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

Augmin 在微管分支创建中的结构动力学。

• 批准号: 2705205
• 金额: --
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2705205
• 关键词: Structural; dynamics; Augmin; creation; microtubule

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.

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'提出了重大的新问题，有丝分裂微管成核是如何控制在细胞中的空间和时间。Augmin是一种八亚基复合物，负责将主要的微管成核剂γ-微管蛋白募集到预先存在的微管中。韦克菲尔德实验室最近在体外重建了复合物（1），并在Augmin的结构和拓扑结构方面取得了重大进展（4），但我们还远未了解Augmin在分子水平上的功能。菲利普斯实验室开发了尖端的氢/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，他们已经用它来可视化大型抗体复合物中的蛋白质-蛋白质相互作用，并以毫秒级的时间分辨率测量蛋白质结构：功能变化。（2，3）。这两个实验室的专业知识提供了一个无与伦比的机会，可以构建描述Augmin复合物的结构和数学模型，以及其动态行为如何与其支持细胞分裂的关键功能相关。这个博士项目是一个雄心勃勃的跨学科科学家加入我们的研究团队的机会。该项目将适合在核心的小组研究活动的菲利普斯和韦克菲尔德集团。学生将得到这些小组其他成员的支持和帮助，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。