伦敦国王学院CSC-KCL联合奖学金招收2022年细菌结构生物学方向PhD

伦敦国王学院King’s College London牙科系招收2022年细菌结构生物学方向公派PhD

申请人将受邀于2022年10月左右进入伦敦国王学院牙科、口腔和颅面科学学院（2020 QS Dentistry 世界第一）进行牙龈卟啉单胞菌中阴离子脂多糖（A-LPS）的生物合成及其向九型分泌系统（T9SS）货物的附着/组装相关机制的研究。该研究将在Dr. James Garnett和Prof. Mike Curtis实验室（Centre of Host-Microbiome Interaction）展开。申请（King’s）的最终截止日期为2022年1月初（具体请参照King’s Apply的相关声明）。

项目研究背景：牙龈卟啉单胞菌（Porphyromonas gingivalis）是一种革兰氏阴性口腔致病菌，是诱发慢性牙周炎的关键致病菌。该菌利用九型分泌系统（Type-Ⅸ secretion system，T9SS）输出毒力因子，然后通过特定类型的脂多糖（阴离子/A-LPS）共价连接/附着到细胞表面。然而，P. gingivalis中A-LPS的生物合成及其运输到外膜的机制尚不清楚。同样地，A-LPS与T9SS货物蛋白（毒力因子等）之间连接的确切性质也不清楚。

项目总体目标：该博士项目研究的总体目标是从原子层面深入了解A-LPS如何在P. gingivalis周质中形成并运输到外膜，以及在什么阶段、以何种形式附着到T9SS货物蛋白上的。该项目将涉及P. gingivalis的厌氧培养，细菌pull-downs以及突变株构建等。此外还将涉及蛋白在大肠杆菌系统和P. gingivalis菌内的表达纯化，所得蛋白将用于生物物理表征和结构生物学研究分析研究（冷冻电镜，晶体学）。此研究将帮助我们了解/建立T9SS或A-LPS相关的新的生物通路，也可能为开发新的抗菌化合物提供新的药物靶点。

申请者要求：1. 拥有世界一流大学（中国、美国、英国etc.）生物化学、微生物学（或类似）学士学位和硕士学位的中国公民。2. 申请者必须提供精通英语语言技能的证明（具体参考各faculty对于不同专业/学位申请者英语语言能力的要求）。

为了尽早与导师互相讨论项目的更多细节及时完成King’s Apply流程，请于2021年11月19日前邮件联系Dr. James Garnett: james.garnett@kcl.ac.uk

导师信息详见：

https://www.kcl.ac.uk/research/garnett-lab-fodocs

https://www.kcl.ac.uk/people/mike-curtis

**建议：邮件正文请用简洁语言概括自己的专业背景和申请意愿，更多细节请放在个人简历中，切忌冗长。

英文版介绍：

PhD studentship: “Understanding anionic lipopolysaccharide biosynthesis and its attachment to type-IX secretion system cargo in Porphyromonas gingivalis”

Applications are invited for a King’s College London - China Scholarship Council (CSC) joint PhD scholarship starting in October 2022. This work will be carried out in the labs of Dr. James Garnett and Prof. Mike Curtis (Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences), King’s College London. The final deadline for applications will be at the beginning of January 2022.

Porphyromonas gingivalis is a Gram-negative pathogenic bacterium of the oral cavity and causes chronic periodontitis. It uses a type-IX secretion system (T9SS) to export virulence factors, which are then covalently attached to the cell surface via a specific type of liposaccharide (anionic/A-LPS). However, the biosynthesis of A-LPS in P. gingivalis and how it is transported to the outer membrane is unclear. Likewise, the exact nature of A-LPS attachment to T9SS cargo proteins is also vague.

The overall aim of this PhD project is to provide atomic insight into how A-LPS is formed in the P. gingivalis periplasm and then trafficked to the outer membrane, and then at what stage and how A-LPS is attached to T9SS cargo proteins. This project will involve anaerobic culturing of P. gingivalis, performing bacterial pull-downs and creating mutant strains. Proteins will be expressed/purified using Escherichia coli but also isolated directly from P. gingivalis, then used for biophysical characterization and structural biology studies (Cryo-EM, crystallography). Gaining molecular insight here will allow us to understand new biological processes but may also present novel drug targets for developing new antibacterial compounds.

Applications are invited from Chinese Citizens with a BSc and a Master’s degree in Biochemistry, Microbiology (or similar) from a top university anywhere in the world (China, USA, UK etc). Students are required to provide evidence of their proficiency in English language skills. In order to organize prior shortlisting and discuss the project in more detail please contact Dr. James Garnett before 19^th November 2021: james.garnett@kcl.ac.uk

https://www.kcl.ac.uk/research/garnett-lab-fodocs

https://www.kcl.ac.uk/people/mike-curtis

References

Lasica et al. (2017) Front. Cell. Infect. Microbiol. 7, 215.

Rangarajan et al. (2017) J. Bacteriol. 199, e00751-16