GlycoCell Engineering Biology Mission Hub: Transforming glycan biomanufacture for health

聚糖或糖对生命所有领域的生物过程都有巨大的影响。大多数医学上重要的药物都是糖修饰的，疫苗通常针对致病病原体表面的糖。因此，聚糖在生物学和生物技术中都发挥着关键作用。通过糖工程优化蛋白质中糖的表达和添加，为创造成本更低、更有效的疫苗、开发更好的治疗和诊断方法，以及产生更有效地研究健康和疾病的工具提供了一条重要途径。聚糖很难研究和制造，被认为是“生物学的暗物质”。这需要一种新的方法，通过我们的糖细胞联盟的工程生物学的进步是及时和适当的。糖细胞公司建立在我们的糖技术和工程生物学专业知识以及之前的成功基础上，并希望扩大和部署“糖forge”设施，使其成为英国的国家资产。glyforge结合了高通量自动化，优雅的实验设计和先进的数学方法，以快速工程细胞制造新的聚糖。糖细胞将开发和整合尖端技术，培养当前和下一代的研究人员，吸引产业，并推动与更广泛的研究社区的增值翻译。糖细胞的目标将包括细菌和病毒疫苗，以及用于治疗其他疾病的治疗性蛋白质。疫苗是预防感染的最有效方法，已被证明可减少抗菌素的使用。最成功的抗细菌疫苗是糖缀合物（与蛋白质相连的聚糖），可为所有年龄组提供强大、持久的免疫力。目前的糖结合疫苗生产成本高昂，无法在资源匮乏的环境或兽医中使用。高效生产新型疫苗。我们将针对人类病原体A群链球菌和动物病原体ubercoccus。我们将通过有效表达肺炎链球菌的100种聚糖变体和一种具有尚未确定聚糖结构的新型克希氏菌疫苗来测试糖伪造的局限性。我们将进行模拟大流行“压力测试”，以提供100天的快速流行病应对措施，这对英国的防范工作至关重要。这些疫苗将在定制的大肠杆菌和芽孢杆菌细胞中并行生产，这对疫苗的开发和生产具有多重优势。对于治疗性蛋白，多糖结构可以决定药代动力学、蛋白质周转和功能。大多数治疗性糖蛋白都是在哺乳动物宿主体内制造的，以匹配人类的聚糖结构。这些对文化来说代价高昂，挑战医疗保健预算，限制患者获得治疗。我们将利用glyforge进一步开发细菌和酵母细胞，以生产与人类相关的聚糖作为新的治疗药物。这将包括工程酵母菌酵母细胞能够模仿真菌病原体的糖基化模式，生产新的抗真菌药物。毕赤酵母细胞将用于生产新型病毒疫苗，包括艾滋病毒和乳头瘤病毒。这项工作将得到世界领先的聚糖分析设施的支持。培训和发展当前和下一代的研究人员在英国和超越将是中心的糖细胞，并将深入整合到所有的活动。一个由学术界和工业界合作伙伴领导的工程生物学培训计划将在5年内进行。glycell将由一个经验丰富的管理团队领导，并将由一个国际咨询小组指导，以确保我们的愿景，生产新的基于聚糖的药物，并指导继任计划。

Glycans or sugars have a huge impact on biological processes in all domains of life. Most medically important drugs are glyco-modified and vaccines often target the sugars on the surface of disease-causing pathogens. Hence, glycans play a key role in both biology and biotechnology. Optimising the expression and addition of sugars to proteins through glycoengineering offers an important avenue to creating lower cost, more effective vaccines, developing better therapies and diagnostics, and generating tools to more efficiently study health and disease. Glycans are difficult to study and manufacture and are considered the 'dark matter of biology'. This requires a new approach, and the advancement of Engineering Biology through our GlycoCell consortium is both timely and appropriate.GlycoCell builds on our glycotechnology and Engineering Biology expertise and previous successes with a vision to scale and deploy a 'GlycoForge' facility as a UK national asset. The GlycoForge combines high-throughput automation, elegant experiment design, and advanced mathematical methods to rapidly engineer cells to make new glycans. GlycoCell will develop and integrate cutting-edge technologies, train the current and next generations of researchers, attract industry, and drive value-adding translation with the wider research community. GlycoCell's targets will include bacterial and viral vaccines, as well as therapeutic proteins for treatment of other diseases. Vaccines are the most effective way to prevent infections and proven to reduce antimicrobial usage. The most successful vaccines against bacteria are glycoconjugates (glycans linked to proteins), which provide robust, lasting immunity in all age groups. Current glycoconjugate vaccine manufacture is costly and precludes use in resource poor settings or in veterinary medicine. We will efficiently produce novel vaccines. We will target the human pathogen Group A streptococci and animal pathogen Streptococcus uberis. We will test the limits of the GlycoForges with the efficient expression of 100 glycan variants of Streptococcus pneumoniae and a novel Coxiella vaccine that has an as yet unresolved glycan structure. We will undertake a simulated pandemic 'pressure test' to deliver a 100-day rapid epidemic response that will be important for UK preparedness. These vaccines will be produced in parallel in bespoke E. coli and Bacillus cells which have multiple advantages for vaccine development and manufacture. For therapeutic proteins, the glycan structure can dictate pharmacokinetics, protein turnover, and function. Most therapeutic glycoproteins are manufactured in mammalian hosts to match human glycan structures. These are costly to culture, challenging healthcare budgets and limiting patient access to therapies. We will use the GlycoForge to further develop bacteria and yeast cells to produce human-relevant glycans as novel therapeutics. This will include engineering Saccharomyces yeast cells able to mimic the glycosylation patterns of fungal pathogens, producing novel anti-fungal drugs. Pichia yeast cells will be used to produce novel viral vaccines including HIV and papilloma virus. This work will be supported by a world-leading facilities for analysis of glycans. Training and development of the current and next generations of researchers across the UK and beyond will be central to GlycoCell and will be deeply integrated into all activities. A training program in engineering biology led by both academics and industrial partners will occur over 5 years.GlycoCell will be led by an experienced management team and will be steered by an International Advisory Group to secure our vision to produce novel glycan-based medicines and to guide succession planning.