度和形态，它们在整个细胞周期中随着组装和分解而变化。IFT机制和行为需要改变，以诱导鞭毛组装，拆卸和修改。许多研究都集中在鞭毛组装过程中的IFT功能，然而，鞭毛拆卸和重塑知之甚少。由于鞭毛拆卸和重塑在真核生物中具有重要作用，包括：细胞周期进程，癌症等疾病的影响，并且是细胞适应其环境所必需的，因此充分了解IFT在拆卸和重塑中的机制是很重要的。在拟议的研究中，我们的目标是联合收割机蛋白质组学，分子和显微镜技术来确定的作用，IFT鞭毛拆卸和改造的寄生虫墨西哥利什曼原虫。通过利用利什曼原虫作为模型，我们可以在其整个生命周期中监测IFT，特别是在鞭毛结构发生快速变化的过渡期间。通过描述IFT在鞭毛拆卸和重塑中的作用，我们希望展示参与这些过程的关键蛋白质以及它们如何相互作用以及鞭毛结构。在实现这些目标的过程中，它将使我们能够建立一个更全面的鞭毛周期模型，包括组装，重塑和拆卸。BBSRC优先领域：生物科学促进健康，世界级的基础生物科学

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