A dual DLS and SEC-MALS instrumentation to characterize protein oligomerization for structural and mechanistic biology

用于表征结构和机械生物学蛋白质寡聚化的 DLS 和 SEC-MALS 双仪器

• 批准号: BB/V01966X/1
• 负责人: Julien Bergeron
• 金额: $ 26.15万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV01966X%2F1
• 关键词: dual; DLS; SEC; MALS; instrumentation

The physical characterization of proteins is critical for the fundamental understanding of biological processes, as well as for new drug development. In particular, the capacity to determine if proteins naturally assemble, interact with partners (other proteins, nucleic acids, lipids etc.), or is modified by other molecules such as lipids, sugars, etc.., is essential to decipher their function.We seek to acquire a device that exploits how solutions that contain proteins affect laser light, to precisely and accurately determine the "size" (molecular weight) of a protein. This is an essential information to elucidate its mechanism of action, how it interacts with other molecules, etc. In addition, this equipment allows to monitor how proteins stick to each other ("aggregate"), which can happen for their natural function, for example in proteins that forms filaments across the cell to deliver cargo (for example, actin or tubulin), but also can be a sign of pathology (amyloids). In particular, we will use this equipment extensively in our research efforts to understand proteins involved in bacterial virulence and antibiotic resistance, viral pathogenesis (including SARS-CoV-2), cancer and tumor pathogenesis, and neurodegenerative diseases such as Alzheimer's and Parkinson's diseases.

蛋白质的物理特性对于生物过程的基本理解以及新药开发至关重要。特别是，确定蛋白质是否天然组装，与伴侣（其他蛋白质，核酸，脂质等）相互作用，或者被其它分子如脂质、糖等修饰，我们寻求获得一种设备，利用含有蛋白质的溶液如何影响激光，以精确和准确地确定蛋白质的“大小”（分子量）。这是阐明其作用机制的重要信息，它如何与其他分子相互作用等。此外，该设备允许监测蛋白质如何相互粘附（“聚集”），这可能发生在它们的自然功能中，例如在形成纤维的蛋白质中穿过细胞以递送货物（例如，肌动蛋白或微管蛋白），但也可能是病理学（淀粉样蛋白）的标志。特别是，我们将在我们的研究工作中广泛使用这种设备，以了解与细菌毒力和抗生素耐药性、病毒发病机制（包括SARS-CoV-2）、癌症和肿瘤发病机制以及阿尔茨海默病和帕金森病等神经退行性疾病有关的蛋白质。

项目成果

Control of the flagellation pattern in Helicobacter pylori by FlhF and FlhG.

FlhF 和 FlhG 对幽门螺杆菌鞭毛模式的控制。

• DOI: 10.1128/jb.00110-23
• 发表时间: 2023
• 期刊: Journal of bacteriology
• 影响因子: 3.2
• 作者: Gibson,KatherineH;Botting,JackM;Al-Otaibi,Natalie;Maitre,Kriti;Bergeron,Julien;Starai,VincentJ;Hoover,TimothyR
• 通讯作者: Hoover,TimothyR

Oligomerization of the FliF Domains Suggests a Coordinated Assembly of the Bacterial Flagellum MS Ring.

• DOI: 10.3389/fmicb.2021.781960
• 发表时间: 2021
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Mariano G;Faba-Rodriguez R;Bui S;Zhao W;Ross J;Tzokov SB;Bergeron JRC
• 通讯作者: Bergeron JRC