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

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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.