Membrane remodelling during cell division in the thermoacidiophilic archaeaon Sulfolobus acidocaldarius

在分裂时，细胞膜在形状和脂质组成方面经历快速和大规模的变化。虽然这些变化在许多真核生物和细菌中都有特征，但对于古细菌细胞分裂中膜的作用几乎一无所知。古菌脂质在化学上是独特的，膜对缺乏细胞壁的古菌细胞起着特别关键的结构作用。对于嗜热嗜酸古菌Sulfolobus acidocalarius来说就是这样，这是一种典型的嗜热嗜酸古菌，目前是真核生物在实验上最接近的亲戚。虽然在Sulfolobus中，细胞分裂是由ESCRTIII和Vps4（许多真核生物中催化脱落的蛋白的同源物）的活性驱动的，但ESCRTIII在Sulfolobus中重塑的脂质膜具有独特的化学和组织。与细菌或真核生物的脂质不同，古细菌脂质可以跨越膜形成有效的单层。利用高温活细胞成像、脂质组学和结构研究相结合的方法，我旨在确定古细菌脂膜的特性，这些特性是支持ESCRTIII在古细菌细胞分裂中的功能所必需的。为此，我将：1)在活细胞显微镜下，利用商业上可用的和新合成的脂质探针，创造新的工具来可视化古细菌的膜动力学；2)结合脂质组学、蛋白质组学和显微镜技术，确定细胞分裂过程中脂质和膜特性的时空控制；3)利用结构技术和计算机模拟表征ESCRTIII如何与古细菌膜相互作用。通过了解保守蛋白如何作用于这些不同的膜结构，我们希望揭示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.