Gene regulation in baculovirus-infected insect cells: application in the development of a budded virus-free expression system for the production of VL

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VLP-based vaccines have significant potential to protect people (and animals) from some of the most serious viral diseases. The baculovirus expression system is known for its ability to produce high yields of quality VLPs and this combined with ease of use and scalability has led to many healthcare/biotechnology companies exploring their use in vaccine development. What has proved challenging, however, is the removal of contaminating baculovirus particles and this has added to the costs, complexities and time involved in downstream processing and ultimate successful launch of new vaccines. This project has potential to deliver improvements to the upstream production phase that will negate the need for complex and time consuming downstream processing. The potential impact will be to simplify and reduce the cost of VLP purification that may ultimately result in a more efficient VLP-based vaccine pipeline.This project aims to build on our basic understanding of the regulatory control of the genes involved in baculovirus particle (budded virus, BV) production, which occurs in the late phase of the virus replication cycle. The aim is to enable development of an expression vector system in which BV synthesis can be down regulated during VLP production. The project therefore contains a basic research element: understanding gene regulation in the late phase of the baculovirus replication cycle as pertinent to BV production. But it will also include an industrial element that will use the information to develop a novel expression system in which BV production can be switched off or down-regulated during production-runs to yield VLPs for purification. The collaborating organisation, OET Ltd, has a wealth of experience in developing and commercialising novel baculovirus expression systems but development of a system to knock down BV production requires greater understanding of the gene regulation of BV production so that this can be manipulated and translated into a commercially-viable expression vector. In addition to DTP training, the student will receive specific training in modern bioscience techniques including DNA, RNA and protein analyses, cloning, bioinformatics, light and electron microscopy, virus handling and cell culture. The student will be supported to develop their communication and presentation skills through fortnightly lab meetings, a journal club, seminars and presentations (poster and talks) at scientific meetings. Students are also encouraged to take part in demonstrating to develop teaching skills and to take part in outreach activities through the Brookes Public Engagement Network.In addition, the student will benefit from an opportunity to shadow one of OET's senior scientists conducting contract research to obtain an understanding of the role of contract research in vaccine and other R&D programmes led by many of the UK's and overseas' pharma and biotechnology companies. This will provide an insight into the challenges of moving from early stage R&D into trials and production.