Exploration of streptococcal carbohydrates for glycoconjugate vaccine development

甲型链球菌是人类独有的病原体，每年在全球造成7亿多例感染病例，50万患者死亡。侵袭性链球菌A分离株抗菌素耐药性增加。必须考虑新的治疗选择，Dorfmueller实验室已经建立了一个功能齐全的糖结合疫苗生产平台，提供了新的机会。该学生将探索一个大肠杆菌生产平台，以测试构建几种带有物种特异性碳水化合物修饰的链球菌蛋白的可行性。该学生将从事分子生物学和生物化学，蛋白质纯化和分析。除了A型链球菌外，许多其他人类和动物链球菌细菌产生相关的碳水化合物，这些碳水化合物尚未作为候选疫苗进行探索。学生的任务是研究在大肠杆菌中设计和构建这些碳水化合物的可行性，并对它们的组成和免疫原性进行表征。学生还将有机会为新一代碳水化合物候选疫苗构建新的“载体”。除了在分子生物学、合成生物学和聚糖生物学方面的专家培训和建议外，学生还将有机会通过不同的渠道交流他们的项目，包括研讨会演讲和公共活动。

Strep A bacteria are human exclusive pathogens that are responsible for more than 700 m cases of infection globally per annum, with > 500,000 patients dying. Antimicrobial resistance increases in invasive Strep A isolates. Novel therapeutic options must be considered and the Dorfmueller laboratory has functionally build a glycoconjugate vaccine production platform that provides novel opportunities. The student will explore an E. coli production platform to test the feasibility to build several streptococcal proteins decorated with a species-specific carbohydrate. The student will be engaged in molecular biology and biochemistry, protein purification and analysis. In addition to Strep A bacteria, many other human and veterinary streptococcal bacteria produce related carbohydrates that are yet to be explored as vaccine candidates. The student will have the task to investigate the feasibility to engineer and build these carbohydrates in E. coli and characterise them for their composition and ability to be immunogenic. The student will also have the opportunity to build novel 'vehicles' for this new generation of carbohydrate vaccine candidates. In addition to expert training and advice in molecular biology, synthetic and glycan biology, the student will have the opportunity to communicate their project via different channels, including seminar presentations and public engagements activities.