Membrane remodelling during cell division in the thermoacidiophilic archaeaon Sulfolobus acidocaldarius

在分裂时，细胞膜的形状和脂质成分发生快速和大规模的变化。虽然这些变化已经在一些真核生物和细菌中得到了表征，但几乎没有人知道膜在古细菌细胞分裂中的作用。细胞膜脂质在化学上是不同的，对于缺乏细胞壁的古细菌细胞，细胞膜起着特别关键的结构作用。嗜酸硫化叶菌（Sulfolobus acidocaldarius）就是这种情况，它是一种嗜热嗜酸古菌，是目前实验上最接近真核生物的相对物种。虽然硫化叶菌属的细胞分裂是由ESCRTIII和Vps 4的活性驱动的，ESCRTIII和Vps 4是许多真核生物中催化解离的蛋白质的同源物，但硫化叶菌属中ESCRTIII重塑的脂质膜具有独特的化学和组织。与细菌或真核脂质不同，古细菌脂质可以跨越膜以产生有效的单层。使用高温活细胞成像，lipidomics和结构的研究相结合，我的目标是确定的古菌脂质膜的特性，是必要的支持ESCRTIII功能在古菌细胞分裂。为此，我将：1）在活细胞显微镜中使用市售和新合成的脂质探针创建新工具，用于可视化古细菌的膜动力学; 2）使用脂质组学、蛋白质组学和显微镜的组合来确定细胞分裂期间脂质和膜特性的空间和时间控制; 3）使用结构技术和计算机模拟来表征ESCRTIII如何与古细菌膜相互作用。通过了解保守蛋白质如何作用于这些不同的膜结构，我们希望能够阐明细胞分裂的基本原理以及真核生物相对更复杂的分裂机制的进化。

At division, the cellular membrane undergoes rapid and large-scale changes in shape and lipid composition. While these changes have been characterised in a number of eukaryotes and bacteria, almost nothing is known about the role of the membrane in archaeal cell division. Archaeal lipids are chemically distinct and membranes play an especially critical, structural role for archaeal cells that lack a cell wall. This is the case for Sulfolobus acidocaldarius, a model thermoacidophilic archaeon that is currently the closest experimentally tractable relative of eukaryotes. While cell division in Sulfolobus is driven by the activity of ESCRTIII and Vps4 - homologues of the proteins catalysing abscission in many eukaryotes - the lipid membrane that ESCRTIII remodels in Sulfolobus has a unique chemistry and organisation. Distinct from bacterial or eukaryotic lipids, archaeal lipids can span the membrane to create an effective monolayer. Using a combination of high temperature live-cell imaging, lipidomics and structural studies, I aim to determine the properties of the archaeal lipid membrane that are necessary to support ESCRTIII function in archaeal cell division. To do so I will: 1) create new tools for visualising membrane dynamics in archaea using both commercially available and newly synthesised lipid probes in live cell microscopy; 2) identify the spatial and temporal control of lipids and membrane properties during cell division using a combination of lipidomics, proteomics and microscopy; 3) characterise how ESCRTIII interacts with the archaeal membrane using structural techniques and in silico modelling. Through understanding of how conserved proteins can act on such different membrane architectures we hope to shed some light on fundamental principles of cell division as well as the evolution of the comparatively more complex division machinery of eukaryotes.