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Identification of Bacterial Post-translational Modifications that Regulate Antimicrobial Resistance

调节抗菌素耐药性的细菌翻译后修饰的鉴定

基本信息

批准号：
2091711
负责人：
金额：
--
依托单位：
CARDIFF UNIVERSITY
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2091711
关键词：
Identification Bacterial Post translational Modifications

项目摘要

This PhD project aims to identify protein post-translational modifications that regulate antimicrobial resistance of bacteria. Drug-resistant bacteria kill over 700,000 people a year worldwide and have become serious threats to global healthcare systems. If we leave the problem of antimicrobial resistance unattended, the annual death toll could rise to 10 million by 2050. Thus, there is a clear need to understand the regulatory mechanisms of antimicrobial resistance as it will facilitate development of new therapeutics against bacterial infection. Post-translational modifications can confer novel properties to the modified proteins, including changes in protein activity, subcellular localisation, interaction partners, and stability. Recent advances in proteomics have revealed that a wide range of bacterial proteins, including those relevant to drug resistance, are subjected to different post-translational modifications. However, the functional significance of these identified post-translational modifications remains largely unknown. To address this problem, we will apply techniques in different disciplines, including: Analytical science (to identify post-translational modifications uniquely present in drug-resistant bacteria). Synthetic biology (using genetic code expansion to incorporate amino acids with post-translational modifications). Chemical biology (to characterise the functions of specific post-translational modification in biochemical assays and bacterial cells). Our studies will likely reveal new therapeutic targets against bacterial infections, setting the corner stone for subsequent drug discovery research.

该博士项目旨在确定调节细菌抗菌素耐药性的蛋白质翻译后修饰。耐药细菌每年在全球造成70多万人死亡，已成为全球医疗保健系统的严重威胁。如果我们对抗菌素耐药性问题置之不理，到2050年，每年的死亡人数可能会上升到1 000万。因此，有一个明确的需要，了解抗菌素耐药性的调控机制，因为它将有助于开发新的治疗细菌感染。翻译后修饰可以赋予修饰的蛋白质新的性质，包括蛋白质活性、亚细胞定位、相互作用伴侣和稳定性的变化。蛋白质组学的最新进展揭示了广泛的细菌蛋白质，包括与耐药性相关的蛋白质，受到不同的翻译后修饰。然而，这些鉴定的翻译后修饰的功能意义在很大程度上仍然未知。为了解决这个问题，我们将应用不同学科的技术，包括：分析科学（以确定耐药细菌中独特的翻译后修饰）。合成生物学（使用遗传密码扩展来整合具有翻译后修饰的氨基酸）。化学生物学（在生化分析和细菌细胞中验证特定翻译后修饰的功能）。我们的研究可能会揭示针对细菌感染的新治疗靶点，为后续药物发现研究奠定基础。