An advanced bioreactor facility for automated, industry-aligned production of high-value proteins

重组蛋白的生产是生物学中一个非常重要的领域，目前许多蛋白是在细菌、酵母或哺乳动物细胞中生产的，然后进行纯化，以便详细研究它们的结构和机制。然而，重组蛋白的生产也是生物技术行业的核心部分，因为许多最有效的药物都是抗癌或抗炎抗体、细胞因子、生长激素等生物制药。全球生物制药行业的年产值超过1600亿美元。而且它正在迅速增长。研究新的生物制药药物和表达系统是英国的主要优先事项。许多学术团体与生物技术公司密切合作，开发具有增强特性的新细胞系，但尽管公司使用复杂的设备来培养细胞并大量生产蛋白质，但学术团体很少能获得这样的系统。这意味着在努力方面存在严重的不匹配，学者们开发的细胞生长协议不能简单地被他们的工业合作伙伴采用。相反，必须从头开始开发新的生长和蛋白质表达方案。在这项应用中，我们建议购买AMBR250生物反应器系统，该系统允许高度自动化的细菌或哺乳动物细胞以非常高的密度生长。生物反应器的体积只有100-250毫升，但已经证明结果是高度可扩展的；换句话说，使用该系统开发的生长方案在用于更大的反应堆容器时几乎总是有效的。该系统将安装在一个专门设计的单元中，并用于两大类项目：(I)。致力于生物技术项目的团队将从这些设备中受益，因为他们将能够在模仿行业的条件下进行研究。生物技术项目的目标是生产生物制药等高价值蛋白质。这将促进肯特和其他地方的一些重要项目的进展，这些设备还将用于加强肯特、帝国学院和伦敦大学学院参与的一个新的“全球挑战”研究项目的工作。该项目旨在使东南亚国家能够生产自己的生物药物，其中大多数对绝大多数(90%以上)患者来说太昂贵了。(Ii)。从事需要大量重组蛋白的更基础科学领域的团队将受益，因为ambr250系统可以高密度地生产细胞，目标蛋白的生产浓度通常超过每升培养物1克-这对大多数研究项目来说足够容易。拟议的设施将供申请者使用，并向外部用户提供。这在英国的学术机构中将是独一无二的：伦敦大学学院是唯一一所拥有ambr250系统的大学，外部用户不能使用这一系统。这种设备在学术界存在较少的主要原因是生物反应器的成本，这些生物反应器很昂贵，而且是一次性使用的。为了绕过这个问题并确保向学术界提供，肯特大学承诺提供总计80,000 GB的资金，唯一目的是在设施存在的头四年免费提供生物反应器。这将极大地促进外部用户的使用，我们预计许多集团将能够利用该系统的非凡性能。

The production of recombinant proteins is a critically important area in biology, and many proteins are currently produced in bacterial, yeast or mammalian cells and then purified so that their structures and mechanisms can be studied in detail. However, recombinant protein production is also a central part of the biotechnology industry, because many of the most powerful medicines are 'biopharmaceuticals' such as anti-cancer or anti-inflammatory antibodies, cytokines, growth hormones and others. The worldwide biopharmaceutical industry is valued at over $160 billion p.a. and it is growing rapidly. Research into new biopharmaceutical drugs and expression systems is a major priority in the UK.Many academic groups work closely with Biotechnology companies to develop new cell lines with enhanced properties, but whereas companies use sophisticated equipment to grow cells and produce proteins in large amounts, such systems are rarely available to academic groups. This means that there is a significant mismatch in efforts, and cell growth protocols developed by academics cannot be simply adopted by their industrial partners. Instead, new growth and protein expression protocols have to be developed from scratch. In this application we propose to purchase an ambr250 bioreactor system, which allows highly automated growth of bacterial or mammalian cells at very high density. The bioreactor volumes are only 100-250 ml but it has been shown that the results are highly scalable; in other words, growth protocols developed using this system almost invariably work when used used in much larger reactor vessels. The system will be installed in a purpose-designed unit and used in two broad types of project:(i). Groups working on biotechnology projects, where the aim is to produce high-value proteins such as biopharmaceuticals, will benefit from the equipment because they will be able to carry out research under industry-mimicking conditions. This will enhance progress in a number of important projects at Kent and elsewhere, and the equipment will also be used to enhance work in a new 'Global Challenges' research project involving Kent, Imperial College and University College London. This project aims to enable countries in South East Asia to produce their own biopharmaceuticals, most of which are simply too expensive for the vast majority (over 90%) of patients. (ii). Groups working on more fundamental areas of science, where large quantities of recombinant protein are required, will benefit because the ambr250 system can produce cells at high densities and target proteins are often produced at concentration of over 1 gram per litre of culture - easily enough for most research projects.The proposed facility will be used by the applicants and also made available to external users. It will be unique among academic Institutions in the UK: UCL is the only University in possession of an ambr250 system and this is not available to external users. The primary reason for the low presence of this equipment in academia is the cost of the bioreactors, which are expensive and single-use. To circumvent this problem and ensure availability to the academic community, the University of Kent has committed a total of £80,000 for the sole purpose of providing bioreactors free of charge over the first four years of the facility's existence. This will provide a huge boost to uptake by external users and we predict that many groups will be able to capitalise on the system's exceptional performance.