Structural dynamics of Augmin in the creation of microtubule branches. (ref: 4274)

细胞分裂是一个基本的细胞过程，需要精确的成核和组织的蛋白质纤维，微管，成一个有丝分裂纺锤体能够染色体分离。最近发现的保守蛋白复合物“Augmin”提出了如何在空间和时间上控制细胞中有丝分裂微管成核的重大新问题。Augmin是一种8个亚基复合物，负责招募主要的微管成核蛋白-微管蛋白到预先存在的微管中。Wakefield实验室最近在体外重建了该复合物(1)，并在Augmin的结构和拓扑结构方面取得了重大进展(4)，但我们还远远不能理解Augmin在分子水平上的功能。菲利普斯实验室开发了先进的氢/氘交换质谱（HDX-MS）方法，以及新的仪器和软件，精确地分析蛋白质结构动力学。最近，他们用这种方法来观察大型抗体复合物中蛋白质与蛋白质之间的相互作用，并以毫秒级的分辨率来测量蛋白质结构和功能的变化。(2、3)。总之，这两个实验室的综合专业知识提供了一个无与伦比的机会来构建描述Augmin复合体的结构和数学模型，以及它的动态行为如何与支撑细胞分裂的关键功能相关。这个博士项目是一个有抱负的跨学科科学家加入我们研究团队的机会。该项目将适合菲利普斯和韦克菲尔德小组研究活动的核心。该学生将得到这些小组其他成员的支持和协助，包括细胞生物学家、蛋白质工程师和结构质谱专家。学生将学习氢/氘交换质谱，果蝇饲养，细胞培养，生物化学，蛋白质化学，以及熟悉几种编程语言，数学建模和统计技能。

Cell division is a fundamental cellular process, requiring the precise nucleation and organisation of protein fibres, microtubules, into a mitotic spindle capable of chromosome segregation.The recent discovery of the conserved protein complex 'Augmin' poses major new questions of how the mitotic microtubule nucleation is controlled in cells in space and time. Augmin is an eight subunit complex responsible for recruiting the major microtubule nucleator, gamma-tubulin, to pre-existing microtubules. The Wakefield lab have recently have reconstituted the complex in vitro (1) and made significant advances relating to the structure and topology of Augmin (4) but we are far from understanding how Augmin functions at the molecular level.The Phillips lab, have developed cutting-edge hydrogen/deuterium-exchange mass spectrometry (HDX-MS) approaches, together with new instrumentation and software, precisely to analyse protein structural dynamics. Recently, they have used this to visualise protein-protein interactions in large antibody complexes and to measure protein structure:function changes with millisecond time resolution. (2, 3). Together, the combined expertise of these two labs provide an unparalleled opportunity to construct structural and mathematical models describing the Augmin complex and how its dynamic behaviour relates to its crucial function underpinning cell division. This PhD project is an opportunity for an ambitious and interdisciplinary scientist to join our team of researchers. The project will fit at the core of the group research activity of both the Phillips and Wakefield groups. The student will be supported and assisted by other members of these groups, including cell biologists, protein engineers and structural mass spectrometry experts. The student will learn hydrogen/deuterium-exchange mass spectrometry, Drosophila husbandry, cell culture, biochemistry, protein chemistry, plus familiarization with several programming languages, mathematical modelling and statistical skills.